The nonprofit advocacy group Cure SMA has awarded Christine DiDonato a $140,000 grant to study how specific proteins reduce force production and endurance in muscles affected by spinal muscular atrophy (SMA).
SMA is a childhood disease that occurs in one of 10,000 births. It is characterized by degeneration of the motor neurons in the spinal cord, which causes limb and trunk muscle weakness that progresses to paralysis and ultimately death. The disease is caused by mutations of the survival motor neuron 1 or SMN1 gene.
With the new grant, DiDonato, associate professor of pediatrics at the Ann & Robert H. Lurie Children’s Hospital and Northwestern University, will examine how proteins in SMA skeletal muscle are wrongly regulated.
In their experiments, DiDonato and her team will use normal versions of these misregulated proteins in a mouse model of SMA to determine their effect on the ability of SMA muscle to contract properly. Her studies could potentially help researchers better understand how misregulation of proteins reduce force production and endurance in SMA muscle.
This work has important parallels to CK-2127107 (tirasemtiv), an investigational drug candidate that aims to improve patients’ skeletal muscle function and reduce muscle fatigue. The complex consists of three proteins integral to muscle contraction. Cytokinetics is jointly developing this skeletal muscle activator drug with Astellas Pharma as a treatment for SMA and other conditions characterized by neuromuscular or non-neuromuscular dysfunction, muscular weakness or muscle fatigue.
These drugs may eventually be used alone or in combination with SMN-inducing drugs to give SMA patients enhanced functional benefits.
“Many therapeutics increase SMN levels at a time when patients have already lost a significant portion of their motor neurons. This creates a situation where there is enhancement of motor neuron function in the presence of decreased motor neuron input to muscle,” DiDonato said in a news release. “We believe greater therapeutic benefit could be achieved by targeting the muscle as well. In this study, we will learn about protein misregulation in SMA muscle. This will give us important insight into future therapeutic development targeting muscle.|