Based on ‘hope and love,’ UB celebrates opening of FOXG1 Research Center

The FOXG1 Research Foundation cuts the ribbon at the FOXG1 Research Center opening ceremony at UB.

By TOM DINKI

Hope and love aren’t often mentioned in the same breath as scientific research, but they’re exactly what UB’s FOXG1 Research Center (FRC) was founded on. 

“Love for every individual living with FOXG1 syndrome and other neurodevelopmental disorders, as well as their caregivers, and hope that we can find a cure for FOXG1 syndrome and related disorders on the basis of scientific discoveries we are making,” Soo-Kyung Lee, director of the FRC and the parent of a child with FOXG1 syndrome, told a crowd gathered to celebrate the center’s official opening Tuesday. 

The occasion included a ceremonial ribbon cutting and science symposium in the Buffalo Room of Capen Hall, as well as a tour of the Cooke Hall lab where the center’s researchers are developing a promising viral gene therapy against the rare disorder.

“This research center really represents a bold step forward, not only for the University at Buffalo but for the future of science,” said Robin Schulze, dean of the College of Arts and Sciences. “The center means we are that much closer to finding a cure for the neurodevelopmental disorder FOXG1 syndrome. Today’s ribbon cutting clears the way for innovative research and creative collaborations.”

The center is led by Lee, Empire Innovation Professor and Om P. Bahl Endowed Professor in the Department of Biological Sciences, College of Arts and Sciences, and her husband, Jae Lee, professor of biological sciences.

The Lees’ teenage daughter, Yuna, is one of only about 1,000 people in the world diagnosed with FOXG1 syndrome. It’s caused by a mutation of the FOXG1 gene, one of the most important genes for early brain development, and causes cognitive and physical disabilities, as well as life-threatening seizures. Those affected require 24/7 care.  

Soo-Kyung Lee (seated, left) and Jae Lee (right) listen to speakers during the ceremonial ribbon cutting for the FOXG1 Research Center. Photo: Douglas Levere

Since Yuna was diagnosed in 2012, the Lees, who joined UB in 2019, have dedicated their careers to studying the disorder. They’ve found that the FOXG1 gene and protein remain active in mice after birth, providing hope that some symptoms can be alleviated, and hope that therapy of the FOXG1 gene may be transferable to more common disorders like autism and Alzheimer’s disease.

This new center will support the Lees’ ongoing development of a viral gene therapy. A postnatal injection of the therapy into day-old mice rescued abnormalities in parts of the brain responsible for language, memory and social interaction. Their goal is to begin human clinical trials as early as spring 2026, pending U.S. Food and Drug Administration approval.

“[The Lees’] groundbreaking viral therapy offers renewed hope for patients and families affected by this rare disorder. Their personal journey and unwavering dedication to this cause are truly inspiring,” said Venu Govindaraju, vice president for research and economic development, whose office is supporting the center. 

Govindaraju added that between the FRC and the National AI Institute for Exceptional Education — which will use artificial intelligence to assist children with speech and language disorders — UB is dedicated to addressing the unique challenges faced by individuals with disabilities.

“The potential of artificial intelligence in drug discovery and personalized medicine is immense,” he said. “As a leading scientific research community and our excellence in AI and life sciences, we are committed to exploring innovative approaches that can accelerate the development of effective treatments for FOXG1 syndrome and other neurodevelopmental disorders.”

The Lees take ribbon-cutting attendees on a tour of the research center in Cooke Hall. Photo: Douglas Levere

The FRC is also supported by the FOXG1 Research Foundation, where Soo-Kyung Lee is chief scientific officer. The foundation’s CEO, Nasha Fitter, who is also the parent of a child with FOXG1 syndrome, recalled first connecting with Soo-Kyung Lee via a Facebook group in 2017. 

“I honestly almost fell off my chair that we had a neuroscientist who was also a parent and no one had told me this,” Fitter said. “And then I learned that her husband was also a neuroscientist.”

Fitter and others co-founded the FOXG1 Research Foundation shortly after. She traced the organization’s rise, from its humble first symposium in 2018 to now having raised more than $7 million toward human clinical trials, and credited a large part of that success to its partnership with the Lees’ lab.

“They have built an entire gene therapy lab at the University at Buffalo. It is exceptional for an academic medical center to develop treatments,” Fitter said. “That does not usually happen at university campuses, and that is what is happening here.

“We’re literally creating the drug that will be given to our children in a clinical trial,” she added. “It’s a monumental step that this has happened in seven years.”

Jae Lee concluded the day by thanking children with FOXG1 syndrome for making their families whole.

“I feel we are closer to the finish line to find the cure for FOXG1 syndrome,” he said.

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

January Newsletter: Big Things in 2019

View the Full Newsletter in your bowser HERE

https://www.foxg1research.org/foxg1-patient-registry/

www.foxg1research.org/donate

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