Cure SMA has awrded a $50,000 Drug Discovery Grant to Brigham and Women’s Hospital researcher Kevin Hodgetts, PhD, at the Lab for Drug Discovery in Neurodegeneration for his project “Development of a Drug to Increase SMN2 Transcription.”
is part of a total $704,000 that is now being awarded in smaller grants as New Drug Discovery funding.
Cure SMA established the grant program to convert what the scientific and medical community has learned through basic research on the causes of spinal muscular atrophy (SMA) into new drug candidates.
According to the press release, Hodgetts and his research colleagues are looking into two different series of chemical platforms to analyze whether they might be of use to increase SMN2 transcription, one of the faulty proteins responsible for the development of the disease. This approach could potentially be used in combination with other treatments to increase SMN levels, like SMN2 splicing modulators.
Earlier SMA research has focused on increasing SMN protein levels by targeting the underlying genetics of SMA. The goal is to trigger the production of more SMN protein by replacing, or correcting, SMN1 – or by modulating SMN2, the low-functioning back-up gene. But another potential way to increase SMN levels is to increase transcription of the SMN2 gene – a process by which the information contained within the DNA is copied into messenger RNA (mRNA) and ultimately transformed into proteins.
The project’s purpose is to optimize a compound that already increases transcription of SMN2 to have higher drug-like properties, making it more suitable for pre-clinical evaluation.
Hodgetts and his team will develop an acceptable formulation and improve solubility of the main compounds so that they can be more easily administered in animal models to study their efficacy.
Elliot Androphy, Ph.D., was the first to identify the compounds now being studied and he is now collaborating with Hodgetts in this project.