Cure SMA is pleased to announce that we have extended our spinal muscular atrophy research program with the California Institute of Biomedical Research (CALIBR) with an additional $315,000 drug discovery grant.
This partnership first began in 2012, when we awarded $700,000 to Dr. Peter G. Schultz and his team for their drug discovery program, “Optimization of Small Molecules that Increase SMN2 Levels for the Treatment of Spinal Muscular Atrophy.”
Survival motor neuron (SMN) protein is critical to the function of the nerves that control our muscles. Individuals with spinal muscular atrophy don’t properly produce this protein at high enough levels, due to a mutation in the survival motor neuron gene 1 (SMN1). Individuals with SMA do have one or more copies of survival motor neuron gene 2 (SMN2), the SMA “back-up gene.” SMN2 makes only a small amount of functional SMN protein, so researchers are looking for ways to prompt this gene to make more protein.
One very promising therapeutic approach is small molecules, which are chemicals that can treat or cure a disease. The Schultz group previously discovered several different compound classes that enhance SMN protein levels. Our funding to CALIBR has been focused on turning these compounds into a useable drug through a process called medicinal chemistry.
Progress to Date
As with all our drug discovery grants, this program is overseen by the Cure SMA Translational Advisory Council (TAC), a committee of drug discovery and SMA experts. Funding for this project is provided after achieving a series of predetermined milestones, which are reviewed and approved by a sub group of the TAC convened specifically to oversee this program.
To date, the research team has completed the following:
- They have demonstrated that compound treatment elevates SMN protein levels in a severe mouse model of SMA.
- They have identified new related compounds, called analogs, that require less drug to increase SMN levels.
- They have identified new analogs with more drug reaching the brain.
Recently, we expanded our funding of this project to include a collaborative effort with Dr. Chien-Ping Ko of the University of Southern California. Currently, Dr. Ko and the team are testing compounds for benefit in a severe mouse model of SMA. They will be assessing weight gain, motor function, survival, and motor neuron morphology at synapses in the central nervous system and at the muscle.
Next Steps for New Funding
The new goals of the project, which will also be funded through a series of predetermined milestones, focus on continuing to optimize compounds in order to identify a drug candidate suitable for human testing. These goals include demonstrating a survival benefit in a severe model of SMA, further enhancement of brain exposure, and optimization of safety and selectivity of the lead compounds.
These optimized compounds will hopefully lead to a clinical development candidate. The candidate would then undergo the series of studies required for an Investigational New Drug (IND) application, the first step to obtaining FDA approval for a human clinical trial.
Pictured above: a specialized robot that is used in drug discovery screening.
Cure SMA Drug Discovery Strategy
Developing a treatment and cure for SMA is the driving force behind Cure SMA, and the goal of our research model.
Drug discovery, the second stage of that research model, converts basic research ideas into new drug candidates that can be tested in clinical trials. Our unique research model minimizes the most common challenges of drug discovery by building a diverse “pipeline” of drug candidates. Ten years ago, we had just two potential drugs in the pipeline. Five years ago, we had four. Today we have seventeen, including seven now in clinical trials. Cure SMA has funded over half of these programs.
While there is real promise in the research landscape right now, which gives us great reason for hope, we know that much work remains to be done. There’s a pressing need for continued and growing investment in drug discovery, to respond to the complexities of the process and lead into clinical trials. This is why we aggressively invest in promising programs like the CALIBR program.
Funding for the CALIBR program is supported by a special gift from The Michael and Chandra Rudd Foundation. Funding for the USC expansion is supported by a special gift from the Dhont Family Foundation.