News

News, Press Release Nicole Johnson News, Press Release Nicole Johnson

Charles River Collaborates with Patient Advocacy Group, FOXG1 Research Foundation to Advance Rare Disease Gene Therapy Development

WILMINGTON, Mass.--(BUSINESS WIRE)--Jul. 30, 2024-- Charles River Laboratories International, Inc. (NYSE: CRL) announced today a collaboration with the FOXG1 Research Foundation (FRF) highlighting the patient advocacy group’s model to independently drive drug development through the clinical phase. The parent-led global organization driving the research to cure FOXG1 syndrome and related neurological disorders will collaborate with Charles River in a comprehensive gene therapy contract development and manufacturing organization (CDMO) agreement.

“Charles River is proud to work with the FOXG1 Research Foundation to advance its gene-therapy through clinical trials,” said Kerstin Dolph, Corporate Senior Vice President, Global Manufacturing, Charles River. “The FOXG1 patient population has an incredible unmet need, and we are looking forward to lending our expertise to FRF as they continue to trailblaze a path toward providing rare disease treatments.

Clinical trials for AAV9 gene therapy bolstered with plasmid and viral vector CDMO expertise

WILMINGTON, Mass.--(BUSINESS WIRE)--Jul. 30, 2024-- Charles River Laboratories International, Inc. (NYSE: CRL) announced today a collaboration with the FOXG1 Research Foundation (FRF) highlighting the patient advocacy group’s model to independently drive drug development through the clinical phase. The parent-led global organization driving the research to cure FOXG1 syndrome and related neurological disorders will collaborate with Charles River in a comprehensive gene therapy contract development and manufacturing organization (CDMO) agreement.

“Charles River is proud to work with the FOXG1 Research Foundation to advance its gene-therapy through clinical trials,” said Kerstin Dolph, Corporate Senior Vice President, Global Manufacturing, Charles River. “The FOXG1 patient population has an incredible unmet need, and we are looking forward to lending our expertise to FRF as they continue to trailblaze a path toward providing rare disease treatments.”

Through the collaboration, Charles River will provide FRF with access to extensive cell and gene therapy expertise and generate materials for FRF’s Phase I-II adeno-associated viral (AAV) vector-based gene therapy clinical trials at its plasmid DNA and viral vector CDMO centers of excellence (CoE). The established CDMO will supply phase-appropriate High Quality (HQ) plasmid starting materials manufactured at its Alderley Park CoE in addition to good manufacturing practice (GMP) AAV9 viral vector manufactured at its Rockville CoE, leveraging an integrated manufacturing and biologics testing portfolio to streamline their path to the clinic.

“Given the limited investment for rare disease groups like ours, our foundation has created a model that allows us and other patient advocacy groups to operate like a virtual biotech company and independently and efficiently drive drug development,” said Nasha Fitter, FOXG1 Parent, Co-founder and Chief Executive Officer, FOXG1 Research Foundation.

A New Approach to Drive Rare Disease Drug Development

Founded in 2017 and propelled by innovation and an urgency to accelerate the road to therapeutics for FOXG1 syndrome, FRF has created a replicable model for rare disease patient advocacy groups to take control and drive the development of treatments when no options exist. This includes pioneering novel AI platforms for patient data and streamlining preclinical work.

“The success of FRF’s model is not only focused on operating as a highly efficient team, but also partnering with organizations that are equally passionate about bringing treatments to children with the highest unmet need and severe burden of disease. Selecting the right partner is critical and Charles River has demonstrated a deep understanding of our model and commitment to working on our therapies,” continued Fitter.

FOXG1 syndrome is a severe rare neurological genetic disorder that greatly impacts early brain development and typically causes epilepsy and a host of medical complexities and disabilities. There are approximately 1,000 patients diagnosed with FOXG1 syndrome worldwide, with the diagnosis rate climbing steadily year-over-year and no approved treatments. Most children with FOXG1 syndrome cannot walk or talk or take care of their basic needs.

Cell and Gene Therapy CDMO Solutions

In recent years, Charles River has significantly broadened its cell and gene therapy portfolio with several acquisition integrations and expansions to simplify complex supply chains and meet growing demand for plasmid DNA, viral vector, and cell therapy services. Combined with the Company’s legacy testing capabilities, Charles River offers an industry-leading “concept to cure” advanced therapies solution.

Presented live at the Charles River Cell and Gene Therapy Summit, March 19, 2024, in San Francisco, watch Nasha Fitter’s FOXG1 Research Foundation Patient Story session on-demand, and explore the Summit resource hub: https://bit.ly/4bb2uDu

Also, listen to "A Mom’s Mission", a Vital Science Podcast, broadcast July 16, 2024, where Nasha discusses the origins of FOXG1 Research Foundation, how daughter Amara’s life has been shaped by her diagnosis, and how collaboration has helped advance their mission: https://bit.ly /3LuCpog

About Charles River

Charles River provides essential products and services to help pharmaceutical and biotechnology companies, government agencies and leading academic institutions around the globe accelerate their research and drug development efforts. Our dedicated employees are focused on providing clients with exactly what they need to improve and expedite the discovery, early-stage development and safe manufacture of new therapies for the patients who need them. To learn more about our unique portfolio and breadth of services, visit www.criver.com.

About FOXG1 Research Foundation

The FOXG1 Research Foundation (FRF) is the global, parent-led rare disease patient organization dedicated to advancing treatments for FOXG1 syndrome and related disorders, while advocating for and supporting patients and families worldwide. FOXG1 syndrome is a rare neurological developmental disorder linked to Autism Spectrum Disorder, epilepsy, and developmental disabilities. Founded in 2017, FRF has rapidly emerged as a leader and innovator in the rare disease patient advocacy space, developing novel platforms and an efficient blueprint to accelerate drug development for rare diseases. As a Chan Zuckerberg Initiative partner and recognized through its CEO’s presentation at the inaugural White House Rare Disease Forum, FRF is committed to radically improving the landscape for the 300 million patients affected by rare diseases worldwide.

www.foxg1research.org

View source version on businesswire.com: https://www.businesswire.com/news/home/20240730710706/en/

Charles River Investor Contact:

Todd Spencer
Corporate Vice President, Investor Relations 781.222.6455 [email protected]

Charles River Media Contact:

Amy Cianciaruso
Corporate Vice President, Chief Communications Officer 781.222.6168 [email protected]

FOXG1 Research Foundation Media Contact:

Nicole Johnson
Co-Founder and Executive Director [email protected]

Source: Charles River Laboratories International, Inc.

Read More
News, Publication Nicole Johnson News, Publication Nicole Johnson

New publication shows groundbreaking results in FOXG1 AAV9 gene therapy studies; rescuing structural brain abnormalities

Groundbreaking Study Shows Promise in AAV9 Gene Therapy for FOXG1 Syndrome; Rescue of Brain Structure Abnormalities and Deficits.

[Buffalo, New York June 10, 2024] – A landmark study led by Dr. Soo-Kyung Lee, Chief Scientific Officer at the FOXG1 Research Foundation and Empire Innovation Professor and Om P. Bahl Endowed Professor in the Department of Biological Sciences at University at Buffalo, and Dr. Jae Lee, Professor in the Department of Biological Sciences at University at Buffalo, in collaboration with Dr. Kathrin Meyer (responsible for the SMA gene therapy), has been published in Molecular Therapy Methods & Clinical Development.

PRESS RELEASE

Groundbreaking Study Shows Promise in AAV9 Gene Therapy for FOXG1 Syndrome; Rescue of Brain Structure Abnormalities and Deficits.

[Buffalo, New York June 10, 2024] – A landmark study led by Dr. Soo-Kyung Lee, Chief Scientific Officer at the FOXG1 Research Foundation and Empire Innovation Professor and Om P. Bahl Endowed Professor in the Department of Biological Sciences at University at Buffalo, and Dr. Jae Lee, Professor in the Department of Biological Sciences at University at Buffalo, in collaboration with Dr. Kathrin Meyer (responsible for the SMA gene therapy), has been published in Molecular Therapy Methods & Clinical Development.

The paper, titled "The postnatal injection of AAV9-FOXG1 rescues corpus callosum agenesis and other brain deficits in the mouse model of FOXG1 syndrome," presents novel findings that have significant implications for treating FOXG1 syndrome, a severe neurodevelopmental disorder characterized by profound brain structure abnormalities.

The study explores the therapeutic potential of adeno-associated virus 9 (AAV9) mediated delivery of the FOXG1 gene. Remarkably, intracerebroventricular injection of AAV9-FOXG1 in a Foxg1 heterozygous mouse model ‘postnatally’ demonstrated the rescue of a wide range of brain pathologies including the amelioration of corpus callosum deficiencies, restoration of dentate gyrus morphology in the hippocampus, normalization of oligodendrocyte lineage cell numbers, and rectification of myelination anomalies.

"Our findings highlight the efficacy of AAV9-based gene therapy as a viable treatment strategy for FOXG1 syndrome and potentially other neurodevelopmental disorders with similar brain malformations," said Dr. Jae Lee. "This research asserts the therapeutic relevance of our approach in postnatal stages, which is a critical time frame for intervention."

Dr. Soo-Kyung Lee commented, 'We are thrilled by the full rescue of brain structure abnormalities observed in our mouse model through this study. It marks a significant step forward in our research. With these promising results, we are eager to advance this AAV9 gene therapy towards human clinical trials, hopeful that we can extend these breakthroughs to benefit children with FOXG1 syndrome.

This pioneering work provides a solid foundation for advancing this gene therapy towards human clinical trials, aiming to offer a transformative impact on the lives of patients with FOXG1 syndrome.

The FOXG1 Research Foundation continues to lead the way in innovative research for rare neurodevelopmental disorders, emphasizing the urgency and potential of cutting-edge treatments to alter the course of these conditions fundamentally.

Find the Molecular Therapy Methods & Clinical Development FOXG1 Paper HERE

Find FOXG1 Key Papers HERE

Contact: [email protected]

FOXG1 AAV9- Gene Therapy Data from FOXG1 Research Center at UB | Graphic Abstract

Learn more about The FOXG1 Research Center at the University at Buffalo

Read More
News, YouTube, Announcement Nicole Johnson News, YouTube, Announcement Nicole Johnson

FOXG1 Research Foundation's Nasha Fitter Speaks At The White House Rare Disease Forum

FOXG1 Research Foundation Co-founder and CEO Nasha Fitter was the first spotlight speaker at the White House Rare Disease Forum hosted by the White House Office of Science and Technology Policy's Health Outcomes Team February 28th ahead of Rare Disease Day 2024.

FOXG1 Research Foundation Co-founder and CEO Nasha Fitter was the first spotlight speaker at the White House Rare Disease Forum hosted by the White House Office of Science and Technology Policy's Health Outcomes Team February 28th ahead of Rare Disease Day 2024.

Nasha Fitter represented the FOXG1 syndrome community as well as the 30 million patients, 15 million children, in the United States living with a rare disease. Nasha spoke about radical funding changes required to support drug development uniquely led by patient organization groups like the FOXG1 Research Foundation.

Following Nasha’s clear and impactful presentation, following speakers from ARPA-H, the Chan Zuckerberg Initiative, and Global Genes cited Nasha’s speech and the work of the FOXG1 Research Foundation to show how efficiently patient organizations can drive drug development if given funding.

Thank you to the White House for giving this platform, listening, and considering how far government funds can go to saving lives and alleviating significant economic burden if distributed among the patient organizations that are swiftly driving drug development because it is their children’s lives at stake

FOXG1 Research Foundation CEO and co-founder Nasha Fitter speaks at the first White House Rare Disease Forum

Nasha’s speech has sparked a conversation throughout the rare disease space.

See Nash’s LinkedIn follow up of the forum …

FOXG1 Research Foundation co-founder Nasha Fitter is a spotlight speaker at the White House Rare Disease Forum 2024

On Wednesday, February 28, as part of the Biden-Harris Administration’s goal to improve health outcomes, the White House Office of Science and Technology Policy will host a forum marking Rare Disease Day and highlighting the Biden-Harris Administration’s commitment to supporting patients and families facing a rare disease and delivering progress against the nearly 10,000 known rare diseases that impact up to 30 million Americans.
 
Leaders from the Biden-Harris Administration and the private and nonprofit sectors will work together to:

  • Elevate the experiences and expertise of people and families facing rare diseases;

  • Share developments from the Biden-Harris Administration and rare disease community and learn from one another to accelerate progress; and

  • Identify opportunities to improve rare disease diagnosis, advance research and access to innovation to deliver effective treatment, and boost support for patients and families.

WHEN: Wednesday, February 28, 5:30 PM – 7:00 PM ET
WHERE: The event will be livestreamed at https://youtube.com/live/uG43oLZzeBE
FEATURED SPEAKERS

  • Dr. Arati Prabhakar, Assistant to the President for Science and Technology, Director of the White House Office of Science and Technology Policy

  • Dr. Danielle Carnival, Deputy Assistant to the President for the Cancer Moonshot, Deputy Director for Health Outcomes, White House Office of Science and Technology Policy

  • Dr. Monica Bertagnolli, Director, National Institutes of Health

  • Dr. Renee Wegryzn, Director, Advanced Research Projects Agency for Health

  • Nasha Fitter, Co-founder, FOXG1 Research Foundation

  • Emily Kramer-Golinkoff, Co-founder, Emily’s Entourage

  • Dr. David Fajgenbaum, Co-founder, Every Cure

  • Shonta Chambers, Executive Vice President-Health Equity Initiatives and Community Engagement at Patient Advocate Foundation

  • Dr. Joni Rutter, Director, National Center for Advancing Translational Sciences

  • Tamar Thompson, Vice President, Head of Global Corporate Affairs, Alexion, AstraZeneca Rare Disease

  • Dr. Edward Neilan, Chief Medical and Scientific Officer, National Organization for Rare Diseases

  • Charlene Son Rigby, Chief Executive Officer, Global Genes

  • Tania Simoncelli, Vice President, Science and Society, Chan Zuckerberg Initiative

  • Julia Tierney, Deputy Center Director (Strategy, Policy & Legislation), Center for Biologics Evaluation & Research, Food and Drug Administration

  • Paul Melmeyer, Vice President, Public Policy and Advocacy, at the Muscular Dystrophy Association

  • Kim McClellan, President of the Recurrent Respiratory Papillomatosis Foundation

  • Annie Kennedy, Chief of Policy, Advocacy, and Patient Engagement, EveryLife Foundation

CONTACT: For press inquiries related to this event please email [email protected].
 
BACKGROUND: The Orphan Drug Act defines a rare disease as a disease or condition that affects fewer than 200,000 people. In the United States, rare diseases affect more than 30 million people in total. Of nearly 10,000 known rare diseases, only 5% have a Food and Drug Administration-approved treatment option.
Recent scientific and technological advancements have provided hope for understanding and delivery of new treatments for rare diseases, but significant work remains to address this critical public health issue that effects about 1 in 10 Americans.

 

Read More
News, Announcement Nicole Johnson News, Announcement Nicole Johnson

FOXG1's Nasha Fitter to Speak at The White House Rare Disease Forum for Rare Disease Day 2024

FOXG1 Research Foundation’s Nasha Fitter is a featured speaker at the White House Rare Disease Forum hosted by the The White House Office of Science and Technology Policy. the White House Office of Science and Technology Policy will host a forum marking Rare Disease Day and highlighting the Biden-Harris Administration’s commitment to supporting patients and families facing a rare disease and delivering progress against the nearly 10,000 known rare diseases that impact up to 30 million Americans. Nasha Fitter will be speaking about the issues with rare disease drug development and share her personal story about her daughter with FOXG1 syndrome.

FOXG1 Research Foundation at the White House Rare Disease Forum

On Wednesday, February 28, as part of the Biden-Harris Administration’s goal to improve health outcomes, the White House Office of Science and Technology Policy will host a forum marking Rare Disease Day and highlighting the Biden-Harris Administration’s commitment to supporting patients and families facing a rare disease and delivering progress against the nearly 10,000 known rare diseases that impact up to 30 million Americans.

Leaders from the Biden-Harris Administration and the private and nonprofit sectors will work together to:

  • Elevate the experiences and expertise of people and families facing rare diseases;

  • Share developments from the Biden-Harris Administration and rare disease community and learn from one another to accelerate progress;

  • and Identify opportunities to improve rare disease diagnosis, advance research and access to innovation to deliver effective treatment, and boost support for patients and families.

WHEN: Wednesday, February 28, 5:30 PM – 7:00 PM ET
WHERE: The White House - The event will be live streamed

FEATURED SPEAKERS

  • Dr. Arati Prabhakar, Assistant to the President for Science and Technology, Director of the White House Office of Science and Technology Policy

  • Dr. Danielle Carnival, Deputy Assistant to the President for the Cancer Moonshot, Deputy Director for Health Outcomes, White House Office of Science and Technology Policy

  • Dr. Monica Bertagnolli, Director, National Institutes of Health

  • Dr. Renee Wegryzn, Director, Advanced Research Projects Agency for Health

  • Nasha Fitter, Co-founder, FOXG1 Research Foundation

  • Emily Kramer-Golinkoff, Co-founder, Emily’s Entourage

  • Dr. David Fajgenbaum, Co-founder, Every Cure

  • Shonta Chambers, Executive Vice President-Health Equity Initiatives and Community Engagement at Patient Advocate Foundation

  • Dr. Joni Rutter, Director, National Center for Advancing Translational Sciences

  • Tamar Thompson, Vice President, Head of Global Corporate Affairs, Alexion, AstraZeneca Rare Disease

  • Dr. Edward Neilan, Chief Medical and Scientific Officer, National Organization for Rare Diseases

  • Charlene Son Rigby, Chief Executive Officer, Global Genes

  • Tania Simoncelli, Vice President, Science and Society, Chan Zuckerberg Initiative

  • Julia Tierney, Deputy Center Director (Strategy, Policy & Legislation), Center for Biologics Evaluation & Research, Food and Drug Administration

  • Paul Melmeyer, Vice President, Public Policy and Advocacy, at the Muscular Dystrophy Association

  • Kim McClellan, President of the Recurrent Respiratory Papillomatosis Foundation

  • Annie Kennedy, Chief of Policy, Advocacy, and Patient Engagement, EveryLife Foundation

CONTACT:

For White House press inquiries related to this event please email [email protected]

For FOXG1 Research Foundation press inquiries email [email protected]
 
BACKGROUND: The Orphan Drug Act defines a rare disease as a disease or condition that affects fewer than 200,000 people. In the United States, rare diseases affect more than 30 million people in total. Of nearly 10,000 known rare diseases, only 5% have a Food and Drug Administration-approved treatment option.
Recent scientific and technological advancements have provided hope for understanding and delivery of new treatments for rare diseases, but significant work remains to address this critical public health issue that effects about 1 in 10 America

Read More
Announcement, News Nicole Johnson Announcement, News Nicole Johnson

University at Buffalo launches center to find treatments for FOXG1 syndrome

University at Buffalo announces the launch of the FOXG1 Research Center to study FOXG1 syndrome’s impact on brain development and translate research to treatments for FOXG1 syndrome. The FOXG1 Research Center will be led by leading experts Soo-Kyung and Jae Lee, whose own daughter has FOXG1 syndrome.

“This center will make UB the home of the world’s premier research center devoted to the studies of FOXG1 syndrome, as well as provide our campus with a new neurodevelopmental biology training program and numerous research funding opportunities,” says Soo-Kyung Lee, PhD, Empire Innovation Professor and Om P. Bahl Endowed Professor in the UB Department of Biological Sciences, who will serve as the FRC’s inaugural director as well as the Chief Scientific Officer of the FOXG1 Research Foundation.

Research will be led by biologists Soo-Kyung and Jae Lee, whose daughter has the rare neurological disorder, FOXG1 syndrome

FOXG1 Research Center at the University at Buffalo is led by Biologists and FOXG1 parents Dr. Soo-Kyung lee and Dr. Jae Lee

By Tom Dinki

Release Date: January 17, 2024

BUFFALO, N.Y. — University at Buffalo biologists Soo-Kyung and Jae Lee were already studying genetics and brain development when their daughter, Yuna, was born with a rare neurological disorder caused by a mutation of the FOXG1 gene.

So the Lees are well positioned — and motivated — to lead a research center dedicated to FOXG1.

UB’s new FOXG1 Research Center (FRC), set to launch in the coming months, aims to translate new discoveries from the lab to clinical trials and, ultimately, develop a cure for FOXG1 syndrome, as well as related autism spectrum disorder.

The FRC will be supported by the FOXG1 Research Foundation (FRF), as well as UB's College of Arts and Sciences and Office of the Vice President for Research and Economic Development. 

“This center will make UB the home of the world’s premier research center devoted to the studies of FOXG1 syndrome, as well as provide our campus with a new neurodevelopmental biology training program and numerous research funding opportunities,” says Soo-Kyung Lee, PhD, Empire Innovation Professor and Om P. Bahl Endowed Professor in the UB Department of Biological Sciences, who is currently FRF’s chief scientific officer and will serve as the FRC’s inaugural director. “The FRC will harness the expertise of our faculty to unravel the remaining mysteries of FOXG1 syndrome and, hopefully, help Yuna and the other children impacted by this disorder.”

The FOXG1 gene is one of the most important genes for early brain development. A master regulator gene, FOXG1 carries the instructions for making a protein called forkhead box G1 that regulates the activity of other genes, many of which are crucial for cellular connectivity and communication. Impairment of FOXG1 causes cognitive and physical disabilities as well as life-threatening seizures. 

There are only about 1,000 known patients diagnosed with FOXG1 syndrome worldwide, according to the FOXG1 Research Foundation. However, the FOXG1 gene has been linked to autism, Alzheimer’s disease and schizophrenia, suggesting that therapy development may be transferable to more common disorders.

There has also been a national push to better study and raise awareness for rare diseases, like FOXG1 syndrome. Last year, the Biden administration established the Advanced Research Projects Agency for Health (ARPA-H) within the National Institutes of Health, whose mission includes treating rare disorders.

The Lees, who joined UB in 2019, have established themselves as leading experts on FOXG1 syndrome since Yuna, now 14, was diagnosed with the disease at the age of 2. Their research has found that the FOXG1 gene and protein remain active in mice after birth, providing hope that some symptoms can be alleviated.

“Although we cannot go back and undo the damage to people who have FOXG1 syndrome, we may be able to modify the effects of the disease and increase their quality of life,” says Jae Lee, PhD, professor of biological sciences. 

They’ve recently had success in this area. Mice who began receiving the Lees’ viral gene therapy a day after their birth saw some functions restored. Soo-Kyung Lee received a $1.5 million grant from the Simons Foundation Autism Research Initiative earlier this year to continue the research.

Planned research topics for the FRC include drug discovery, sensory issues like sleep disturbance and mood changes, and the role of mitochondria in neurodevelopmental disorders.

Joining the Lees at the FRC will be an interdisciplinary team of UB faculty, including expected new hires. Collaborators already in place include:  

  • Denise Ferkey, PhD, associate professor and associate chair of the Department of Biological Sciences;

  • Michael Yu, PhD, associate professor of biological sciences; 

  • Wei Sun, PhD, associate professor and director of undergraduate studies of the Department of Communicative Disorders and Sciences; 

  • Priya Banerjee, PhD, associate professor of physics; 

  • Yungki Park, PhD, associate professor of biochemistry; 

  • Edward Kwon, DDS and PhD, assistant professor of oral biology.  

Graduate students are also expected to conduct research in FRC labs.

“The FRC will harness the expertise of our faculty to unravel the remaining mysteries of FOXG1 syndrome and, hopefully, help Yuna and the other children impacted by this disorder. ”

Soo-Kyung Lee, Empire Innovation Professor and Om P. Bahl Endowed Professor of Biological Sciences

University at Buffalo

Media Contact Information

Tom Dinki
News Content Manager
Physical sciences, economic development
Tel: 716-645-4584
[email protected]

The FOXG1 Research Center at the University at Buffalo led by FOXG1 parents Dr. Soo-Kyung Lee and Dr. Jae Lee, along with FOXG1 Research Foundation, co-founder Nicole Johnson, Chief Drug Development Officer Dr. Gai Ayalon, and FOXG1 grandparents Tom and Janet Horton

Read More
News Nicole Johnson News Nicole Johnson

FOXG1 Research Foundation July Newsletter

FOXG1 Research Foundation July Newsletter 2023!

As we've reached the midway point of 2023, we want to take a moment to provide you with an update on our progress, share some exciting news, and express our heartfelt gratitude for your support in our mission to cure FOXG1 syndrome and related neurological disorders.

First and foremost, we are immensely proud to report that we are well on track to achieve our goals for the year. This progress would not have been possible without the continued dedication and encouragement from supporters like you.

On the research front, we have made significant strides in our gene therapy and antisense programs. Encouragingly, both of these initiatives have yielded promising results in our preclinical models. Additionally, we have identified key pathways that can be targeted by FDA-approved drugs, offering potential avenues to alleviate major symptoms. The screening of several hundred FDA-approved drugs on our zebrafish models has opened up new possibilities for future treatments.

A major breakthrough in our efforts is a new publication from our FOXG1 Patient Registry, which is the most comprehensive data on FOXG1 syndrome in patients to date. This invaluable information is instrumental in ensuring our preparedness for clinical trials, bringing us closer to the day when effective treatments can be made accessible to those in need.

As we continue our relentless work with utmost efficiency and diligence, we cannot ignore the heartache we have experienced in losing too many FOXG1 children this year and over the years. Their memory drives us forward, reinforcing the critical nature of our mission to make a difference in the lives of those affected by this devastating condition.

It is with the deepest conviction that we firmly believe, together, we can provide every FOXG1 child in the world with a life free from suffering. Your support has been an integral part of this collective effort, and for that, we extend our heartfelt gratitude.

Thank you for standing with us on this challenging, but immensely rewarding journey. We are confident that brighter days lie ahead for all those affected by FOXG1 syndrome.

Congratulations and thank you to our Director of Clinical Research, Elli Brimble and our esteemed team of Key Opinion Leaders. This publication marks a major milestone in the work to deeply understand the phenotypes of patients with FOXG1 syndrome so that we can target the most effective therapies.

A special thank you to every FOXG1 parent and caregiver who registered their child and who lives this challenging life every day. 

Read FOXG1 KEY PAPERS HERE     |     Register Your FOXG1 Child HERE

After learning about the success of the new anti-epilepsy drug, Fintepla in other rare disease epilepsy clinical trials, we began working with NYU and Zogenix (Now UCB) to launch a clinical trial for FOXG1 patients. It was important for us to make this an open trial with a remote option so that FOXG1 patients do not have to travel to NYC to participate
This will be the first of many clinical trials designed to help all of our children live easier, healthier lives.  
Learn More HERE. 

Our lead scientists and parents to Yuna, Dr. Soo-Kyung Lee and Dr. Jae Lee, who run the The FOXG1 Center of Excellence at UB have been awarded $1.5 million from The Simons Foundation Autism Research Initiative for our FOXG1 gene therapy work!

Did you know that FOXG1 is an autism-related gene and the work we're doing has a great potential to help solve autism?

We are extremely lucky to have the Lee's working nonstop to find a cure for FOXG1 syndrome. The combination of being brilliant scientists as well as FOXG1 parents make their determination and devotion to finding a cure unparalleled in the field.

This grant is a great help towards our $20M fundraising goal for our promising FOXG1 gene therapy program.  

Continue reading the July newsletter HERE

Read More
News Nicole Johnson News Nicole Johnson

New Children's Book and Digital Platform "Joyfully Josie" Aims to Spark Conversations Around Disabilities, Rare Diseases, and Inclusion

Nicole Zeitzer Johnson announced today the release of her debut book, "Joyfully Josie." Designed to help parents and families discuss inclusion in the context of disabilities, this captivating children's book series aims to foster understanding of rare diseases and the experiences of medically complex individuals.


NEW YORK, June 7, 2023 /PRNewswire/ -- Nicole Zeitzer Johnson announced today the release of her debut book, "Joyfully Josie." Designed to help parents and families discuss inclusion in the context of disabilities, this captivating children's book series aims to foster understanding of rare diseases and the experiences of medically complex individuals.

As the co-founder of the FOXG1 Research Foundation and mother to Josie, who suffers with FOXG1 syndrome, a rare genetic neurodevelopmental disorder, Zeitzer Johnson brings her personal journey and expertise to the pages of "Joyfully Josie." Through the power of storytelling, she enlightens both parents and children, helping them feel comfortable with those who are different.

"Joyfully Josie" is a heartwarming tale that showcases Josie's unwavering spirit and her ability to spread joy to everyone she encounters, despite her many challenges.

"My goal is to help give parents the tools to introduce disabilities and inclusion to their children at a young age. Children are often afraid when they see Josie because they don't understand disabilities or medical complexities. It's intimidating. I hope "Joyfully Josie" will turn their fear into excitement to meet any child with disabilities." Zeitzer Johnson said.

"Joyfully Josie" extends beyond the pages of the book with an innovative interactive digital platform. Through this platform, children can play Josie's favorite games and become a character in Josie's playground, immersing themselves in her world and joining her mission to find a cure for FOXG1 syndrome and childhood neurological diseases. This unique blend of storytelling and interactivity creates an engaging learning experience that empowers children to make a difference.

Nicole Zeitzer Johnson's dedication to promoting awareness and finding a cure for rare diseases is exemplified by her work with the FOXG1 Research Foundation. As one of the fastest-growing rare disease patient organizations and a Chan Zuckerberg Initiative "Rare As One" partner, the foundation has made significant strides in advancing research, raising awareness, and supporting affected families. Through "Joyfully Josie," Nicole continues to champion the cause, using her platform to create positive change in the lives of countless individuals and families. All profits from book sales go directly to the FOXG1 Research Foundation.

"Joyfully Josie" is available to purchase at www.joyfullyjosie.love and multiple retailers including, Amazon. Retailers contact [email protected] for information.

About Nicole Zeitzer Johnson:
Nicole Zeitzer Johnson is an inspirational leader who co-founded the FOXG1 Research Foundation, known for its innovative approaches in the field of rare diseases. With her personal experience as a mother to Josie, who was born with FOXG1 syndrome, a severe rare neurological disease, Nicole brings a deep understanding and passion to her work. Leveraging nearly three decades of experience in media and entrepreneurship, she leads the foundation in pioneering initiatives that aim to bring successful therapeutics, including gene therapy, to clinical trials in the near future.

In June 2023, Nicole launched "Joyfully Josie," a groundbreaking children's book series and digital platform. This project not only serves as a testament to her dedication to raising awareness about disabilities and rare diseases but also offers parents a valuable tool to teach their children about empathy, understanding, and inclusion from an early age.

About the FOXG1 Research Foundation:
The FOXG1 Research Foundation has gained recognition as one of the fastest growing and innovative global rare disease organizations. Notably, it has been honored as a Chan Zuckerberg Initiative "Rare As One" partner, reflecting the foundation's commitment to making a significant impact in the lives of individuals affected by rare diseases. Through pioneering research, advocacy, and collaborative efforts, the foundation strives to advance treatments and therapies for FOXG1 syndrome and other childhood neurological diseases including Autism. By focusing on cutting-edge solutions and fostering partnerships, the FOXG1 Research Foundation is at the forefront of driving meaningful change within the rare disease community.

www.foxg1research.org | www.joyfullyjosie.love

Read More
News, Announcement Nicole Johnson News, Announcement Nicole Johnson

Dr. Soo-Kyung Lee, FOXG1 Research Foundation Scientist, Earns Grant from Simon Foundation Autism Research Initiative (SFARI) for Genomics of ASD: Pathways to Genetic Therapies

Dr. Soo-Kyung Lee, FOXG1 Research Foundation Chief Scientific Officer, named awardee of Simon Foundation Autism Research Initiative (SFARI) grant for Genomics of ASD: Pathways to Genetic Therapies

FOXG1 Research Foundation CSO Named The Simons Foundation Autism Research Initiative (SFARI) Grantee 2022 Genomics of ASD: Pathways to Genetic Therapies

2022 Genomics of ASD: Pathways to Genetic Therapies awardees announced

The Simons Foundation Autism Research Initiative (SFARI) is pleased to announce that it intends to fund 15 grants in response to the 2022 Genomics of ASD: Pathways to Genetic Therapies request for applications (RFA).

Grants funded through this RFA are intended to advance our understanding of the genetic basis of ASD and the molecular and cellular consequences of genetic risk, and to provide a foundation for the development of treatments for select genetically defined forms of the condition.

Applications in response to this RFA were sought in three broad areas: (1) integrative analyses of multi-omic ASD data, (2) functional analysis of variants associated with ASD risk genes and (3) gene-targeted therapies. Proposals that span the different focus areas were encouraged, as were collaborations between academic and industry partners. Furthermore, SFARI encouraged proposals that focused on a subset of 50 genes from the SPARK gene list; these genes were selected, for a variety of different reasons, as strong candidates for the development of translational programs.

“SFARI is honored to support this group of awardees, whose research promises to not only elucidate the neurobiological pathways that are regulated by autism genes, but to also identify new therapeutic targets and strategies,” says SFARI executive vice president Kelsey Martin.

SFARI intends to provide approximately $15.7 million in funding over the next three years to 27 investigators as part of this program.

“SFARI is pleased to fund these projects under the 2023 Genomics RFA,” says SFARI senior scientist Julia Sommer. “We hope that the combination of additional insights into the genetic basis of ASDs and a better understanding of the molecular and cellular changes brought about by genetic risk factors will create a fertile ground for the development of genetically informed therapies.”

The projects that were selected for funding focus on several different risk genes and conditions, including GRIN disorders, Rett syndrome and SLC6A1-related autism disorder. A variety of different approaches and methods will be used, including high-throughput screens to ascertain the functional effects of autism variants, and the development of antisense oligonucleotide and adenoviral vector-based gene therapies.

The projects that SFARI intends to fund are:

Marta Biagioli, Ph.D. (University of Trento)
SINEUP RNAs: a new platform for treating haploinsufficiency in autism spectrum disorders (ASD)

Fikri Birey, Ph.D. (Emory University)
Uncovering phenotypic convergence across high-risk autism genes using forebrain assembloids

Arjun Krishnan, Ph.D. (University of Colorado, Denver) and Julia Ganz, Ph.D.(Michigan State University)
An integrative framework to unravel the genes, gene networks, cell types, and developmental states underlying ASD-associated GI dysfunction

Soo-Kyung Lee, Ph.D. (University at Buffalo)
Development of therapeutics for FOXG1 syndrome using patient-specific human iPSC and mouse models

Jingjing Li, Ph.D. (University of California, Berkeley), Arnold Kriegstein, M.D., Ph.D. (University of California, San Francisco), Michael Snyder, Ph.D. (Stanford University) and Mohan Babu, Ph.D. (University of Regina)
High-resolution proteome mapping in the developing human cerebral cortex to uncover mutationally convergent pathways in autism spectrum disorders

Matthew MacDonald, Ph.D. (University of Pittsburgh) and Bernie Devlin, Ph.D.(University of Pittsburgh)
Putting genes associated with autism in their neurobiological context by transcriptomic and proteomic analyses

Randall Platt, Ph.D. (Swiss Federal Institute of Technology in Switzerland)
High-throughput precision gene editing and multi-omics profiling of patient-specific CHD8 variants in human-derived stem cells and induced neurons

Elise Robinson, Sc.D. (Massachusetts General Hospital), Luke O’Connor, Ph.D.(Broad Institute of MIT and Harvard), Michael Talkowski, Ph.D. (Massachusetts General Hospital) and Kaitlin Samocha, Ph.D. (Massachusetts General Hospital)
Identifying functionally convergent genetic factors associated with autism

Yufeng Shen, Ph.D. (Columbia University Medical Center), Brian O’Roak, Ph.D.(Oregon Health & Science University) and Jacob Michaelson, Ph.D. (University of Iowa)
Triangulation of missense variant impact through multimodal modeling and functional assays

Max Staller, Ph.D. (University of California, Berkeley)
Functionally characterizing genetic variants in the activation domains of ASD-associated transcription factors

Michael Wells, Ph.D. (University of California, Los Angeles)
Cell village-based detection of shared molecular and cellular defects across autism risk factors

Anne West, M.D., Ph.D. (Duke University School of Medicine)
Orchestration of synaptic gene regulation by H3K27me3-dependent modulation of chromatin architecture

Hyejung Won, Ph.D. (University of North Carolina at Chapel Hill), Kristen Brennand, Ph.D. (Yale University) and Nan Yang, Ph.D. (Icahn School of Medicine at Mount Sinai)
Reciprocal impacts of rare and common polygenic risk architecture for autism into biological measures

Timothy Yu, M.D., Ph.D. (Boston Children’s Hospital)
Piloting gene- and mutation- specific ASO therapies for ASD

Zhaolan (Joe) Zhou, Ph.D. (Perelman School of Medicine, University of Pennsylvania)
Understanding the epigenetic contribution to autism

Read More
News, News Interviews Nicole Johnson News, News Interviews Nicole Johnson

San Francisco Business Times: Unlikely Drug Hunters: How two mothers are finding hope in searching for their children’s cures

SF Business Times: Kimberly Nye and Nasha Fitter both founded organizations to seek cures for afflictions suffered by their children. Nasha Fitter didn’t have time. There had to be a better, faster way, she thought — not just for her daughter, but for other people with rare diseases. Fitter tapped her tech and entrepreneurial background to create a nonprofit, the FOXG1 Research Foundation.

Nasha Fitter didn’t have time. There had to be a better, faster way, she thought — not just for her daughter, who recently turned 7, but for other people with rare diseases.

Fitter tapped her tech and entrepreneurial background to create a nonprofit, the FOXG1 Research Foundation, to try to find a cure for the 100 or so patients known to have the condition at the time. The foundation worked on a natural history study, which in ultra-rare diseases can serve as a placebo arm in a clinical trial. The foundation also creates cell lines, conducts drug screens and oversees gene therapy pilots.

“It’s insane, as parents, that we’re building mouse models and cell lines,” Fitter said. “It’s insane to me that this is what we have to do.”

In a world of little hope — where parents of children with rare genetic diseases are told there currently is little or nothing that will make their kids well and often no existing effort to discover something that will — moms and dads become the most improbable of drug hunters. Within days of a diagnosis, often despite no background in the life sciences, parents latch on to experts and start reading scientific journal articles. They learn about genetics and drug development, and they explore wonky concepts like yeast and animal models and drug-testing assays.

With no guarantees of success, those parents embark on odysseys that have tripped up Ph.D.s and MDs and seasoned drug- development executives.

In essence, they make their own hope.

Chan Zuckerberg Initiative assistance

When added together, rare diseases are anything but rare. In all, 350 million of the 8 billion people globally — more than 4% of the population — have one of the 10,000 known diseases that fit the U.S. definition of “rare,” fewer than 200,000 patients.

Only 5% of those diseases have Food and Drug Administration- approved therapies.

“I always say, ‘Yes, SLC13A5 is rare, but it’s not rare in my house,’” said Kim Nye, whose oldest daughter Tessa and son Colton have mutated copies of the SLC13A5 gene that cause a type of epilepsy. “I hope we can figure out how to make all these things scalable.”

All but a handful of drug companies, such as San Rafael’s BioMarin Pharmaceutical Inc. and Ultragenyx Pharmaceutical Inc. of Novato, have shied away from rare disease drug development. For many companies, the risk, time and money it takes to develop a drug — $1 billion over 10-plus years of work, by industry estimates, to take a single drug from lab bench to patient bedside — is more efficiently spent on a treatment for hundreds of thousands or millions of patients than for a handful.

Parents and other loved ones of rare-disease patients often try to fill the void.

“When a disease is so rare, the chance that any given academic is going to come across enough patients to do a natural history study is virtually zero,” said Tania Simoncelli, the vice president of science in society at the Chan Zuckerberg Initiative. “The only way to study it is to build a patient community. Who’s going to do that? Not some investigator trying to get tenure.

“The patient community has to do that work. They shouldn’t have to, but they have to.”

The mission of the Chan Zuckerberg Initiative — a 7-year-old effort backed by pediatrician Priscilla Chan and her husband Mark Zuckerberg, the co-founder of Facebook and CEO of Meta Platforms Inc. — is to support science and technology to prevent or cure all diseases by the end of the 21st century.

Simoncelli joined CZI five years ago following time in the White House Office of Science and Technology in the Obama Administration, the Food and Drug Administration and the ACLU, where she was an adviser to the organization’s efforts to stop genes from being patented by companies. Her goal at CZI is no less ambitious: help patient organizations build networks that leverage knowledge to make rare-disease therapy development more efficient and effective.

CZI, based in Redwood City, created the “Rare As One” project initially to fund 10 pilot patient groups. Instead, the organization received more than 300 applications, and CZI in 2019 funded 30 three-year, $600,000 grants to help grassroots patient organizations build infrastructure, including paid staff, scientific advisory boards, websites and other community tools.

One of those groups was the Nye family’s TESS Research Foundation in Menlo Park.

The Rare as One network two years ago added a second cohort of 20 organizations.

“Patients have real expertise to bring to the table,” Simoncelli said. “They have the motivation and the insights to generate hypotheses. We see this over and over again, and yet it’s not really recognized.”

There are other, similarly audacious efforts to speed up the search for rare disease therapies.

Ultragenyx bootcamp

As vice president of business development at Ultragenyx in 2017, Dr. Yael Weiss organized a bootcamp at the company’s Novato campus for patients and parents looking to build new therapies. Those sessions, including an upcoming one in April, attract 20-25 participants.

In all, the bootcamp has had 110 attendees representing 85 advocacy groups.

The bootcamp aims to familiarize patients and parents with the drug-development pathway, jargon and options available to them. It also offers an opportunity to hear from experts in the rare- disease space and helps create a “mini peer group,” Weiss said.

“Times are changing and these amazing parents aren’t waiting for industry to pick up their programs,” Weiss said. “They are just doing it.”

Weiss also is founder and CEO of Mahzi Therapeutics Inc., launched two years ago with early funding from Ultragenyx and others, to mentor and support patient groups that fund early research, then in-license programs to continue drug development.

“There is so much activity in this space, and the Bay Area is a hub for some amazing parents and a great rare community, each with heartbreaking and heroic stories,” Weiss said.

Yet parents and patients continue to face sizable roadblocks, including money, time and know-how for navigating the complexities of early-stage drug research and development.

Natural history studies, for example, often rely on far-away academic centers that are challenging to reach when traveling with a young child with a rare disease. On her way to Amara’s third visit to a site three hours away, for example, Fitter’s daughter had a seizure and vomited in the car.

Fitter turned back for home.

“It’s just a ridiculous model. Health care is a very slow-moving industry,” said Fitter, who founded the tech startup Schoolie and was a director at Microsoft Corp. “There’s so much regulation. It’s always slow to change. There’s a lot of nervousness.”

Fitter landed a $482,000, four-year grant from CZI and worked with Ciitizen Corp., a Palo Alto digital health records startup that had focused on cancer. They created a natural history study that included Nye’s TESS Research Foundation and four other groups, using machine learning to scrape records and give uniformity for a picture of those neurological conditions.

“Gathering records is a big hurdle,” Nye said. “Not all hospitals were even using electronic medical records. I had a binder of printouts.”

Fitter joined Ciitizen in October 2018 as vice president or rare and neurological conditions. The company was bought last year by San Francisco-based genetic testing company Invitae Corp.

Patients, researchers and nonprofits can receive its data for free; drug companies pay for access.

“Using technology to gather information in homes, that is my passion. How can we eliminate these unnecessary complications that we are creating for these patients?” Fitter said. “Rare diseases are where we can experiment with new technology.”

‘This is what I am now’

Rare disease research and development is not a career Kim Nye saw herself in when she and her husband were in graduate school near London and Tessa was born with what would turn out to be SLC13A5 epilepsy. Nye, studying law, literature and history in Greek and Latin, was 23 years old.

Now she is a parent of two children with a rare disease — Tessa now is 19 and Colton is 9 — along with being a patient advocate and an expert in all things SLC13A5.The TESS Research Foundation, founded in 2015, supports research and helped take a potential gene replacement therapy to the cusp of a first-in-human clinical trial.

“This is what I am now,” Nye said. “I don’t have the degrees behind it and I don’t have the same type of education, but I have learned from mentors who I think are the best of the best. It’s really been a graduate-school education of sorts, just nontraditional.

“I know who I am, and it’s a role that’s needed. It’s just not a role that has a name.”

Ron Leuty

FOXG1 CEO and Mom, and Rare Disease Warrior, Nasha Fitter in the San Francisco Business Times

Nasha Fitter and Kim Nye started rare disease foundations to cure their children’s diseases: SF Business Times

 

Senior Reporter - San Francisco Business Times

https://www.bizjournals.com/sanfrancisco/news/2023/03/03/rare-disease-cures.html?s=print 4/7

3/3/23, 8:41 PM

FOXG1 Research Foundation, TESS Research Foundation seek rare disease cures - San Francisco Business Times

Read More
News Nicole Johnson News Nicole Johnson

The most personalized medicine: Studying your own child’s rare condition

Article from Spectrum News, the leading site for autism research news. Excerpt:Attracting parents who are also scientists to the cause only turbocharges those efforts. Nasha Fitter, a cofounder of the FOXG1 Research Foundation, a parent-led foundation for research on an autism-linked condition called FOXG1syndrome, could hardly believe it when she stumbled on a 2017 Facebook post by FOXG1 parent Soo-Kyung Lee about a grant she and her husband, Jae Lee, both respected neuroscientists, had secured. “Hold up, you guys are parents and you’re scientists?” she remembers thinking, even before she knew of their expertise and reputation for rigor. The Lees now lead the FOXG1 Center of Excellence at the University at Buffalo in New York State and receive considerable funding from the foundation. FOXG1 families are unfortunate in many ways, Fitter says, “but we’re very fortunate with Soo and Jae.”

The day Michael Boland’s son was born in July 2018 was blissfully normal. It had been a routine birth, and little Lukas aced the Apgar, a standard health test given to newborns. The next day, Boland made a quick trip home. As he walked back into the hospital room, he saw Lukas move in a sudden, odd way.

“What was that?” he said to his partner, Maja Horn.

“We saw him do that earlier,” Horn said.

A first-time mother, she wondered if the brief, jerky movements were typical of newborns. Or maybe it was hiccups?

Boland suspected otherwise. A cell biologist at the Institute for Genomic Medicine at Columbia University, he studies developmental and epileptic encephalopathies. He knew what seizures looked like in infants. When Lukas moved the same way again an hour later, Boland alerted the doctors. They whisked Lukas to the neonatal intensive care unit and put him on antiseizure medication. Two and a half weeks later, genetic testing revealed a mutation in a gene called STXBP1.

“Oh my God, I was devastated,” Boland says. “I had an idea what we were facing.”

Finding focus: Using stem-cell-derived models, Michael Boland’s team is testing two gene therapies for STXBP1 syndrome. Photograph by Akasha Rabut

He had not studied STXBP1, or syntaxin binding protein 1, but he knew that it plays a critical role in the transmission of electrical signals between neurons. Researchers had identified mutations in STXBP1 that reduce that signaling as a cause of infantile epileptic encephalopathy in 2008. Since then, increases in genetic testing have revealed STXBP1 encephalopathy in about one in 33,000 children. Clinical symptoms vary, but include epilepsy and, often, severe cognitive impairment; about 20 percent of children with the condition exhibit autism traits. Of the most affected children, Boland says, “they’re not going to be potty trained ever, they’re not going to learn to dress themselves.”

A couple of months after Lukas’s birth, Boland sat down with his colleagues at the Institute, David Goldstein and Wayne Frankel, and told them what was going on with Lukas.

“Wayne was like, ‘You’ve got to be kidding me!’” Boland remembers. “David’s jaw hit the table.”

“When do we start working on STXBP1?” Boland asked them.

“Immediately,” they responded.

With that, Boland became one of a handful of scientists in an unenviable but potentially important position: He would turn his heartbreak into hard data and study his own child’s condition. “I’m a scientist. . . This is my son. We have all of the tools here to do this,” he says. “It just feels like that’s what I was trained to do.”

In the world of rare autism-linked genetic syndromes, parents are already playing a central role, pushing to raise funds and advance investigations into their children’s conditions. “Parents are essentially kick-starting, and frankly, de-risking the research,” says Charlene Son Rigby, who in 2017 cofounded the STXBP1 Foundation, which has three parents on its science advisory board, including Boland.

Attracting parents who are also scientists to the cause only turbocharges those efforts. Nasha Fitter, a cofounder of the FOXG1 Research Foundation, a parent-led foundation for research on an autism-linked condition called FOXG1syndrome, could hardly believe it when she stumbled on a 2017 Facebook post by FOXG1 parent Soo-Kyung Lee about a grant she and her husband, Jae Lee, both respected neuroscientists, had secured. “Hold up, you guys are parents and you’re scientists?” she remembers thinking, even before she knew of their expertise and reputation for rigor. The Lees now lead the FOXG1 Center of Excellence at the University at Buffalo in New York State and receive considerable funding from the foundation. FOXG1 families are unfortunate in many ways, Fitter says, “but we’re very fortunate with Soo and Jae.”

Floor time: Cell biologist Boland plays on the floor with his son Lukas. Lukas, nearly 4 years old, doesn’t walk and only recently learned to crawl. Photograph by Akasha Rabut

Experts see little risk in the personalized research of people like Boland and the Lees, noting that ethical review boards and the peer review process help protect against conflicts of interest. Meanwhile, the upside of the urgency and commitment parent-scientists bring may be considerable. “Being extra super smart is great,” says William Dobyns, a pediatric neurologist and medical geneticist at the University of Minnesota in Minneapolis who has helped identify many single-gene brain disorders, “but focus and motivation, that’s one of the difference makers. That gets progress.”

STXBP1 and FOXG1 represent two of an ever-growing list of genes implicated in autism-related neurodevelopmental conditions over the past 15 years. Where once children might have been diagnosed with autism, severe intellectual disability, epilepsy or some combination of the three, genetic testing now pinpoints a causative mutation in about 40 percent of cases, according to Dobyns. (For autism without co-occurring conditions requiring high support, that number is far lower, in the low single digits, he says.) The more profound a person’s traits, the more likely it is that an explanation can be found in their DNA. Having a genetic diagnosis fine-tunes the prognosis for a child and reveals whether other family members are at risk. It also allows hope.

“Once we recognize a specific genetically defined disorder, then the possibility of developing targeted therapy is here,” Dobyns says.

Soo Lee understood that better than most. When her daughter Yuna was born in 2010, Lee was a rising star in the world of neurodevelopmental biology. Her research focused on the role of transcription factors, which regulate genes, during brain development. The demands of her career were intense — so much so that when her infant daughter showed signs of profound developmental delays, she worried it was somehow her fault for working too much. Yuna missed every milestone, had enormous trouble feeding and sleeping and had seizures beginning soon after birth. Magnetic resonance imaging (MRI) revealed microcephaly, a small brain, but genetic testing did not initially turn up any mutations. Yuna was diagnosed with congenital Rett syndrome, a catchall for children who have clinical similarities to the autism-linked condition.

The Lees pressed to keep searching for a genetic culprit. Soo Lee took to carrying Yuna’s MRI results wherever she went, including a multiday meeting for the National Institutes of Health held in San Francisco, California. There, she talked about her then 2-year-old daughter’s condition with a researcher who offered to consult a radiologist colleague who had deep experience reading pediatric neurological MRI results. A few days later, that radiologist reported that the abnormalities in Yuna’s brain structure might be tied to FOXG1, a gene so critical to brain development that mice lacking both copies do not develop a functional brain and die shortly after birth. (The same is true of STXBP1.)

The idea that her own daughter might have a condition related to a neurodevelopmental gene, encoding a transcription factor no less — the very thing Lee studied — seemed almost too coincidental to be believed. Although FOXG1 was well known, the syndrome related to FOXG1 mutations had only been named in 2011 and wasn’t yet widely recognized. When the Lees had Yuna tested for it specifically, the radiologist was proved right. Soo Lee reviewed the raw sequencing data herself to be sure. She estimates that Yuna was the 20th child in the world to be identified with FOXG1 syndrome. There are still fewer than 1,000 known cases, although there are likely to be many more who have not been identified.

The hallmarks of the syndrome include microcephaly, cortical atrophy and weak or missing connections between brain hemispheres, as well as seizures, cognitive disabilities, absence of language, movement disorders and, sometimes, autism. Children who have a completely inactivated copy of the gene, like Yuna, have more disabling traits than those with a more mildly affected version that produces faulty FOXG1 protein.

Yuna’s diagnosis prompted Soo Lee to make FOXG1 a centerpiece of her research. “I thought, this is what I have to do,” she says. Jae Lee, who had done important work on gene regulation of metabolism, joined her. “I was more than glad to drop everything else,” he says.


Expressing interest
: Biologist Soo-Kyung Lee with her daughter Yuna and her son Joon. Yuna cannot walk or speak, but she likes stuffed animals and toys that light up or play music. Photograph by Eric Tronolone

Much of the Lees’ home on a quiet cul-de-sac near the university is organized with Yuna in mind. The house features wide-open spaces and hardwood floors that can be readily navigated with a wheelchair. Construction on a small indoor swimming pool is underway, because Yuna enjoyed the hotel swimming pools they frequented when they drove across the country from Oregon to Buffalo to start their center in 2019.

Small and thin for a 12-year-old, Yuna usually wears soft clothing such as sweatpants and a fleece top, with her hair pulled into a ponytail atop her head with a fuzzy scrunchie. (Her dad has gotten very good at doing her hair in the morning.) She cannot walk or speak, but her family know what she likes — including stuffed animals and toys that light up or play music. After she gets home from her specialized school, she spends a lot of time in a play area they’ve created for her in an alcove off the kitchen. Her poor motor control means that she is constantly moving, but when her caregiver puts a sticker on the couch and encourages Yuna to go get it, the girl rocks and reaches her way to the couch. The Lees credit years of therapy and hard work. Her movement has become “more purposeful because she has better control,” Jae Lee says.

They take heart from other small, hard-won changes. Yuna never used to make eye contact with her parents. Recently she began glancing out the school bus window at them as they waved goodbye in the morning. One day when Jae did not join Soo in the driveway, Yuna looked far longer than normal. Soo says she believes Yuna was searching for her father. The next day Jae was back in position and Yuna, presumably satisfied, resumed her usual glance. “She’s doing much better than what I thought [was possible] 5 years ago,” Soo Lee says. “It’s a very subtle thing. Nowadays, I can tell what she likes, that she’s happy. It’s just so much easier to know who Yuna is.”

Play time: Lee helps Yuna peel stickers. Photograph by Eric Tronolone

The research that Boland and the Lees have conducted so far differs in the specifics but offers a basic science primer on how to tackle monogenetic conditions. First, establish viable models, beginning with mice, and use those models to investigate what exactly the genes of interest do in the brain. Because these conditions are developmental, address the pivotal question of whether the work of the gene is complete at birth or whether it continues and offers an opportunity to intervene. Finally, ask the ultimate question: Is it possible to reverse the damage and rescue what has been lost—in humans, not just in mice?

The Lees have focused their efforts on mouse models. The first one they analyzed lacked one copy of the FOXG1 gene and showed altered brain structure and behavior that mimicked the movement, learning and memory deficits seen in children with FOXG1 syndrome. The Lees have since made multiple mouse models that mimic various mutations found in people. And they have shown that FOXG1 helps establish the brain’s cortical layers and create the corpus callosum, which connects the left and right brain hemispheres.

Boland, too, is working with a mouse model of STXBP1, with help from Frankel, who has decades of experience in the field. But Boland also grows human pluripotent stem cells, which he coaxes into two different models: two-dimensional neuronal networks that look like lacy latticework, and three-dimensional brain organoids, which look like chickpeas yet faithfully recapitulate the early cell growth in developing brains. He has even created models using Lukas’s cells and his own. “[That’s] a 3D model of my son’s brain in a dish,” he says during a tour of the lab. The three models — neuronal networks, organoids and mice — trade biological complexity for granularity and together, Boland says, allow more nuanced comparisons of how typical and STXBP1 neurons communicate.

Personalized medicine: Boland grows 3D organoid models of his son’s brain in a culture dish. Photograph by Akasha Rabut

Fortunately, FOXG1’s work appears to be incomplete at birth, the Lees have found, and STXBP1 is critical to how neurons communicate throughout life. That leaves open the possibility of drug treatments or gene therapies. Boland and Frankel are focusing on testing two gene therapies for STXBP1: a traditional replacement therapy that adds back a functional copy of STXBP1 and an adaptation of CRISPR technology that upregulates the gene’s expression. (That work is supported by a grant from The Simons Foundation, Spectrum’s parent organization, and Boland is a part-time consultant for the Foundation.) Unpublished work in other labs has successfully stopped seizures and rescued learning and memory deficits in mice, Boland says.

The Lees are using their mice as platforms for drug screening. One therapy they tried in an unpublished experiment reversed some of the traits in FOXG1 model mice. “We wanted to confirm whether FOXG1 syndrome can be fixed,” Jae says. “The answer seems to be yes. We were just completely stunned.”

Despite the promise, treatment is not imminent for either of these conditions. At home, these scientists focus on being parents, not researchers. Half of Boland and Horn’s Manhattan living room is given over to a colorful rug with toys stacked around its edges. At first glance Lukas, at nearly 4 years old, looks like any child his age, with a cherubic round face. He sits tall on the rug (therapists compliment his posture) and gazes at his parents. But it’s soon evident that his behavior is more like that of a 1-year-old. His feeding issues mean everything he eats must be pureed. He doesn’t talk. He only recently learned to crawl. He might be able to walk by age 6 or so, though it won’t be coordinated walking, Boland says.

Each new skill — head control, sitting up, pulling up, crawling — was the work of many months or even years. Boland and Horn call them “inchstones” not milestones. Nonetheless, they say, Lukas is easygoing and engaged. He loves spinning tops, musical toys and board books. Lying on the floor with an Elmo book, he dips his head to the page and touches it with his lips, giving Elmo a kiss. Such social behavior feels like a gift, Boland says, while mashing up sweet potatoes, spinach and quinoa for Lukas’s dinner. “When he can give you those big beautiful brown eyes that stare into your soul, it makes it easier.”


Small steps
: Lukas doesn’t speak but is learning to express his needs through a communication device. Photograph by Akasha Rabut

During her pregnancy, Horn, who was over 40 and at increased risk for having a child with a disability, worried a little bit about that possibility. “Will you do everything you can?” she asked Boland. He said he would. But that was a hypothetical conversation, and the reality of Lukas’s condition was a shock. Over time, however, says Horn, a professor of Spanish literature at Barnard College in New York City, she has come to fully accept Lukas for who he is, and the experience of raising him has changed her “in every imaginable way.” She, too, has shifted her academic interests to think about perceptions of ability and disability. She is glad Boland is studying STXBP1 — that he is, in fact, doing everything he can. But she is not willing to try anything too risky on her child. Her focus is on cherishing Lukas as he is, “a child that’s so lovely and happy,” and facing the immediate future. “My hope is that he will be able to express his needs and wants on his [communication] device. . .to be able to say I’m hungry, I’m thirsty,” she says. “I think that’s totally within reach.”

Boland and the Lees have been changed as well, for better and for worse.

One Sunday afternoon, when Yuna was 5 years old, Soo Lee collapsed in the living room. She had developed vestibular neuritis, a destabilizing condition caused by inflammation, which Soo attributes to stress. Seven years later, she manages her condition with medication but must limit work hours, screen time and some daily activities like driving. When her 9-year-old son, Joon, “wants to show me a YouTube video, he says, ‘Wait, wait, let me lower the brightness,’” she says with a laugh.

Science is famously competitive and ego-driven; there is only so much money and recognition to go around. For Boland and the Lees, however, ego has less to do with it these days. Regardless of funding or support, Jae Lee says, “this is what we would be doing.” Interactions with other scientists are different, too. It used to be “like holding a poker hand,” Boland says. No more. “As a parent, I’m less of the poker player. I’m more like, these are my cards. If you can learn from me, then maybe that’ll help you develop a therapy faster than mine.”

BY LYDIA DENWORTH

Read More
News Interviews, News Nicole Johnson News Interviews, News Nicole Johnson

Global Genes Rare Leader: FOXG1 Research Foundation Co-Founder & Executive Director

Global Genes features FOXG1 Research Foundation Co-founder and Executive Director, Nicole Johnson as a rare Leader. Learn about the FOXG1 organization’s strategy, mission, guiding principles, Nicole’s management philosophy, and more.

The Basics
Name: Nicole Johnson

Title: Co-founder and Executive Director

Organization: FOXG1 Research Foundation

Social Media Links:

Disease focus: FOXG1 syndrome is a rare, pediatric, neurological disorder that greatly impacts brain development and causes severe physical and cognitive disabilities. FOXG1 syndrome is caused by a mutation to the FOXG1 gene, which is one of the first and most critical genes in brain development. There are currently about 900 known individuals with FOXG1 syndrome worldwide, with the diagnosis rate climbing steadily year-over-year. FOXG1 syndrome is typically a de novo (spontaneous, non-inherited) mutation, with multiple variants that affect individuals differently along the spectrum of severity. Most children born with FOXG1 syndrome are nonverbal, have severe cognitive and physical disabilities, experience intractable seizures, respiratory distress, cortical vision impairment, feeding difficulties, reflux, movement disorders, and more. Less-severely-affected FOXG1 patients present with autism spectrum disorder.

Headquarters: Sands Point, New York

How did you become involved in rare disease: Becoming involved in rare disease, science, and even medicine is the last thing in the world I would ever have expected or chosen as a career path. But, when my daughter Josie was diagnosed in 2014 at 2 years old with FOXG1 syndrome, it became the only area I was interested in dedicating my time to. There was just very little known about FOXG1 syndrome. At the time, there was not a concerted research effort underway for FOXG1 syndrome. It was lumped under Rett syndrome. On her genetics report it said congenital variant of Rett syndrome, but it’s not Rett syndrome. It’s a completely different gene with a variety of variants that all present somewhat differently. At that time, I knew that a real effort centered on FOXG1 syndrome had to begin and that I was at ground zero for what would grow into a much larger organization.

Previous career: Television producer for CNN, NBC, and worked in corporate communications. Founding partner for Qello Concerts streaming service, now called Qello Stingray.

Education: B.S. from Towson University in Maryland

The Organization
FOXG1 Organization’s mission: We are the parent-led, global, rare disease patient organization driving the research to find successful, precise therapeutics and ultimately a cure for every individual in the world with FOXG1 syndrome while deeply focusing on patient advocacy and support. It’s our mission to accelerate research to find successful therapeutics for FOXG1 syndrome and related neurological disorders.

Organization’s strategy: We’re centered in three main areas that are integral to driving drug development. We have a three-pronged approach. One is research. The second is data. Third is the patient community. We’re building a consortium of brilliant scientists to work together to deeply characterize the disease, answer the critical scientific unknowns, and test potential treatments ranging from cutting-edge gene therapy to nascent technologies. We have a ‘leave-no-stone unturned’ mentality. At the same time, our strategy is centered on covering all variants of the disease with a suite of assets that represent all the mutation categories, and then matching them to the coordinating patient data. That’s particular to how we go about things. Having mouse models, cell models for the missense mutation, the nonsense mutation, the deletion, and to be able to layer that over the data from the patients of those exact mutation types, is helping us to provide rich data on our patients and the disease.

Funding strategy: Since we launched in 2017, it’s been a grassroot roots effort with family and friends pulling everyone together. We do as much fundraising as we can, applying for grants, putting together our grants team, building strong teams within our organization. We have a fundraising committee now and we’re looking at all the different opportunities. Fundraising is one of the hardest things about this. We need millions of dollars, and we need people to care about a rare disease. Our fundraising strategy is to do everything we possibly can to raise money and we’re always trying to think outside the box for different ways to do it.

What’s changing at your organization in the next year: We’re just growing so fast. We’re building our team to meet our needs. I’m basically working 60 hours a week right now with a to-do list that would double those hours. We’re hosting the first-ever FOXG1 parents conference in November. We’ve had two science symposiums in the past, but this is the first time that we’re bringing FOXG1 parents from all over the world together. We’re hosting it on the beach in Florida so that we can provide parents and caregivers with a retreat-like experience and an opportunity to relax while we all connect and learn. Our worldwide foundation chapters are growing. We have a FOXG1 Research Foundation in Australia. We have an affiliate association in Spain and in France, and we have more in the works. We’re also about to announce the very first clinical trial for FOXG1 syndrome. This is for an epilepsy medication that is showing very good results for other epilepsy rare diseases.

Management Style
Management philosophy: I’m a producer at heart, coming from CNN, I can see everything that has to come together and all the elements to make it a success. I have somewhat of a positive, perhaps even spiritual, management philosophy. We don’t get the minutes of our lives back. And for our children, we don’t have time to waste. No matter what we’re doing, no matter who we’re working with, it’s imperative that we work smart, efficiently, innovatively, and carefully. But, most importantly, you need to feel good while you’re doing it. At the end of the day, for me, the most important thing for everyone is that the work we do feels good. Our lives are very hard as FOXG1 parents. Growing a global organization from the ground up, building it like a startup, working with industry, academia, parents, and more, with the goal to cure a rare disease in our children’s lifetime, is a stressful role to take on. Protecting our good energy is so important and you must identify what is draining that good energy and know when to call it. You must remove what’s draining you. And once you do, you open the door for much more productive and uplifting things. My management philosophy is not to be too rigid and allow for free-flowing communication because that is where the best ideas come. Stay organized and constantly maintain all the verticals but be nimble to change where change is needed.

Guiding principles for running an effective organization: We’re guided by these shared principles: Never feel locked into one way of doing things. Never think you know it all. Always challenge yourself/us to do better.

Our guiding principles are these questions: How can we do this better? What can we learn to improve ourselves? How is our current process working? What are the gaps that are slowing us down? How can we identify and solve them? What do we need to? What do we need to perform better?

Back to my spiritual style, I personally ask, are we leading with gratitude? I come back to this question often in my life and it always delivers. Breathe through the stress and come back to gratitude, and then and only then can you focus. And never lead with ego. I think this is common in our space, in business, and in life. I’ve seen how it’s the most counterproductive aspect in business. The goal is always, what can we do to help FOXG1 children live the healthy and able lives they deserve.

That means working as a team and seeing the big, holistic picture. And one more is just to value everyone and don’t forget your purpose. Every person, every touchpoint of this organization, is integral to our success. If you’re putting in one hour a month, or 60 hours a week, your time is valuable and appreciated. I want everyone to know this. I want everyone to smile knowing we’re here to change the landscape and to improve human life. We have a tremendous purpose, and it should always feel good.

Best way to keep your organization relevant: Be innovative. Be creative. Always reach out to people. Always make that connection. Always think, what can I be doing to keep my organization relevant. But you must be present. You must be out there. You found me to write this article. You found us. When you’re thinking innovation and you’re connecting with the greater rare disease space, and you’re seeing 10 steps ahead to reach your goal, you will be relevant.

Why people like working with you: I’m a good listener. I have a good way of hearing what people want to do and then turning it into action. I’m compassionate and most of all, it’s clear that I’m passionate about what we’re doing.  

Mentor: Orrin Devinsky, NYU Epilepsy. Bruce Leuchter, CEO of Neurvati, Daniel Fisher CEO of Tevard and Dravet father, John Crowley was an original mentor when Josie was first diagnosed. My cofounder Nasha Fitter is also a mentor, the Angelman FAST Foundation, Terry Jo Bichell from CombinedBrain. Mike Graglia from Syngap Research Fund. Those are just some of my mentors in this space. I’ve had mentors throughout my career in different areas. Myron Kandel from CNN financial news will always hold a special place. There is a new Netflix documentary out now about my writing mentor and friend, Ben Fong Torres.

On the Job
What inspires you: What inspires me most on the job is the FOXG1 children and their parents. Every single one of us is living an extremely difficult life. Every single parent that I come across just has this incredible, unique ability to advocate for their children. It’s the most inspiring love and passion that I get to see every day. The parents inspire me so much, but our FOXG1 children inspire me so much because they’re just amazing. I always say for the things that our children cannot do because of their disabilities, they make up for in this incredible, pure love and joy that comes out in every photo I see. I just want to give them the abilities and the healthy life that they deserve.

What makes you hopeful: The SMA story makes me very hopeful—that there is a gene therapy story out there for a rare disease that is working. While there are few actual approved cures out there right now, I believe we’re living in a time of scientific breakthroughs and that there will be a tipping point when we go from just a few successful gene therapies and just a small number of therapeutics approved for rare diseases to many. I’m keeping this mentality to prepare our organization for that many, for this tipping point, for precision medicine to treat the many symptoms our children experience, as well as to ultimately fix the gene.

Best organization decision: Starting the organization. We got together a team and we never looked back. I will also say having a strategy from the start to focus on every mutation category was one of our strongest decisions early on.

Hardest lesson learned: I went into it thinking that everyone would be very cooperative and learned that people think differently. Not everyone will understand the value of working as a team to help all FOXG1 children. It was hard for me to accept that there were people who have more need for control and they operate from a different place, a place of pride, rather than doing what is productive, helpful, and holistic. I’ve learned to remove any disappointing or counterproductive emotions about this and just put my head down and work as hard and smart as possible to always focus on the goal. I’ll always do what I can to find a cure for every child and adult in the world with FOXG1 syndrome. I know that I’m here for children that I won’t even meet one day, for children who aren’t even born yet. Keeping that in focus removes any disappointments we’ve encountered along the way.

Toughest organization decision: Choosing the research projects to fund is not always an easy decision. We receive proposals from many brilliant scientists at leading academic centers. Oftentimes parents on our team bring forward a scientist whose research proposal is meaningful to them. They’ve been talking for a while. Proposals can seem very promising to us and we get excited about them. But we know we cannot make decisions based on our parent-driven emotions. This is why we have a multi-disciplinary Scientific Advisory Board. They spend time vetting and evaluating research proposals. They find the holes, they ask the tough questions, they give great feedback. We value every single dollar that is donated to help us drive this science. It is our duty to be shrewd with the science we fund.

Biggest missed opportunity: I like to believe that anything that felt like a missed opportunity was just a redirection in the right direction. We recently spent so many hours trying to hire a director of development. We’re ready to bring someone with years of experience to help our non-for-profit development holistically. We must have gone through 60 applications and got down to two candidates. We underestimated the current competitive job market, and both candidates took other positions. Again, is this just a redirection to the right person to help us grow? I’m going to say yes. So, we are continuing to search for a great director of development to join our team.      

Like best about the job: The purpose. I never felt what it meant to have such a purpose in life before. I certainly loved being in the music industry and I loved working in television, but knowing that the work I’m doing here is going to impact human life is unlike anything I’ve ever imagined.

Like least about the job: The purpose. The fact that I’m here because Josie has FOXG1 syndrome is my least favorite thing about the job. I would love nothing more than to have a typical life for her and for my family. I would love for her to be running off the school bus right now, telling me about her day, grabbing food out of the pantry, and running off to her dance class and all these simple things that everyone around me experiences. She had a big seizure yesterday. She’s tube fed. She can’t talk to me. We’re having discussions wondering if she’s having migraines from her new seizure medicine. It’s a heavy life and I’m just so sorry for her that she suffers. And yet, I could start singing “The wheels on the bus” and she’ll smile. She’s so sweet and precious. It’s so hard for her. I would give anything to not be talking to you right now because the term rare disease doesn’t impact me in my life. That’s what I like least about my job.

Pet peeve: Hearing people chew. I was happy to hear this was a genetic condition called misophonia. That makes sense because my sister suffers from it much more than I do. Something happens to us when we hear people chewing. Chewing gum is the worst offender.

First choice for a new career: I’d be a singer in a band, I just have to learn how to sing first. I’d play the guitar too. It may or may not be true that my Josie’s name is inspired from Josie and the Pussycats from Archie comics.

Personal Taste
Most influential book: The Universe Has Your Back by Gabrielle Bernstein. I must have gifted this book to at least 20 people and also Deepak Chopra‘s Seven Spiritual Laws of Success is a guide for me.

Favorite movie: My son will tell you that every movie is my favorite movie. We just watched CODA, and that’s my favorite movie of the week. I have a 15-year-old son, Tanner, and we’re going through the list of all-time best movies, which is fun to do with your kid. Some of my favorites include Forrest Gump, Almost Famous, True Romance, and Dead Poets Society.

Favorite music
: My favorite band of all time is Phish, but I love everything from Motown to the Beatles. Bill Withers is a favorite, jazz, Bowie, classic rock, reggae, indie music, old school rap, A Tribe Called Quest—there’s nothing I don’t love.

Favorite food: New York pizza

Guilty pleasure: New York pizza and DIY Instagram videos. When you watch someone just do things themselves, like home renovation, they’re mesmerizing to me.

Favorite way to spend free time: First is just being with my family. I didn’t mind being stuck at home for two years with my people. Second is seeing live music, especially with the friends I love. Third is walking in nature.

 

Read More
News Interviews, News Nicole Johnson News Interviews, News Nicole Johnson

The Johnson Family - Changing the World Right Here in Port Washington

FOXG1 Research Foundation co-founder and Executive Director shared her story with her hometown local magazine called Port Washington Living. This feature article celebrates the Johnson family and Nicole’s work to find a cure for FOXG1 syndrome, while helping FOXG1 families around the world, including helping the FOXG1 family in the Ukraine to safety.

FOXG1 cofounder Nicole Johnson and her family - working to cure FOXG1 syndrome for every family in the world. Port Washington Living Magazine
Read More