gene therapy case study buffalo

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

Promising gene therapy for FOXG1 syndrome

Treatment reverses brain abnormalities in mice, a step toward human clinical trials.

A viral gene therapy developed by University at Buffalo researchers has reversed some brain abnormalities in infant mice with FOXG1 syndrome, a significant step toward one day treating children with this severe neurodevelopmental disorder.

This mediated delivery of the FOXG1 gene via adeno-associated virus 9 (AAV9) is detailed in a study published June 5 in Molecular Therapy Methods & Clinical Development . A postnatal injection of the therapy in day-old mice rescued a wide range of abnormalities, the study found, including in parts of the brain responsible for language, memory and social interaction.

"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," says Soo-Kyung Lee, PhD, Empire Innovation Professor and Om P. Bahl Endowed Professor in the UB Department of Biological Sciences, College of Arts and Sciences, who led the study along with her husband, Jae Lee, PhD, professor in the department. "This research asserts the therapeutic relevance of our approach in postnatal stages, which is a critical time frame for intervention."

The Lees' teenage daughter, Yuna, was diagnosed with FOXG1 syndrome at the age of 2. The researchers have since established themselves as leading experts on the disorder and are the principal investigators of UB's FOXG1 Research Center (FRC). The center, which launched earlier this year, as well as this recent study, are supported by the FOXG1 Research Foundation.

The study was co-led by Kathrin Meyer, PhD, principal investigator at Nationwide Children's Hospital in Columbus, Ohio. Other contributions represent the University of Pennsylvania and Samsung Medical Center in Seoul, South Korea.

Reversing structural abnormalities

A master regulator gene, FOXG1 is one of the most important genes for early brain development and its impairment can result in profound brain structure abnormalities.

The Lees previously established that the FOXG1 gene and protein remain active in mice after birth, so they wondered if restoring FOXG1 levels could reverse some of the abnormalities associated with FOXG1 syndrome.

These abnormalities include failure to fully develop the corpus callosum, the bundle of nerves that connect the brain's two hemispheres and help integrate sensory and motor information with social interaction, executive function and language.

It's thought that correcting the corpus callosum postnatally would be extremely difficult given that it develops before birth, but, when injected into mice postnatally, the Lee team's viral gene therapy reconnected the callosal axons and restored the callosal nerves, substantially recovering the corpus callosum.

The therapy also increased the size of the dentate gyrus, the primary gateway for input formation into the rest of the hippocampus that is crucial for memory. This is one of only a few areas of the brain that continues to produce new neurons as mammals age into adulthood, making it a crucial target for postnatal treatments.

In addition, the therapy rescued areas of the brain related to signal speed between neurons.

Oligodendrocytes are the cells primarily responsible for myelination, the process of insulating nerves so they can transmit information rapidly. Brains with FOXG1 often have high numbers of oligodendrocyte precursor cells (OPC) yet delayed myelination.

According to the study, the therapy normalized the number of OPCs while restoring myelination.

The study provides a solid foundation for advancing the gene therapy toward human clinical trials, researchers said.

"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 compound towards human clinical trials, hopeful that we can extend these breakthroughs to benefit children with FOXG1 syndrome."

• Gene Therapy
• Nervous System
• Psychology Research
• Birth Defects
• Neuroscience
• Brain Injury
• Child Development
• Learning Disorders
• Sudden infant death syndrome
• Gene therapy
• Tourette syndrome
• Electroconvulsive therapy
• Chronic fatigue syndrome
• Down syndrome
• Attention-deficit hyperactivity disorder

Story Source:

Materials provided by University at Buffalo . Original written by Tom Dinki. Note: Content may be edited for style and length.

Journal Reference :

• Shin Jeon, Jaein Park, Shibi Likhite, Ji Hwan Moon, Dongjun Shin, Liwen Li, Kathrin C. Meyer, Jae W. Lee, Soo-Kyung Lee. The postnatal injection of AAV9-FOXG1 rescues corpus callosum agenesis and other brain deficits in the mouse model of FOXG1 syndrome . Molecular Therapy - Methods & Clinical Development , 2024; 101275 DOI: 10.1016/j.omtm.2024.101275

Cite This Page :

Explore More

• Saturn's Moon Titan Has Thick Insulating Crust
• 'Well-Man' Thrown from Castle 800 Years Ago
• Dandelion-Shaped Supernova and Zombie Star
• Gut Bacteria Transfer Genes to Beat ...
• Tiny Electric Currents May Cut Skin Infections
• Grain-Sized Soft Robots for Drug Delivery
• PFAS: US Drinking Water Contamination
• Chronic Pain Predicted Within 3 Days of Injury
• Electric Cars: Long-Lasting Renewable Batteries
• Wildfires Becoming Faster, More Dangerous

Trending Topics

Strange & offbeat.

• Professional Staff Senate >
• PSS News >
• UB biologists awarded $1.5 million to study gene therapy for FOXG1 Syndrome

UB awarded $1.5 million to study gene therapy for FOXG1 Syndrome

The daughter of Soo-Kyung Lee and Jae Lee, above, suffers from the rare genetic disorder.  Credit: Douglas Levere, University at Buffalo

The grant, from the Simons Foundation Autism Research Initiative, could help benefit people suffering from the rare genetic brain disorder

By Mary Durlak

Release Date: April 3, 2023

BUFFALO, N.Y. — A $1.5 million grant has been awarded to University at Buffalo researcher Soo-Kyung Lee to study the rare neurodevelopmental disorder FOXG1 Syndrome. Lee, Empire Innovation Professor and Om P. Bahl Endowed Professor in the Department of Biological Sciences, received the award from the Simons Foundation Autism Research Initiative on March 23.

“I am humbled and honored to receive this grant,” said Soo-Kyung, “and we hope to find a way to alleviate symptoms in people with FOXG1 Syndrome or other disorders in which FOXG1 plays important roles, such as autism spectrum disorder and schizophrenia.”

The grant will fund a three-year study – “Development of therapeutics for FOXG1 syndrome using patient-specific human iPSC and mouse models” – to investigate possible therapies to mitigate FOXG1 Syndrome. It’s a genetic disorder on which Soo-Kyung and Jae W. Lee, also a UB scientist, have focused their research since their daughter Yuna was diagnosed with it at 2 years old .

FOXG1 Syndrome is caused by a spontaneous mutation in the FOXG1 gene, which is a critical gene for forebrain development. Symptoms can range from autism (considered a less severe effect) to nonverbal, non-ambulatory symptoms that may be accompanied by seizures and feeding problems as well as developmental delays.

Soo-Kyung and Jae had focused their earlier research on master regulator genes – Jae in metabolism and diabetes, and Soo-Kyung in brain development. FOXG1 is a master regulator gene that regulates all the other developmental processes that allow for normal forebrain development – development of the cortex, the hippocampus, the striatum, and the corpus callosum, which connects the left and right brain.

“We didn’t have much hope for gene therapy in the beginning,” said Jae, UB professor of biological sciences.

Unexpected breakthrough

With previous funding from the National Institutes of Health and the  FOXG1 Research Foundation  – a global organization accelerating research to cure the syndrome and related neurological disorders – the Lees have deepened their understanding of the mechanisms of FOXG1. They realized that the gene continues to function after birth, which gave them hope.

Then they had an unexpected success with viral gene therapy – a way of providing potentially beneficial restoration of FOXG1 levels – in mice with FOXG1 Syndrome. Such mice show symptoms that replicate the symptoms in humans, including symptoms of autistic disorders that affect learning, memory, social interaction ability and movement.

Last year, the researchers took the gene therapy vector encoding a properly functioning FOXG1 protein and injected it into a strain of mice born with FOXG1 Syndrome. The mice received the gene therapy postnatally when they were one day old. The results astonished the Lees.

“We were able to rescue functions,” said Jae. “They behaved like normal mice.”

Results to date suggest that, done early enough, even structural deficiencies can be mitigated. The aim of the funded research is “really a deep analysis of what is going on so that we can develop effective and safe therapeutic strategies,” said Jae.

Four strains of mice with FOXG1 Syndrome with varying degrees of severity will be used to explore how the gene therapy affects them if it is administered postnatally. Researchers will look at its effects on brain structure, cells, behavior and how long after birth the potential for therapeutic benefit exists.

“We know we cannot go back and undo the damage to people who have this condition,” said Jae. “But we are interested in any modifications to the effects of the disease that may increase patients’ quality of life. Now, of course, we hope that our daughter may benefit from it, along with other people suffering from disease.”

Media Contact Information

Media Relations (University Communications) 330 Crofts Hall (North Campus) Buffalo, NY 14260-7015 Tel: 716-645-6969 [email protected]

University News

• 10/25/24 UB Center for the Arts Presents Art in the Open
• 10/25/24 Unlocking the mysteries of language learning
• 10/25/24 Helping transfer students succeed at UB
• 10/25/24 Shedding light on severe MS
• 10/24/24 Dental dean reflects on first 18 months on the job
• 10/24/24 Zodiaque celebrates 50 years of dance
• 10/24/24 Cannabis policy shift to public health approach urged
• 10/24/24 Honoring a pioneer with equitable action
• 10/24/24 UB launching new summer STEM program for refugee and underprivileged teens in Buffalo
• 10/24/24 Media Advisory: UB to spotlight Diana Aga’s forever chemical research at new symposium
• 10/24/24 Event aims to strengthen Buffalo’s support for equitable urban agriculture
• 10/24/24 Gene named for mythical Irish land could aid muscle function after traumatic nerve injuries
• 10/23/24 Researchers show why cannabis policies should shift to a harm reduction, health promotion approach
• 10/23/24 Exhibit to feature work of textile artist Guzmán Capron
• 10/23/24 Pollinator Lounge coming to South Campus
• 10/23/24 Faculty, staff share their UB giving stories
• 10/23/24 Severe MS: Researchers report findings from some of the first studies conducted on patients with this rare form of the disease
• 10/22/24 Where are Western York’s AEDs?
• 10/22/24 Why do we love carbs?
• 10/22/24 Four UB professors named APS fellows
• PSS Pledge to Recent Social Tensions

Did you know there are special offers and promotions for PSS members? Find out more!

Upcoming Events

• 2/4/22 Ergonomics for Office & Home workspaces
• 10/9/24 Strengthening Communication with Your Manager - UB Employee Assistance Program (EAP)
• 10/9/24 Lessons Learned from the Pandemic at Work: Panel Discussion

Learn CPR and AED use with the American Heart Association

Cardiopulmonary resuscitation (CPR) is an emergency procedure that can help save a person’s life if their breathing or heart stops. The  Recreation and Wellness Committee  is dedicated to promoting and maintaining the latest health and safety policies across UB. 

Please note : If someone on a UB Campus goes into cardiac arrest and emergency services need to be called, call University Police at 645-2222.  Do not  call 911 if you are on a UB Campus.

Hands-Only CPR plus AED – Female Body Example

Hands-Only CPR plus AED – Male Body Example