ALS Research: Restoring Disrupted Connections

A chemical called microRNA 206 appears to help re-establish nerve-muscle connections after injury in ALS research mice.

by Margaret Wahl on December 16, 2009 - 6:35pm

A molecule called microRNA 206, produced by muscle fibers after an injury to nerve cells, helps rebuild crucial nerve-muscle communications, say scientists at the University of Texas Southwestern Medical Center in Dallas and Harvard University. They say raising levels of microRNA 206 or amplifying its effects in some other way could become a new therapeutic avenue in amyotrophic lateral sclerosis (ALS).

They found that mice with an ALS-like disease fared worse without microRNA 206 than with it.

Increasing evidence suggests that the problem in ALS may not be confined to the nerve cells themselves, but to the connections between nerve fibers (which sprout from the cell bodies) and muscle fibers (the neuromuscular junctions), cells of the immune system, and other types of cells.

About the new findings

MicroRNAs are small strands of RNA (ribonucleic acid) that interfere with gene activity. Unlike most RNA, which is used by cells as an instruction book to make proteins, microRNA molecules stick to pieces of RNA that the cell would otherwise use to make protein molecules and interfere with that activity.

MicroRNAs regulate many kinds of cellular activity.

Eric Olson at the University of Texas Southwestern Medical Center in Dallas, with colleagues there and at Harvard University, reported the new findings in the Dec. 11, 2009, issue of the journal Science.

When the scientists genetically engineered mice to develop an ALS-like disease and also to lack microRNA 206, they found the mice had faster disease progression and died earlier than mice with the same disease that had normal microRNA 206.

Mice with and without microRNA 206 developed their first disease symptoms at about the same time, however.

That and other experimental results led the investigators to the conclusion that microRNA 206, which comes from muscle fibers, acts in response to injury to nerve tissue and becomes important only after such injury occurs.

MicroRNA 206 appears to help compensate for nerve injury, albeit incompletely, at least in ALS.

Meaning for people with ALS

While there are no immediate implications for people with ALS, investigators Eric Olson and Andrew Williams, both at UT Southwestern, have filed patent applications related to this work, indicating they may believe it has potential for drug development.

In addition to his academic position, Olson is a co-founder of and chief scientific adviser to miRagen Therapeutics, a Boulder, Colo., biotechnology company that develops microRNA-based therapeutics for cardiovascular and muscle diseases.

MDA's role

MDA did not fund this particular study. However, three of the investigators have received MDA funding for related work.

Eric Olson is a former MDA grantee sudying muscle development and regulation. Jeffrey Elliott, also at the University of Texas Southwestern Medical Center, has current MDA funding to study animal models of ALS and has received earlier ALS-related MDA support. Joshua Sanes at Harvard has received MDA support to study nerve-muscle junctions.

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