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

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.

University at Buffalo launches center to find treatments for FOXG1 syndrome

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

2023 Impact Report

2023 marked six years of the FOXG1 Research Foundation. We are a parent-driven, global foundation with the mission to help improve the lives of every person affected by FOXG1 syndrome worldwide. We are immensely proud of the organization we have built and the resources we have made available to our community since 2017.

We are known in the industry as innovators focused on three equally critical areas: FOXG1 science, FOXG1 patient data, and FOXG1 patients and community. From advancing our gene therapy program, to building our own bioinformatics platform, to helping guide parents through the rare disease medical caregiver journey, this year has been a year of upward progress in all three areas.

Our community is mourning the loss of 8 children in 2023 alone. We must stop this from happening. We are grateful for this incredible team working collectively to advance this goal, and most importantly, to our donors who enable this work.

Here are some of the FOXG1 Research Foundation highlights from 2023:

• Raised >$1.5M ($7.5M to date)

• Concluded our gene therapy preclinical work to upregulate the FOXG1 gene, rescue symptoms, and pass preliminary safety measures 

• Finalized characterization of key FOXG1 animal models, which are critical for drug screening

• Hired Chief Drug Development Officer, Dr. Gai Ayalon from Neumora Therapeutics to lead us successfully to a gene therapy clinical trial with the FDA and other international regulatory agencies

• Named Dr. Soo-Kyung Lee our Chief Scientific Officer, a FOXG1 mother and esteemed neuroscientist  who leads the FOXG1 Research Center of Excellence at the University at Buffalo with a team of >20 members focused solely on FOXG1 syndrome

• Built FOXG1 bioinformatics platform where all raw scientific, genetic and clinical data is normalized and cleansed enabling drug discovery and data for accelerated drug development from novel AI tools 

• Published paper on FOXG1 syndrome from our FOXG1 patient registry; 3 more publications underway

• Submitted paper to Journal of Neurology on epidemiology of FOXG1 syndrome meta-analysis results 

• Joined pharmaceutical-funded Biomarker studies with CombinedBrain

• Implemented FOXG1 Parent Support Team with monthly support zooms and resourceful webinars

• Connect newly diagnosed families to resources, medical professionals, and other families

• Announced the first FOXG1 patient to our advisory board, bringing a FOXG1 patient’s voice to our community

• Remain sought-after thought leaders/ speaker on podcasts and conferences

Here are some of the things the FOXG1 Research Foundation is working on in 2024:

• Moving our gene therapy program from preclinical to clinical stages with a focus on GMP manufacturing of product and toxicology studies 

• The 2024 FOXG1 Science Symposium and Parents Conference in November in Florida, USA

• Continue preclinical projects around small molecule, RNA and antisense oligonucleotide (ASO) drug screenings while continue studying the FOXG1 gene’s impact on the brain 

• Undertaking a large body of pre-work for clinical trials: deciding clinical trial endpoints, publishing a Disease Concept Model, meetings with clinical trial sites, meetings with the FDA and international agencies 

• Collaborations with biopharma companies as potential partners for our drug development programs 

• Exciting new resources for families to help assist managing their medical journeys, which includes new parent support webinars, virtual support meetings, and more

• Publication on FOXG1 Natural History Study data and FOXG1 Epidemiology papers in peer-reviewed medical journals  

• FOXG1 Research Center of Excellence at the University at Buffalo official ribbon cutting

• Growing FOXG1 clinicians network towards Standard of Care Guide for FOXG1 syndrome

• Establishment of expanded biobank with Coriell

• Continuing to expand our toolkit of assets to evaluate current and future therapeutic approaches
  

2023 FOXG1 Research Foundation Media 

*CARETALK Podcast: Why Rare Disease Research is SO Important with FOXG1 Research Foundation CEO, Nasha Fitter: Rare Disease Research and Its Potential To Unlock Medical Mysteries

*Ranked #9 Top Podcast Episode on Apple Health!

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

Video Recap: The 2022 FOXG1 Science Symposium and Parents Conference

SFARI News: 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 

Cafe Mom: 'Power of Moms': This Mom Quit Her Job To Find a Cure for Her Daughter’s Rare Disease

Press Release: New Children's Book "Joyfully Josie" Aims to Spark Conversations Around Disabilities, Rare Diseases, and Inclusion

Enable Magazine: Disability Pride Month: Educating the next generation to create an inclusive future

CareTalk Podcast: Why Rare Disease Research is SO Important

Rare Disease Research and Its Potential To Unlock Medical Mysteries

We now live in an age where we are closer to being able to decipher the greatest medical mysteries than ever before. Rare diseases, which were once thought of as untreatable cases, could be at the forefront of unlocking some remarkable discoveries with their unique characteristics and symptoms.

With so many possibilities available for medical professionals looking into rare disease research and treatments, it is becoming increasingly important for healthcare workers and business alike to understand just how powerful this form of research can be. Not only will exploring this topic enables us to further dedicate resources towards pioneering treatments that may have previously been overlooked—but also provide a brighter outlook on potential cures for those affected by these and other conditions.

In an episode of the healthcare podcast, CareTalk: Healthcare. Unfiltered., titled “Why Rare Disease Research is So Important” co-host, David Williams is joined by Nasha Fitter, CEO of FOXG1 Research Foundation, which is dedicated to finding a cure for FoxG1 Syndrome and Vice President of RWE and Ciitizen Platform at Invitae, to shed light on the importance of rare disease research, the challenges it faces, and the promising developments in this field.

Understanding Rare Diseases: What They Are and Why They Matter

A rare disease is a medical condition that affects only a small number of people compared to the general population. The exact definition of a rare disease varies depending on the country and the organization providing the classification. In the United States, a rare disease is defined as one that affects fewer than 200,000 people, while in Europe, a disease is considered rare if it affects fewer than 1 in 2,000 people. Although each rare disease affects a small number of people, there are thousands of different rare diseases, and as many as 300 million people worldwide are living with a rare disease.

Genetic mutations or environmental factors can give rise to these conditions, with many having no cure or treatment. Despite their significance, rare diseases are often overlooked and lack funding, leaving those affected and their families to grapple with the consequences. Those living with rare diseases frequently face challenges in obtaining an accurate and timely diagnosis, and their families may have limited resources for treatment and support. Progress in research and treatment is essential to enhance quality healthcare for patients with rare diseases and their loved ones.

“Rare diseases are not that rare. When you add up all the, all the conditions and you know, now we're actually up closer to 10,000. But the truth is, the majority of rare diseases are actually defined as ultra-rare, where you have less than 2000 patients in the United States, and that is the big chunk of the problem”. – Nasha (CareTalk)

Rare Disease Research: The Path to Discovering Treatments and Cures

Rare disease research is a complex and intricate field that requires substantial expertise and resources. Scientists, physicians, and patient advocates pool their knowledge and expertise to identify and study rare diseases. Through a combination of laboratory experiments, clinical studies, and patient surveys, these experts aim to shed light on the underlying causes of rare diseases, as well as potential treatments.

“Only about 5% of the 7,000 or so known rare diseases have treatments, so that makes it a real challenge for families, foundations, pharma companies, anybody trying to do something about it. But there is hope, including the Orphan Drug Act, FDA, programs to speed development, advances in genomics, and the digitization and interconnectivity of patient data”. – David (CareTalk)

Struggles and Limitations of Rare Disease Research

Rare disease research faces a myriad of challenges that hinder progress towards finding effective treatments for those affected. One of the primary issues is the lack of funding available for research, as these diseases do not affect a large population. This leads to a lack of resources, expertise, and technology needed to conduct thorough research. The vast diversity in rare diseases makes it challenging to conduct clinical trials with large enough sample sizes to provide reliable data.

Further complicating matters, diagnostic tools may not exist, making it difficult to properly identify the disease in question. Additionally, there is a lack of interest amongst pharmaceutical companies, as marketing drugs for rare or orphan diseases may not be as profitable. These limitations necessitate a collective effort to raise awareness and shift priorities, as finding cures for rare diseases is crucial for both the affected individuals and the advancement of medicine as a whole.

“I think there's a lot more we can do to innovate and make this experience better and mainly just have clinical trials that are more effective. Even with everything we're doing, the majority of clinical trials fail. So we need better ways to track endpoints to make sure that, you know, these drugs actually have a therapeutic effect on patients track that effect”. - Nasha (CareTalk)

Promising Benefits and Advancements in Rare Disease Research

Advancements in rare disease research hold great promise for patients and families affected by these conditions. With the development of technologies like genome editing and CRISPR-Cas9, scientists now have unprecedented insights into the underlying genetic causes of rare diseases. This knowledge is driving the development of targeted therapies that can address these causes at their source, offering hope for improved outcomes and quality of life.

Additionally, advances in diagnostics and data sharing are enabling more accurate and rapid identification of rare diseases, reducing the time to diagnosis and improving access to appropriate care. Despite its many challenges, the benefits of this research are immeasurable. By understanding the underlying biological mechanisms of rare diseases, researchers can shed light on basic biological processes, leading to the development of new diagnostic tools and therapeutic options for patients with rare and common diseases alike.

Furthermore, rare disease research has the potential to uncover novel drug targets and biological pathways, ultimately contributing to a deeper understanding of human health and disease. As the field of rare disease research continues to grow and evolve, we can expect to see even more promising developments on the horizon.

“There’re ways that we need to think about innovative trial design. The good news is that there are a lot of companies innovating in the space. A lot of organizations looking for better endpoints, better biomarkers and the FDA is open to listen and so, and I think the F D A basically needs to be convinced”. - Nasha (CareTalk)

How Can Improvements in Rare Disease Research Help Unlock Cures and Treatments for Other Diseases?

Looking ahead, proactive research into rare diseases holds great potential for medical advancement. While it is impossible to predict the exact outcome of such work, the promising results call for greater investment and collaboration across institutions. As breakthroughs in rare disease treatment hold potential implications far beyond their specific clinical application, there is tremendous potential to unlock cures that may be applicable to a broad range of unexplainable illnesses.

By taking the time to further invest in research on these rare diseases and collaborating with multiple resources and experts, we can help find ways to ease suffering for many and better understand why certain treatments work or don’t work. It is our hope that increased access to research opportunities will bring about great advances in medicine that make these mysteries a thing of the past.

FOXG1 Research Foundation Co-Founder, CEO Nasha Fitter joins CareTalk Podcast to shed light on the importance of rare disease research, the challenges it faces, and the promising developments in this field.

Listen to this episode on Spotify Here

ABOUT CARETALK

CareTalk is the only healthcare podcast that tells it like it is. Join hosts John Driscoll (President U.S. Healthcare and EVP, Walgreens Boots Alliance) and David Williams (President, Health Business Group) as they provide an incisive, no B.S. view of the US healthcare industry.

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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

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

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

Help FOXG1 Ukrainian Family Rebuild!

UKRAINIAN FOXG1 FAMILY

THE FOXG1 Research Community successfully helped get a FOXG1 family of five safely out of the war-torn Ukraine.

Elena and her husband have been living a complete nightmare with 3-year-old FOXG1 daughter Eva, a 6-month-old baby, and Elena's mother. They have lost everything. Eva needs seizure medication, Sabril and Prisim. They need a home. They have to completely rebuild their lives in Poland.

PLEASE DONATE HERE

Thank you for any help. Every dollar will help them rebuild their lives.

This was only made possible due to the incredible humanitarian operation - Project Dynamo! They do the impossible to save lives!

To Support Project Dynamo please DONATE HERE

For more information about FOXG1 syndrome and The FOXG1 Research Foundation please visit www.FOXG1research.org

The FOXG1 Research Foundation is the global organization driving the science to find precision treatments and ultimately a cure for every child in the world with FOXG1 syndrome. At the same time we are dedicated to advocating for and supporting FOXG1 families through this difficult journey.

To additionally help donate to the science to change the face of this heartbreaking disorder, please go to www.foxg1research.org/donate

We can not do what we do without donations. We are so grateful for you help.

Please follow us on social media: @FOXG1Research #FOXG1Research

and reach out any time [email protected]

From the bottom of our hearts, thank you for helping Elena, Eva and their family!

*Donations are US currency.

COMBINED Brain Interviews FOXG1 Research Foundation Co-Founder, Nicole Johnson

For FOXG1 Awareness Month, Terry Jo Bichell, the Director of COMBINED Brain spoke to Nicole Johnson about her FOXG1 journey. Nicole discusses her daughter Josie, her family, and how the FOXG1 Research Foundation was created. Learn the FRF's research strategy and more.

One Rare Disease Mom and Patient Organization Leader to Another…

Terry Jo Bichelle is the founder of COMBINED Brain, The Consortium for Outcome Measures and Biomarkers for Neurodevelopmental Disorders that is devoted to speeding the path to clinical treatments for people with severe rare genetic non-verbal neurodevelopmental disorders by pooling efforts, studies and data. Nicole Johnson is on the board of COMBINED Brian and is the co-founder and Executive Director of the FOXG1 Research Foundation.

Terry Jo speaks to Nicole about her journey as a FOXG1 mom, from the early days of searching for her daughter Josie’s diagnosis to starting the FOXG1 Research Foundation. As Terry Jo says the FOXG1 Research Foundation has “really power packed” the work in four years to drive the science towards therapeutics for all individuals with FOXG1 syndrome.

Dallas Morning News: Where is Former American Airline CEO Tom Horton? Raising Awareness for a Rare Genetic Condition.

Horton jumped into the campaign to raise awareness for the rare FOXG1 syndrome after his infant granddaughter was diagnosed in 2020.

By Kyle Arnold – The Dallas Morning News

Former American Airlines chief Tom Horton watched from his second home in New York in March 2020 as the aviation world ground to a near-halt when the emerging coronavirus spread from Asia to the United States and across the globe.

Among Horton’s guests were his son Zach, Zach’s wife Courtney and their newborn daughter, Gianna. But as the pandemic wore on and the aviation industry struggled to find its footing, the Hortons were distracted by Gianna’s early-life progress.

“It was evident to all of us that she was just sort of missing critical milestones,” said Horton, whose primary residence is in North Texas. “She doesn’t scoot around and crawl, and she’s nonverbal but very happy and engaged with everyone that she’s around.” 

It was those early pandemic months, isolated from much of the world, that would eventually put Horton and his tiny granddaughter front and center in an emerging mysterious genetic condition known as FOXG1 syndrome that may have key links to other issues such as autism, schizophrenia and Alzheimer’s.

At the time of her diagnosis, Horton’s granddaughter was only the 800th person in the world verified to have the disorder, and only about 50 more have been added to that list since. FOXG1 is actually a gene present in all humans that helps direct early development brain function and motor skills. Children with FOXG1 syndrome display some common complications, such as developmental delays, along with difficulties eating, speaking and walking. Only now, after 19 months, can Gianna sit up without assistance, a milestone most children hit around 6 or 7 months of age.

In fact, the disorder is so new and so rare that there is little research into FOXG1 syndrome or the potential drugs that could be used to treat people with the disorder.

Tom Horton, now 60, is familiar with tough battles. In 2011, after a 25-year career at American Airlines in finance, he was named CEO and then the next morning had to place the historic Fort Worth-based air carrier with 100,000 employees into bankruptcy. It was a situation that ultimately ended in Horton’s departure as CEO two years later when the airline merged with US Airways.

In the seven years after stepping back from American Airlines, Tom Horton has kept a mostly low profile, working in consulting and sitting on three corporate boards, including Qualcomm, General Electric and Walmart. Most recently, he has taken a position with a private equity firm in New York called Global Infrastructure Partners that has ownership in airports and other aviation-related businesses.

 Then, in May 2021, Horton and his bubbly redheaded granddaughter appeared in a YouTube video for the FOXG1 Research Foundation, trying to raise money to get existing pharmaceuticals into testing for treatment of people with the genetic disorder. Horton put up $1 million of his own money and started reaching out to his contacts in the business world to do more.

“The last three years have really been focused on the basic science to understand from a biological level how this syndrome presents in children,” said Nicole Johnson, executive director of the FOXG1 Research Foundation, whose daughter was one of the earliest diagnosed cases of FOXG1 syndrome. “And now we’re moving into translational science where we can actually start testing potential therapies in models and see if we have any potential treatments.”

Johnson said it’s an exciting time for research into genetic diseases. A team of scientists won the 2020 Nobel Prize in Chemistry for research into CRISPR gene-editing technology. Global teams of scientists were able to develop a handful of COVID-19 vaccines in less than a year in response to the global coronavirus pandemic.

Those kinds of technologies could help develop treatments for FOXG1 syndrome, but only if there is money and attention to do so, Johnson said.

“I think we’re at an amazing moment in history, and I really think there’s an opportunity for meaningful change,” Horton said.

As for the airline industry and his former employer, Horton said he keeps close tabs, especially during the turmoil of the last year.

“It’s extraordinary what they’ve been through,” he said. “I think it really speaks to the resilience of the people that work at these companies and lead them that they’re recovering the way they are.”

How the Ciitizen FOXG1 Platform Drives Research and Helps Parents Manage Medical Care

Being a FOXG1 parent can be extremely overwhelming, especially when it comes to managing medical care.

In the rare disease world, it seems like many families have to become experts on their child’s diagnosis, so that they can teach their doctors and professionals about their children. If you’re lucky, you end up at a healthcare institution that has maybe a handful of kids with the same diagnosis, and you may have to go through several medical institutions before you get there.  With advancing technology, wouldn’t it be great if that clinical data could be compiled for you, stored for review at any time, and shared easily with your physicians?  

Ciitizen has a free service to help patients do exactly that!

What is Ciitizen?

Ciitizen is a free service that helps patients get more out of their healthcare records, by giving you access to all of your child’s medical records in one easy place. The best part, they do all the work for you.

For the FOXG1 platform, it only takes 10 minutes to sign up and then the team at Ciitizen takes it from there. Once everything is compiled, you just log in and see your child’s medical records at any time and you can share them with whomever you choose.

However, they don’t stop there--while parents benefit immediately from this service--Ciitizen has created an efficient process to extract information from the medical records they’ve already collected and continue to collect in order to produce a regulatory-grade natural history study for our community.

A New Kind of Natural History Study

Ciitizen’s machine learning and expert team analyze the digitized, de-identified patient data collected for all the FOXG1 patients within the Ciitizen platform. Ciitizen employs a team of experts in HIPPA law and medical coding, genetic counselors, software developers, and scientists to apply world-standard terminologies (like SNOMED codes, RXNORM codes, etc) to FOXG1 compiled data.

Traditional Natural Histories are essential tools for clinical trials, but they are prohibitively expensive, very time consuming, and they often require patients to resubmit to testing they have already undergone.

Ciitizen makes it possible to quickly and inexpensively utilize existing medical information to create a retrospective natural history to help better understand our children. These findings are available to families and shared with academic researchers and consented non-profits at no cost. And patients do not need to travel to academic sites.

The FOXG1 Ciitizen platform can save us years in getting treatments for FOXG1!

How This Supports Clinical Trials

To test a treatment, we need actual physical measures that show progress over a range of patients with different ages, genetic backgrounds, severities, and medications. Often companies developing treatments in rare diseases like FOXG1 need to establish and fund lengthy natural history studies in order to prove efficacy. This is costly, and it is not easy on patients.

In order to keep Ciitizen free for patients, Ciitizen charges commercial entities a license fee. This fee is lower than if these commercial entities established their own Natural History Study. It's also faster since the Ciitizen data is ready to go but traditional studies will take at least a year. Even better, Ciitizen shares a percentage of any licensing fee back to the foundations working on the FOXG1 community, so we can continue investing in our community!

Who can join?

The goal is to include at least 400 FOXG1 patients over three years. We are adding patients in cohorts. We launched the first cohort of 50 US patients in January.  The second cohort will open to 50 more patients and this time it is open to other countries as long as the patient’s medical records are in english. As part of our grant, we are adding validated medical translators to include  more languages later this year. 

How do I sign up?

Right now there is a Waitlist. We recommend you join this ASAP! We will be emailing everyone on the waitlist to make sure you join before it’s full. 

The Ciitizen portal for FOXG1 patients will open on May 12th, 2021.

There will only be 50 spots open. Get ready to grab one of those 50 spots by making sure you have the following read to roll:

We will walk you through the process!

We will host webinars for different regions: The US, UK & Canada, Austrailia and NZ, and Taiwan

Please join the webinar for your region so that we can walk you through the process and help guide you on important details about accessing your medical records.

The webinar links will be the FOXG1 Research Parents Connect group and will be emailed to everyone on the waitlist..

JOIN THE REGISTRY FIRST!

If you have not done so already, it’s imperative that patients have a registry profile before being added to the Ciitizen natural History Study.

Please go to the Patient Data Center and make sure your child’s dashboard is set up with his/her genetics report uploaded.

“Measurable improvements for our Kids”

A final note: when a pharmaceutical or biotech company wants to develop a treatment for a rare disease and they are choosing which rare disease group to invest in, they will want to know that the community is easy to work with. They will need to know that if they ask anything of our FOXG1 parents that can measurably improve our children’s lives, that we will be engaged, and actively involved.

This is why singing up for the NHS is the first step to show that we are the rare disorder they should choose!

We’re truly in this together!

Reach out to [email protected] with any questions.

A Daughter's Rare Disease Brings Mother-Father Researchers to Buffalo for Answers

Soo-Kyung Lee, Empire Innovation Professor of Biology at the University at Buffalo, has been driven to focus greater attention on FOXG1 syndrome since her daughter, Yuna, was diagnosed with the neurological condition almost nine years ago.

Douglas Levere/University at Buffalo

Maybe Yuna Lee was built to be in Buffalo.

The 11-year-old – whose name means “snow girl” in a Korean dialect – was born during a rare January snowstorm in Houston, where her parents worked as medical researchers at Baylor College of Medicine.

Yuna seemed a typical newborn, but things changed in months that followed. Her head didn’t grow quickly enough. Seizures became common. She missed developmental milestones.

It took two years for doctors and top U.S. neurologists to tease out a diagnosis, which at first seemed unfathomable to her mother, Soo-Kyung Lee, a leading researcher in genetic brain disorders.

Yuna had FOXG1 syndrome, a rare condition caused by a random mutation in a key gene needed during fetal development to set the stage for speech, mobility and thought.

“Yuna was born in the right place, to the right mom. She kind of came to the right family,” said Jae Lee, her father, who for most of his career focused on diabetes and metabolic research.

The Lee parents, both biology professors, spent the bulk of the last decade at Oregon Health and Science University, on the West Coast in Portland, slowly taking more professional time on their daughter’s condition – until they were drawn in summer 2019 to the University at Buffalo by the prospect of creating a center of excellence in FOXG1 research.

Jae Lee, above, and his wife, Soo-Kyung Lee, natives of South Korea, came to Buffalo from Portland, Oregon two years ago with aims to create a center of excellence in FOXG1 research.

Douglas Levere/University at Buffalo

Their lab on the UB North Campus already has yielded greater understanding about how the related syndrome develops, raising hopes that their work could one day help with breakthrough research and treatment, including for related conditions such as autism, Alzheimer’s disease, epilepsy and schizophrenia.

Much work remains, Soo-Kyung Lee said.

The FOXG1 gene, once called “Brain Factor 1,” is a master regulator that is key to establishing cells that build the central nervous system, particularly the forebrain.

Yuna lacked a nucleotide, Number 256 in the 86th amino acid of one of two copies of FOXG1, which has 489 amino acids. Those born with such mutations on both copies cannot survive.

This and similar mutations almost always happen randomly, as was the case with Yuna.

Her mother has long used genes in the FOX family, including FOXG1, in her research.

Roughly 400,000 babies born worldwide have neurological disorders caused by random mutations.

Dr. Joseph Gleeson, a neurogeneticist at University of California San Diego, told the New York Times for a 2018 story on the Lees that doctors used to lump all those conditions together under autism or other categories before genetic sequencing became more common and provided more clarity.

“It’s really changing the way doctors are thinking about disease,” Gleeson told the Times.

Only about 650 people in the world are known to have FOXG1 syndrome, although FOXG1 genes also play a role in several other neurological conditions.

An estimated one in 68 children is diagnosed on the autism spectrum. More than 44 million people have Alzheimer’s or other forms of dementia worldwide. More than 2 million Americans have epilepsy. Roughly the same number have schizophrenia.

Yuna cannot talk, walk or eat on her own. She lacks control of her bowels. For years, she found it hard to sleep. She has learned to sit up and is making other slow, steady progress with help from physical, occupational and speech therapy. She communicates basic needs with her eyes and other facial expressions. She and her family live in Amherst.

She and her brother, Joon, 8, attended Maple East Elementary School before the pandemic, but have been learning at home because of coronavirus risks for Yuna. An experienced caregiver looks after the children while the Lees work mostly from home.

“It's not ideal,” Jae Lee said. “We look forward to the day that we can send Yuna back to school and back to the clinics, but we've been coping as well as we could have under the circumstances.”

Meanwhile, related research progresses. Those financially supporting the work of the Lees include New York State, the National Institute of Neurological Disorders and Stroke and the FOXG1 Research Foundation.

FOXG1 research could have implications for several neurological diseases, said Soo-Kyung Lee, including autism, Alzheimer’s, epilepsy, and schizophrenia.

Douglas Levere/University at Buffalo

November 2020 Research Update : Creyon Bio Takes on FOXG1 for ASOs!

We are so excited to deliver this Research Update during FOXG1 Awareness Month! 

1. Two Biotechs are investing in FOXG1 syndrome!  

2. We’re moving into Phase Two and Phase Three of our Path to a Cure!

1. We have Multiple Biotech Investments in FOXG1!

When we launched The FOXG1 Research Foundation in 2017, our goal was to develop the science needed for biotech companies to take us on. As a result of our investments made in developing patient-derived stem cell models, animal models, developing rich patient data, and having amazing community support, we were able to attract the world class talents of Taysha Gene Therapies and Creyon Bio to work on FOXG1 syndrome!

Taysha Gene Therapies: We’re thrilled to announce that Taysha Gene Therapies is developing TSHA-117 for FOXG1 Syndrome. Because the condition requires replacement of dose-sensitive genes, one investigational approach the company plans to explore is using its novel miRNA target panel, which is designed to enable the product candidate to maintain safe transgene expression levels in the brain.

Taysha is focused on developing AAV-based gene therapies specifically for monogenic CNS diseases. Dr. Sarah Sinnett at UT Southwestern leads the FOXG1 syndrome pre-clinical program. In addition, Dr. Sinnett and Dr. Steven Gray, also at UT Southwestern, are working on developing novel approaches for Rett syndrome. Read the announcement here.

Creyon Bio for ASO therapy: ASOs or “antisense oligonucleotides” are an exciting disease-modifying therapeutic approach showing real results in the Angelman and Batten Disease communities.
We are honored and excited to announce a partnership with Creyon Bio to explore and hopefully advance new oligonucleotide based therapeutics for the treatment of FOXG1 syndrome. Creyon Bio is focused on making new gene-centric medicines affordable and rapidly available to patients globally.  Creyon Bio is adopting advances in computational chemistry, biophysics and ML/AI to build a scalable platform that will transform the way oligonucleotide-based medicines (OBMs) are created. The Creyon team brings decades of experience in quantitative biology, genomics and OBM development and is excited to forge a strong collaboration with the FRF Science Team, including Dr. Alysson Muotri, Dr. Soo-Kyung Lee and others. 

NOTE: The collaboration described herein is subject to the negotiation and execution of definitive legal documentation by FOXG1 Research and Creyon.

2. We’re right on trajectory along the Path to a Cure!

Thanks to all of your help, we were able to create the necessary models to understand FOXG1 syndrome as planned. We have successfully:

• funded and developed FOXG1-specific mouse models 

• created a biobank of FOXG1 patient skin and blood samples, which we were able to turn into Induced Pluripotent Stem Cells and Mini Brain Organoids.

This took a long time, and we have all been patiently (sort of) waiting to get to the fun part. 

Now, we start Phase 2 and 3: Studying and Screening Drugs and Therapies on these models. 

What are we studying?

• How FOXG1 mutations affect brain circuits, different brain cells and human biology. What can we target to cure our children?

• What downstream genes are affected by FOXG1; are any of them fixable?

• What biomarkers can we find to test drugs against? Can we connect these biomarkers to clinical endpoints in our children? 

• When we screen drugs, how do they affect protein expression, functional assays and downstream targets?

What are we screening? 

• Small molecule drugs. Here’s a success story in a similar disease.

• Antisense therapies. Here’s a success story in a similar disease. 

• Gene therapies. Here’s a success story in a similar disease. 

We are also converting Astrocytes to Neurons:

In this breakthrough discovery, scientists at UCSD found a fairly simple way to convert astrocytes into neurons. These scientists were further stunned to see that when this treatment was given to Parkinson’s mice, movement disorder symptoms reversed and did not come back for the entire life of these mice. We know that FOXG1 syndrome leads to neuronal death and thus increasing the amount of neurons could reverse major symptoms. Dr Alysson Muotri, whose lab is luckily at UCSD, will be collaborating with these scientists to conduct similar experiments on FOXG1 astrocytes and brain organoids. 

Our goal in 2021 is to find both short-term drugs we can give our children today, as well as longer term solutions like ASO’s, gene therapies and other novel and emerging therapies. 

We’ve assembled a top tier FOXG1 Science Team to collaborate to achieve these goals:

High Throughput Screening

1. Houart Lab, King's College  - High throughput screening of small molecules on zebrafish 

2. Stemonix - A contract research organization conducting high throughput screening of small molecules, vitamins and herbs on neurospheres

3. Bedwell lab, University of Alabama - Screening ~200 primary, validated, non-cytotoxic hits to suppress nonsense mutations in cell lines

Targeted Screening (low-throughput)

1. Muotri Lab, UCSD - Screening of small molecules, antisense therapies, RNA therapies and gene therapies on neurospheres, IPS lines and organoids. Also characterizing/phenotyping these models

2. Lee lab, University at Buffalo - Screening of small molecules, antisense therapies, RNA therapies and gene therapies on mouse models. Also characterizing/phenotyping these models

3. Malamaci lab, SISSA - Developing RNA therapies for screening on IPS lines and mouse models 

1. Creyon Bio - Developing targeted antisense therapies to screen on organoids and mouse models

2. Meyer lab, Nationwide Childrens - Developing gene therapy approaches and new in vitro model systems; screening small molecules and looking at the mechanisms (protein expression, downstream targets) on IPS lines and mouse models

The collaboration within this esteemed team of scientists and labs will enable us to find a basket of solutions to cure FOXG1 syndrome.

WE NEED ALL HANDS ON DECK TO FUND THIS SCIENCE NOW!

We’re often told that we have accomplished more in these last three years than most organizations do in ten. As a community, we all pulled together and raised nearly $2 million to launch the critical Phase One projects. We couldn’t have done this without everyone’s fundraising support. 
Now, it’s time for our next push - we need to raise another $1.5 million in the next six months to screen and test potential therapies. We need all hands on deck to come together and move mountains for our children. Here are a few things you can do:

• Please donate here. 

• Ask your friends and family to help us reach this important goal

  • We’ve added the option to Donate Stock

• Buy your holiday presents at our store (more items coming very soon!).

• Create a Facebook fundraiser. Let followers know we need all hands on deck to get to clinical trials! 

  • If you can, offer to MATCH donations up to an amount.  

• Buy toys and all special needs items for children through our Amazon Affiliate program on our website.

• Go to smile.amazon.com every time you make any purchases on Amazon and set FOXG1 Research Foundation. Tell your friends and family to do this too! 

Thank you for supporting us on this journey.

And stay tuned as we have more exciting announcements coming this month!!

With much gratitude,

The FOXG1 Research Foundation Team