SMA Research: Back to the Beginning

SMA cell 'reprogramming' may significantly aid search for effective drugs

by Quest Staff on January 28, 2009 - 2:01pm

In a development that could lead to better screening of drugs for spinal muscular atrophy (SMA), skin cells from a child with SMA1 have been "reprogrammed" back to a stemlike state and then coaxed to develop into SMA-affected motor neurons, the nerve cells that normally control muscle movement but malfunction and die in this disease.

Allison Ebert, assistant scientist in the laboratory of Clive Svendsen at the University of Wisconsin-Madison, and colleagues, who published their findings online Dec. 21 in the journal Nature, say the results will allow the study of SMA in motor neurons in the lab and probably will allow drugs for SMA to be screened more effectively than is currently possible.

Although they note that further testing is necessary, so far they believe the child's SMA-affected cells faithfully reproduce the SMA disease process and haven't been altered by the reprogramming procedure – a critical feature for accurate research.

The investigators also took skin cells from the child's unaffected mother and treated them the same way as the child's cells. In contrast to the child's cells, the mother's unaffected motor neurons are developing normally, they say.

Christian Lorson
Christian Lorson, who receives MDA funding for his work in SMA, was part of a team that successfully turned skin cells into SMA-affected nerve cells – an important element for accurate testing of SMA treatments.

The research team included Christian Lorson, associate professor at the University of Missouri-Columbia, who has MDA funding for SMA work. Lorson, with graduate students Virgina Mattis and Frankie Rose, analyzed cellular levels of the SMN protein, a deficiency of which is the root cause of SMA.

Although motor neurons have been created from the skin cells of patients with other neurologic diseases, including amyotrophic lateral sclerosis (ALS) (see Research Roundup, ALS Newsmagazine, October 2008), those reprogrammed motor neurons so far have not demonstrated disease-specific effects, the researchers note.

The SMA-affected motor neurons in the current study have also responded positively to compounds known to increase SMN protein levels. Raising SMN levels to save motor neurons is a major goal of current SMA drug development.

The researchers note that "this new model should provide a unique platform for studies aimed at both understanding SMA disease mechanisms that lead to motor neuron dysfunction and death, and the potential discovery of new compounds to treat this devastating disorder."

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