Cure SMA has awarded a $50,000 drug discovery grant to Barrington Burnett, PhD, at Uniformed Services University of the Health Sciences. The award is for the project, “Slowing SMN degradation to treat SMA.”

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 target the SMN protein directly. Dr. Burnett and his team are investigating ways to slow the degradation of SMN protein, causing it to stay around for longer length of time and effectively increasing the overall levels of SMN protein in cells.

The goal of this project is to characterize and validate a novel SMN protein modulator for possible treatment of spinal muscular atrophy. This modulator regulates the degradation of the SMA protein. The team will utilize cell-based assays and animal models to investigate safety, efficacy and selectivity of a new compound identified using a high throughput screen that modulates SMN protein degradation. The project aims to help develop molecules that possesses a unique mode of action to treat SMA.

Researchers believe this approach could be used alongside other treatments that boost SMN levels by other mechanisms, such as SMN2 splicing modulators, allowing the body to both produce more protein and make that protein last longer. 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. Burnett 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.