Grant Award Details
Grant Application Details
- Drug Development for Autism Spectrum Disorder Using Human Patient iPSCs
We will use human patient induced pluripotent stem cell (hiPSC)-based models to screen for a drug that activates a transcription factor critical to the treatment of Autism Spectrum Disorder (ASD).
Our goal is to develop a small molecule to treat Autism Spectrum Disorder (ASD), which currently affects 1/68 children born in the USA. Currently, there is no effective treatment.
Major Proposed Activities
- Assay Development for Drug Screening: Generate and characterize "disease-in-a-dish" models using hiPSCs generated from MEF2C Haploinsufficiency Syndrome patients, a form of ASD (month 1 - month 6).
- High-throughput Screening: Screen for hit-to-lead compounds that upregulate MEF2 activity by reporter-gene assay (month 3 - month 9).
- Efficacy Evaluation of Hits: Evaluate candidate therapeutics using ASD patient hiPSC-derived neurons (month 10 - month 18)
- Drug Optimization - 1) Perform additional SAR and optimization, and 2) Perform additional CNS permeability studies and initial PK (month 18 - month 24).
- Develop a Target Product Profile (month 21 - month 24). 1) Using the standard CIRM form, a TPP will be formulated for treatment of the MEF2C Haploinsufficiency Syndrome (MCHS) type of ASD.
Recent studies show that MEF2C activity not only affects MCHS but also other forms of ASD because MEF2C drives the activity of other ASD-related genes. Thus, while we are developing a treatment for the MCHS form of ASD, in fact MEF2 activator drugs may prove effective for a much large group of ASD patients. ASD is now reported to occur in 1 in every 68 births in both CA and the USA, so the benefit to the ASD community is potentially immense.