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New Target for Treatment of Multiple Sclerosis?


A study published  in the October, 2014 issue of Nature Medicine points to a new target for the treatment of multiple sclerosis (M.S.).  Inhibiting this target, in a mouse model of the disease, was shown to inhibit the disease in its most advanced stages.

The landmark paper, “B4GALT6 regulates astrocyte activation during CNS inflammation,” was authored by Lior Mayo, Francisco J. Quinta et al. at Harvard Medical School. Abdolmohamad Rostami, M.D. Ph.D., professor and chair of the department of neurology at Thomas Jefferson University, together with Assistant Professor of Neurology Bogoljub Ciric, Ph.D., authored  a commentary article, Astrocyte-derived lactosylceramide implicated in multiple sclerosis,” about the research for Nature Medicine.

“These findings provide a basis for targeting astrocytes, in particular LacCer signaling, as an alternative to most existing M.S. therapies, which modulate the immune system,” said Dr. Rostami.

Patients and researchers have been frustrated by the limited effectiveness of available therapies for M.S., especially for “progressive” M.S., a devastating form of the disease that continues to progress with no interruption.

As Rostami and Ciric write in their commentary, the researchers started by investigating a puzzle in M.S. biology. M.S. is thought of as a disease in which the immune cells attack the neuron’s “insulating” tissue, myelin, which helps speed the signals passing from one cell to the next. A type of brain cell, called an astrocyte, appears to play two roles in the disease – protecting and re-myleninating cells early on, and then later, it appears to participate in the inflammatory reaction that fuels the disease.

Exploring this question, the researchers found that the gene B4GALT6 encodes an enzyme that makes LaCer (latosylceramide) — a lipid-signaling molecule. Increasing LaCer production worsens the disease, while inhibiting LaCer halts progression in a mouse model of late-stage disease, suggesting that this enzyme could be a potent target for developing a novel class of therapies against M.S.

Rostami and Ciric write that LaCer appears to contribute to disease progression by activating astrocytes, which in turn activate inflammatory signals that damage nerve cells; it also contributes to the repression of genes associated with remyelinization.

Drs. Rostami and Ciric were particularly impressed with the studies that bridged the finding to human disease. The Harvard team also showed that in samples taken from humans with M.S., B4GALT6 expression levels were increased, as were markers of astrocyte activation, suggesting that a similar pathway may be at play in humans.

For more information, contact Kate Krauss, 215-955-5507,