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(Abst.) Regenerative approach to MS treatment

 
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PostPosted: Fri Oct 11, 2013 5:34 pm    Post subject: (Abst.) Regenerative approach to MS treatment Reply with quote

From PubMed, October 11, 2013:

Quote:
Nature. 2013 Oct 9.

A regenerative approach to the treatment of multiple sclerosis

Deshmukh VA, Tardif V, Lyssiotis CA, Green CC, Kerman B, Kim HJ, Padmanabhan K, Swoboda JG, Ahmad I, Kondo T, Gage FH, Theofilopoulos AN, Lawson BR, Schultz PG, Lairson LL.

Department of Chemistry, The Scripps Research Institute, 10550, North Torrey Pines Road, La Jolla, California 92037, USA.

Progressive phases of multiple sclerosis are associated with inhibited differentiation of the progenitor cell population that generates the mature oligodendrocytes required for remyelination and disease remission.

To identify selective inducers of oligodendrocyte differentiation, we performed an image-based screen for myelin basic protein (MBP) expression using primary rat optic-nerve-derived progenitor cells.

Here we show that among the most effective compounds identifed was benztropine, which significantly decreases clinical severity in the experimental autoimmune encephalomyelitis (EAE) model of relapsing-remitting multiple sclerosis when administered alone or in combination with approved immunosuppressive treatments for multiple sclerosis. Evidence from a cuprizone-induced model of demyelination, in vitro and in vivo T-cell assays and EAE adoptive transfer experiments indicated that the observed efficacy of this drug results directly from an enhancement of remyelination rather than immune suppression.

Pharmacological studies indicate that benztropine functions by a mechanism that involves direct antagonism of M1 and/or M3 muscarinic receptors.

These studies should facilitate the development of effective new therapies for the treatment of multiple sclerosis that complement established immunosuppressive approaches.

PMID: 24107995


The abstract can be seen here.
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PostPosted: Sun Oct 13, 2013 10:51 pm    Post subject: Promising new strategy to treat MS (Medical News Today) Reply with quote

More on this from Medical News Today, October 11, 2013:

Quote:
Promising new strategy to treat multiple sclerosis

Scientists at The Scripps Research Institute (TSRI) have identified a set of compounds that may be used to treat multiple sclerosis (MS) in a new way. Unlike existing MS therapies that suppress the immune system, the compounds boost a population of progenitor cells that can in turn repair MS-damaged nerve fibers.

One of the newly identified compounds, a Parkinson's disease drug called benztropine, was highly effective in treating a standard model of MS in mice, both alone and in combination with existing MS therapies.

"We're excited about these results, and are now considering how to design an initial clinical trial," said Luke L. Lairson, an assistant professor of Chemistry at TSRI and senior author of the study, which is reported online in Nature.

Lairson cautioned that benztropine is a drug with dose-related adverse side effects, and has yet to be proven effective at a safe dose in human MS patients. "People shouldn't start using it off-label for MS," he said.

A New Approach

...

In MS, immune cells known as T cells infiltrate the upper spinal cord and brain, causing inflammation and ultimately the loss of an insulating coating called myelin on some nerve fibers. As nerve fibers lose this myelin coating, they lose their ability to transmit signals efficiently, and in time may begin to degenerate. The resulting symptoms, which commonly occur in a stop-start, "relapsing-remitting" pattern, may include limb weakness, numbness and tingling, fatigue, vision problems, slurred speech, memory difficulties and depression, among other problems.

Current therapies, such as interferon beta, aim to suppress the immune attack that de-myelinates nerve fibers. But they are only partially effective and are apt to have significant adverse side effects.

In the new study, Lairson and his colleagues decided to try a complementary approach, aimed at restoring a population of progenitor cells called oligodendrocytes. These cells normally keep the myelin sheaths of nerve fibers in good repair and in principle could fix these coatings after MS damages them. But oligodendrocyte numbers decline sharply in MS, due to a still-mysterious problem with the stem-like precursor cells that produce them. "Oligodendrocyte precursor cells (OPCs) are present during progressive phases of MS, but for unknown reasons don't mature into functional oligodendrocytes," Lairson said.


The whole article can be seen here.
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