D
R
U
G
R
E
P
U
R
P
O
S
I
N
G
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.
STATUS REPORT SPRING 2024
As of spring of 2024 we are thrilled to report that our drug repurposing program has identified several promising candidates. Transcriptabio has converted the engineered induced pluripotent stem cells (iPSCs) into neurons and has verified their phenotype and baseline parameters. They are testing the lead drug candidates in these neuronal cell models, assessing gene expression and cell viability in response to treatments. This process aims to confirm the activity of drug candidates that increase YWHAG gene expression in wild-type neurons.
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)
.png)
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!