On The Track of a Cure for Infants’ Spinal Disease

2/2/2009 12:00:00 AM

Collaborative research involving Rutgers scientist Mike Kiledjian may lead to a drug treatment for spinal muscular atrophy (SMA).

Collaborative research involving Rutgers scientist Mike Kiledjian may lead to a drug treatment for spinal muscular atrophy (SMA), the leading cause of hereditary infant death in the United States.

SMA interferes with development of motor neurons, resulting in muscle weakness and possible death. It occurs once in 6,000 births.

In SMA-affected infants, a faulty gene stops production of an essential protein known as SMN. The protein normally promotes motor neuron survival. However, the body has another genetic system that typically acts as a backup, producing small quantities of normal protein.

While this backup system itself often cannot produce enough protein for long-term survival, its production can be increased twofold with the introduction of a compound known as C5-quinazoline. The latest research by Kiledjian and his colleagues focuses on this synthetic alkaloid compound. It is related to quinine – generally known as a treatment for malaria.

The inadequacy of the backup system can be traced to the action of a scavenger enzyme known as DcpS – one of many proteins normally regulating the SMN protein production. DcpS was first identified by the Kiledjian lab at Rutgers in 2002. Scavenger enzymes such as this roam the body, seeking out and disposing of molecular byproducts. In this case, it also keeps production of the backup system low.

The Families of SMA (an international support group and resource center) had previously reported that C5-quinazoline compounds appear to help the body use its backup system to produce motor neurons. Now the process by which it does this is clear – C5-quinazoline binds to DcpS and inhibits its action, thereby allowing increased protein production. The increase is not expected to yield enough to wipe out all the symptoms of SMA, but it is expected to help ameliorate the situation and it is a step in the right direction. These research findings recently appeared in ACS Chemical Biology, a journal of the American Chemical Society.

Kiledjian, a professor in the Department of Cell Biology and Neuroscience, is conducting his research in collaboration with scientists from Families of SMA, deCODE ChemBio and Invitrogen Corp.

"The results outlined in the paper and carried out in collaboration with Families of SMA, deCode, Invitrogen and Rutgers represent new understanding and will allow us to move forward in advancing potential treatments for SMA," said Jill Jarecki, research director at Families of SMA.

Contact: Joseph Blumberg
732-932-7084 ext. 652
E-mail:blumberg@ur.rutgers.edu