UPDATE (April 9, 2012): MDA and ALS Biopharma agreed to terminate this project in April 2012, when ALS Biopharma determined that it was unable to manufacture its HSP70-based compound in a pure enough form to meet study standards. The ability to reliably produce the compound in sufficient quantity and quality for testing purposes was one of a number of milestones that had to be met in order for the project to receive full funding.
MDA’s translational research program has announced a $250,000 award to ALS Biopharma of Doylestown, Pa., to conduct preclinical studies of a potential treatment for amyotrophic lateral sclerosis (ALS).
The award will enable the biotechnology company to test two different compounds based on heat shock protein 70 (HSP70) in an established mouse model of ALS. After selecting the biologic agent that works best, ALS Biopharma plans to conduct the additional studies required prior to applying to the U.S. Food and Drug Administration (FDA) for permission to move toward human testing.
The MDA award will be disbursed over two years as various milestones are met. “MDA is pleased to be able to support these critical studies for a potential ALS therapy,” said Jane Larkindale, director of MDA's translational research program. “We’re excited to be able to determine if this approach is feasible for ALS."
Heat shock proteins
Heat shock proteins (HSPs) are a class of naturally occurring proteins whose production increases when cells are exposed to heat or other kinds of stress. HSPs can function as “chaperones” for other proteins, helping them fold into the right shape, preventing them from forming abnormal clumps, and blocking cell death.
Several diseases, including Alzheimer disease, Parkinson disease and ALS, are thought to result in part from misfolded and abnormally clumped proteins in cells of the central nervous system. Motor neurons (muscle-controlling nerve cells that are lost in ALS) are considered to be particularly vulnerable to these problems because they cannot mount a typical heat shock response.
About the study
Preliminary studies of HSP70 in the ALS G93A SOD1 mouse model (in which the mice have a mutation in the SOD1 gene, causing an ALS-like disease) have shown that the compound can delay the onset of ALS symptoms and improve survival time. Mice treated with HSP70 showed an eight- to 10-fold improvement in time to symptom onset and death, as compared to mice treated with riluzole (Rilutek), the only drug currently approved by the FDA for the treatment of ALS. These studies were conducted by Carolanne Milligan, a professor of neurobiology and anatomy at Wake Forest University School of Medicine in Winston-Salem, N.C.
For one chemical modification of HSP70, the company will employ FDA-approved approaches that may improve the pharmaceutical properties of the protein. Unmodified HSP70 will be evaluated side by side for comparison purposes.
Meaning for people with ALS
If either version of the HSP70 biologic agent is sufficiently safe and beneficial in mice, ALS Biopharma plans to move as quickly as possible toward testing it in people with ALS.