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Oct 31, 2013
 |  BC Innovations  |  Targets & Mechanisms

Benztropine for MS

Although the secondary progressive multiple sclerosis space is filling up with new compounds, few have shown the ability to remyelinate neurons. A new study suggests that an ancient Parkinson's disease drug-benztropine-could accomplish that task in secondary progressive multiple sclerosis, although it might require reformulation to improve activity and specificity.1

There are multiple immunomodulatory therapies on the market that stop or slow the autoimmune attack on neurons by myelin-specific

T cells in relapsing-remitting MS (RRMS). Nevertheless, within 20 years of diagnosis, the vast majority of patients will progress to secondary progressive MS (SPMS). At that point, available immunomodulatory agents are no longer able to prevent further neuronal degeneration.

The only drug on the market for SPMS is mitoxantrone, a generic chemotherapeutic that carries a boxed warning about potential cardiotoxicity.

The SPMS pipeline includes seven compounds in clinical development. A few compounds, including the antibodies BIIB033 and HIgM22, potentially can remyelinate axons and thus reverse the course of the disease.

BIIB033, from Biogen Idec Inc., targets leucine-rich repeat neuronal protein 1 (LINGO-1) and is in Phase II testing. HIgM22, a remyelinating antibody from Acorda Therapeutics Inc., is in Phase I testing.

Now, a group of researchers from The Scripps Research Institute and the California Institute for Biomedical Research (Calibr) have developed a screen for small molecules that can accomplish remyelination.

Specifically, the screen identifies compounds that promote the differentiation of oligodendrocyte precursor cells (OPCs) into myelin-promoting mature oligodendrocytes. In MS, the differentiation process is impaired.2,3

The team was led by Peter Schultz, a professor of chemistry at Scripps and founding director of Calibr; Luke Lairson, an assistant professor at Scripps and a principal investigator at Calibr; and Brian Lawson, an assistant professor of immunology at Scripps. The team also included researchers from the Salk Institute for Biological Sciences and Hokkaido University.

The group screened about 100,000 small molecules in rat OPCs using an imaging assay that detects expression of myelin basic protein (MBP). MBP expression indicates that...

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