News
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 known in the industry as innovators as we focus 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. Here are the FOXG1 Research Foundation highlights from 2023 and goals for 2024.
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
2022 Impact Report
2022 Research Highlights (see details below)
Breakthrough gene therapy results showing rescue of FOXG1 brain structure, behavior, memory and cognition symptoms in animal models
Positive results on initial compound drug screens to identify molecules to increase FOXG1 levels; now moving forward to larger screens
Never-before understanding of FOXG1 biology uncovered from six FOXG1 patient human cell lines and mouse models
Successful testing of guide RNAs to increase FOXG1 expression with a CRISPRa Cas-9 system
Discovered ASO sequences (antisense gene therapy) to modulate FOXG1 expression; testing initiated with Creyon Bio
FOXG1 data package presented to several biotech companies with high interest
2022 marked five years of the FOXG1 Research Foundation.
Our work brings us closer to successful therapeutics for every child, while supporting families along this difficult journey. We continue to be one of the most innovative foundations in the rare disease space, focused on three equally critical areas: FOXG1 science, FOXG1 patient data, and FOXG1 patients and community. From gene therapy to rescuing a FOXG1 family in the Ukraine, this year marks our biggest breakthroughs in all three areas.
Our greatest purpose is to end the suffering of children with this terrible disease. Our community is mourning the loss of 11 children in 2022/23 alone. We must stop this from happening. We are grateful for this incredible team working collectively to advance this goal, and to our donors who enable this work.
2022 Research Highlights (see details below)
Breakthrough gene therapy results showing rescue of FOXG1 brain structure, behavior, memory and cognition symptoms in animal models
Positive results on initial compound drug screens to identify molecules to increase FOXG1 levels; now moving forward to larger screens
Never-before understanding of FOXG1 biology uncovered from six FOXG1 patient human cell lines and mouse models
Successful testing of guide RNAs to increase FOXG1 expression with a CRISPRa Cas-9 system
Discovered ASO sequences (antisense gene therapy) to modulate FOXG1 expression; testing initiated with Creyon Bio
FOXG1 data package presented to several biotech companies with high interest
2022 Foundation Highlights
Hosted first-ever FOXG1 Syndrome Parents Conference (in-person and virtual) with parents, families, clinicians, scientists from all over the world
Hosted third FOXG1 Syndrome Science Symposium (in-person and virtual) with a consortium of global scientists collaborating on the path to a cure
Publishing first 100 patient natural history study of FOXG1 syndrome patients
Launched successful rescue operation of FOXG1 family trapped in the Ukraine; created fundraising campaign to help rebuild their lives in Poland
Asked to speak on multiple podcasts and industry events, continued to be called “innovators” and “leaders,” assisting many other rare disease foundations
Launched FOXG1 Research Foundation España
Raised over $1,000,000 globally in 2022 ($6M to-date)
2022 Funding and Research Details (View Research Projects)
Gene Therapy:
Breakthrough AAV9 gene therapy preclinical trial results with two promoters that successfully rescue FOXG1 brain structure, behavior, memory and cognition symptoms in animal models. Next step is toxicology studies as we begin an IND application. If successful, we will be in clinical trials within two years
Further testing of additional promoters at the Lee Lab - FOXG1 Center of Excellence that may more-effectively drive FOXG1 in specific cells
Funding Dr. Goichi Miyoshi at Gunma University Graduate School of Medicine to identify cells and circuits responsible for the manifestation of FOXG1 Syndrome in the brain and test a specialized rescue strategy
Initiated the development of a “rescue” mouse model to be used to determine the cell types and timelines that are key to restoration of FOXG1 symptoms
RNA Therapies
RNAi/a therapies - Identified multiple sequences and conducted experiments that both upregulate and downregulate FOXG1 gene expression via RNAa and RNA mechanisms in human neurons. Now stabilizing sequences and testing for efficacy and toxicity in additional patient derived human stem cells and animal models. If successful, we are within 3 years of clinical trials
ASO therapies - Identified a group of ASO molecules that upregulate FOXG1 gene expression. Using a proprietary platform, we are testing these ASO’s to find the most optimal ones. If successful, we could be in clinical trials in 2024
Drug Repurposing and Label Expansion
Screening of 4,000 compounds to increase FOXG1 expression led to 40 FDA-approved drug candidates found through Rarebase neuroscience platform
Screened ~150 small molecules on our zebrafish platform
Created neuronal assets and investigated several neuronal platforms, screens to start within next few months
Initiating c-elegans genetic screen in FOXG1 worm models to identify pathways that can compensate for the loss of FOXG1
CRISPRa Therapy
Identified a number of lead sgRNA and dCas9-effector combinations for upregulating FOXG1 expression in HEK293 cells, healthy NSC, and in patient iPSC-derived NSC
Next steps are to check for potential off-target effects and ability to rescue neuronal phenotypes before embarking on toxicity studies to assess if this is an effective modality for FOXG1
Genetic Model Characterization Work
Analyzed brain structure and behavioral deficits in three mouse models, developed insight into impact of DNA binding affinity; continuing to research additional models and publication underway
Confirmed the presence of FOXG1 mutations and otherwise normal chromosomal composition in six patient iPSC lines; seeing protein expression changes
Funded Dr. Jeanne Paz at Gladstone Institute to characterize the electrophysiology and seizures in our mouse models. This will identify where in the brain seizures are forming as well as identify any unique brain signatures
Confirmed the formation of smaller brain organoids from two patient lines compared to healthy controls
FOXG1 Patient Data
Enrolled >100 children and adults with FOXG1 syndrome into our natural history study, hosted on the Ciitizen platform, the most comprehensive and innovative natural history study for FOXG1 syndrome patients
Longitudinal medical record collection for all participants, averaging ~1200 pages of data from ~5 institutions, per participant - this totals 618 years of data reviewed
Uncovered information on demographics, comorbidities, common medications, exam findings, therapeutic procedures, developmental milestones; data will assist in identifying primary and secondary endpoints in clinical trials
Two years of FDA validated surveys completed by the first 50 participants, evaluating developmental milestones, behavior, and sleep
Three breakthrough manuscripts in preparation that include clinical data about FOXG1 syndrome
Continued to build global FOXG1 Patient Registry encompassing ~500 unique patient mutations
FOXG1 Research Models / Assets Created
6 human stem cell lines and 16 patient fibroblasts containing unique mutations available in FOXG1 Coriell global repository
Five CRISPR corrected patient stem cells stored in FOXG1 In-House Cellular lab
Inducible rescue mouse line underway at Lee Lab - FOXG1 Center of Excellence
5+ patient mouse models being characterized and stored at Lee Lab - FOXG1 Center of Excellence; publication underway
Accessible raw patient survey and natural history data available at FOXG1 Data Center and Ciitizen
2023 Goal: Drive the science to clinical drug development
Continue progress towards clinical trials for gene therapies
Accelerate each project by funding additional post-docs; continue funding scientific team
Fund further understanding of FOXG1 symptoms, such as electrophysiology characterization in mouse models
Compile arsenal of repurposed drugs that can be prescribed by individual physicians
Continue to expand upon patient registry and natural history study work
Raise reserves for clinical drug development
Partner with biopharma to include FOXG1 syndrome in their pipelines
Host continued parent and science conferences
Be there for our community through resources, encouragement and love
Funding:
FOXG1 Research Foundation 2022 Source of Funds
