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Drug Repurposing and the YWHAG Genetic Mutation
Welcome to the YWHAG Foundation’s dedicated page on drug repurposing and its potential to provide new treatment options for those affected by the YWHAG genetic mutation. Here, we unpack our current project in the space as we aim to explain what drug repurposing is, how it works, and why it holds promise for addressing the unique challenges posed by the YWHAG genetic mutation.
Research Update: Observational Study for Drug Repurposing Through the Foundation’s drug repurposing efforts, Lovastatin was identified as a promising candidate after small-molecule screening and RNA sequencing studies showed it may help shift abnormal gene expression toward a more typical pattern in YWHAG-mutant cells . These early findings provided an important starting point and helped guide the next phase of research. Why Lovastatin Continues to Be of Interest Lovastatin is a well-established medication that has been safely used for decades. Beyond its role in cholesterol management, it also affects key signaling pathways in the brain, including the Ras/MAPK pathway, which is relevant to YWHAG biology . Studies in related neurological conditions, such as Fragile X syndrome and Neurofibromatosis Type 1, have shown that lovastatin is well tolerated and may have positive effects on cognition and behavior. These findings further support its potential relevance in YWHAG. What We Are Learning Now While lovastatin has not yet been formally studied in individuals with YWHAG, early laboratory data suggest it may help normalize disrupted cellular signaling. To build on this, the Foundation is now focused on collecting real-world data through an Observational study coinciding with the Natural History Study. Role of the Natural History Study As part of the Natural History Study, families and clinicians are able to share information about medications being used in routine care including lovastatin. This observational effort allows researchers to better understand: Changes in seizure activity Developmental progress Behavioral patterns Importantly, this study does not involve prescribing medication. Instead, it captures real-world experiences that can help guide future clinical research and trial design. Why This Matters For rare conditions like YWHAG, building meaningful data takes time and community participation. Every shared experience helps strengthen our understanding and move the field forward. This work represents an important step toward: Identifying potential treatment strategies Prioritizing future clinical studies Accelerating progress toward targeted therapies Interested in Participating? If you are currently using, considering, or simply interested in contributing to this observational effort, we would love to hear from you. Please reach out to us at: info@ywhagfoundation.org Supporting Conversations with Your Care Team We recognize that navigating potential treatment options can feel overwhelming, especially when discussing emerging research with your child’s care team. To help support families in these conversations, the Foundation has developed a clinician-friendly handout that summarizes: The rationale behind drug repurposing in YWHAG Why lovastatin has emerged as a potential candidate Evidence from other rare and neurodevelopmental disorders where it has been safely and effectively used Key considerations for discussion with healthcare providers This resource is designed to be informative and easy to share with primary care physicians and specialists. It is not intended to replace medical guidance, but rather to help facilitate more informed and productive conversations between families and their care teams.
STATUS REPORT SPRING 2026
Collaborative Efforts with Transcriptabio (Formerly Rarebase)
We are proud to collaborate with Transcriptabio, a cutting-edge public benefit biotechnology company and rare disease patient and research organization to enhance our drug repurposing efforts. Transcriptabio is utilizing induced pluripotent stem cells (iPSCs) to perform drug repurposing research for the YWHAG Foundation.
Image courtesy of Transcriptabio (Formerly Rarebase)
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Faster Development
Since the safety profiles of these drugs are already established, the timeline for bringing them to clinical use for a new indication is shorter compared to developing a new drug from scratch.
WHAT IS DRUG REPURPOSING?
Drug repurposing involves finding new therapeutic uses for existing medications that are already approved for other conditions. This approach provides a wide range of considerable advantages:
Cost-Effective
Drug repurposing can reduce the high costs associated with early-stage drug development, as many steps in the drug discovery process are bypassed.
Innovation
By exploring new applications for existing drugs, researchers can uncover innovative treatments for diseases that currently lack effective therapies.
The YWHAG Genetic Mutation
The YWHAG genetic mutation affects the 14-3-3 gamma protein, which is crucial for various cellular processes including signal transduction, cell cycle control, and apoptosis. This mutation is associated with severe neurological disorders, epilepsy, and developmental delays. Due to the rarity and complexity of this condition, developing targeted treatments has been particularly challenging.
Furthermore, the YWHAG Genetic mutation results in a haploinsufficiency meaning there is only one functional copy of the gene, which results in insufficient protein production for normal function. Enhancing the performance of this working copy is a method to increase the production of the necessary proteins, 14-3-3 gamma. The goal of the drug repurposing project is to find an already approved drug that upregulates or increases production of the wild type or good protein.
Why Drug Repurposing for YWHAG Mutation?
The YWHAG genetic mutation affects the 14-3-3 gamma protein, which is crucial for various cellular processes including signal transduction, cell cycle control, and apoptosis. This mutation is associated with severe neurological disorders, epilepsy, and developmental delays. Due to the rarity and complexity of this condition, developing targeted treatments has been particularly challenging.
iPSCs in Drug Repurposing
iPSCs are cells that can be reprogrammed to an embryonic-like state and then differentiated into various cell types, including neurons affected by the YWHAG mutation. This innovative approach allows researchers to:
Model Disease Mechanisms
By creating patient-specific iPSCs, scientists can study the YWHAG mutation in a controlled environment, gaining insights into the disease mechanisms.
Test Drug Efficacy
iPSCs provide a platform for high-throughput screening ( aka HTS; a method used in drug discovery and other fields of biology and chemistry to quickly conduct millions of chemical, genetic, or pharmacological tests) of existing drugs to evaluate their efficacy in correcting the cellular defects caused by the YWHAG mutation.
JOIN US IN OUR CAUSE
Drug repurposing offers a promising path toward finding effective treatments for the YWHAG genetic mutation. The YWHAG Foundation remains committed to advancing our current Transcriptabio Drug Repurposing program as well as developing further research projects– bringing hope and potential relief to those affected by this rare genetic disorder. Thank you for your continued support and interest in our mission!