Cure SMA Awards $304,000 Drug Discovery Grant to Livio Pellizzoni, PhD, at Columbia University

Cure SMA has awarded a $304,000 drug discovery grant to Livio Pellizzoni, PhD, at Columbia University. The award is for the project, “Pharmacological Inhibition of p38αMAPK as a Candidate Therapeutic Approach for SMA.”

About the Project

Dr. Pellizzoni and his colleagues at Northwestern University have identified a novel cellular pathway, called p38αMAPK, that is altered in SMA and may directly contribute to how the disease develops. For instance, SMN deficiency results in activation of p38αMAPK in mouse models of SMA. The goal of this project is to evaluate whether inhibiting this pathway may help treat SMA. An orally available p38αMAPK inhibitor is currently in advanced clinical trials for the treatment of Alzheimer’s disease and other neurological disorders. Researchers will be testing this compound in a mouse model of SMA, to see if it might also be useful in treating SMA. The results of this project may be used to support further pre-clinical and clinical development of this drug for use in SMA.

The Importance of Combination Therapies

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 SMN production, either by replacing or correcting SMN1 or by modulating SMN2, the low-functioning SMA “backup gene.” Many of these SMN-based approaches are already being tested in clinical trials.

Research has also revealed that a number of systems, pathways and processes, such as including p38αMAPK, are affected in SMA, and there may be additional ways to treat SMA that work on these other areas. And perhaps most crucially, these other approaches could be used in combination with approaches that work on SMN levels, allowing us to attack SMA from all sides and giving us the best chance of a comprehensive, effective treatment. This is particularly important as we seek to develop treatments for all ages, stages and types of SMA.

Driving Research to Attack SMA from All Sides

Recently, the Cure SMA Board of Directors developed a strategic plan for our SMA research funding, in collaboration with leading experts in the field. One outcome of this plan is a greater focus on developing combination drugs for SMA, in order to treat all stages and types of the disease. SMN enhancing approaches may be accentuated by combining them with drugs that target pathways that contribute to motor neuron death and/or muscle dysfunction, but act independently of SMN.

At past several SMA Researcher Meetings, Cure SMA has explored this important issue with the research community. The 2015 Researcher Meeting also includes information on our efforts to see what we might learn from the research being done in other related disorders. Work being done in ALS, Parkinson’s—and, this case, Alzheimer’s disease—could help inform many of the potential non-SMN approaches being studied. This could both accelerate the development of treatments for SMA, and provide us with the opportunity to help inform treatments for other diseases.

Drug Discovery Funding

This grant to Dr. Pellizzoni 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.

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