Cure SMA Awards $50,000 Drug Discovery Grant to Kevin Hodgetts, PhD, at The Lab for Drug Discovery in Neurodegeneration at Brigham and Women’s Hospital
Cure SMA has awarded a $50,000 drug discovery grant to Kevin Hodgetts, PhD, at The Lab for Drug Discovery in Neurodegeneration at Brigham and Women’s Hospital. The award is for the project, “Development of a Drug to Increase SMN2 Transcription.”
Individuals with SMA don’t produce survival motor neuron (SMN) protein at high enough levels due to a mutation in the survival motor neuron 1 (SMN1) gene. Much of the early research into SMA has focused on increasing the levels of SMN protein by targeting the underlying genetics of SMA. The goal is to prompt the body to make more SMN protein by replacing or correcting SMN1, or by modulating SMN2, the low-functioning SMA “backup gene.”
Another potential way of increasing SMN levels is to increase transcription of the SMN2 gene. Transcription is the process by which the information in DNA is copied into messenger RNA (mRNA) for protein production. This process can be thought of in terms of an engine, where increasing or decreasing transcription is akin to turning a gene on or off. Dr. Hodgetts and his team are investigating two distinct series of chemical platforms, to see if they might be used to increase SMN2 transcription.
The objective of this project is to optimize a compound that already increases transcription of SMN2 to have more drug-like properties suitable for pre-clinical evaluation. They will develop acceptable formulations and improve solubility of the lead compounds to enable them to be administered more easily for mouse model efficacy studies. Dr. Hodgetts and his team are working in collaboration with Elliot Androphy’s lab. Dr. Androphy was first to identify the compounds now being studied.
Researchers believe this approach could be used alongside other treatments that boost SMN levels by other mechanisms, such as SMN2 splicing modulators. This would open up yet another possible avenue for combination therapies, which are needed to develop treatments for all ages, types and stages of SMA.
Drug Discovery Funding
This grant to Dr. Hodgetts is part of $704,000 in new drug discovery funding that we’re currently announcing. Drug discovery converts what we have learned about the causes and biology of SMA through basic research into new drug candidates that can be tested in clinical trials.