Researchers discover target that could ease spinal muscular atrophy symptoms

[Guest guest]

Researchers discover target that could ease spinal muscular atrophy

symptoms

http://www.eurekalert.org/pub_releases/2009-01/uom-rdt010709.php

There is no cure for spinal muscular atrophy (SMA), a genetic

disorder that causes the weakening of muscles and is the leading

genetic cause of infant death, but University of Missouri researchers

have discovered a new therapeutic target that improves deteriorating

skeletal muscle tissue caused by SMA. The new therapy enhanced muscle

strength, improved gross motor skills and increased the lifespan in a

SMA model.

" This therapy does not directly target the disease-causing gene;

instead it targets the pathways that affect muscle maintenance and

growth, " said Lorson, investigator in the S. Bond

Life Sciences Center and associate professor of veterinary

pathobiology in the MU College of Veterinary Medicine. " We

administered a particular protein, follistatin, to SMA mouse models

to determine if enhanced muscle mass impacts the symptoms of SMA.

After treatment, the mice had increased muscle mass, gross motor

function improvement and an increase in average life span of 30

percent. "

With the therapy, MU researchers inhibited myostatin, a protein that

limits muscle tissue growth. Myostatin activity can be reduced

significantly by enabling several proteins that bind to myostatin,

including follistatin. When myostatin is inhibited, muscle mass and

strength increase.

SMA is caused by the loss of survival motor neuron-1(SMN1). Humans

have a nearly identical copy gene called SMN2. Because of a single

molecular difference, SMN2 alone cannot compensate for the loss of

SMN1.

" While most work in the SMA field has logically focused on targeting

the SMN2 gene, the results of this study suggest that skeletal muscle

is a viable therapeutic target that may reduce the severity of some

SMA symptoms, " said Lorson, who also is the scientific director for

FightSMA, a private spinal muscular atrophy research foundation in

Richmond, Va. " Because follistatin does not alter the expression

level of SMN protein, the most effective treatment would combine

strategies that directly address the genetic defect in SMA as well as

SMN-independent strategies that enhance skeletal muscle. "

###

The study, " Delivery of recombinant follistatin lessens disease

severity in a mouse model of Spinal Muscular Atrophy, " was published

online in the December issue of Human Molecular Genetics. The

research team also consisted of graduate students ie Rose and

Virginia Mattis, and Hans Rindt, an assistant research professor.

Recently, Lorson was awarded a $370,000 grant from the Muscular

Dystrophy Association to continue his research on the role of muscle

in SMA.