LIBERTYVILLE, Ill. & CARLSBAD, Calif. & WOODRIDGE, Ill.–Families of Spinal Muscular Atrophy (FSMA, www.curesma.org), Invitrogen Corporation (NASDAQ:IVGN)(www.invitrogen.com), and deCODE chemistry & biostructures (www.decodechembio.com) announced today they have identified a protein that is a potential molecular target for the treatment of Spinal Muscular Atrophy (SMA). In its most severe form, SMA often leads to death in infancy, and there is currently no treatment or cure. Research published today in the journal ACS Chemical Biology of the American Chemical Society, entitled “DcpS as a Therapeutic Target for Spinal Muscular Atrophy,” details the identification and characterization of a protein that offers a novel biological mechanism for designing new SMA therapeutics.

SMA is an inherited genetic disorder that affects approximately one in every 6,000 births in the US. The molecular basis of the disease is a deficiency in production of a specific protein – Survival Motor Neuron (SMN) protein. Motor neuron function is acutely sensitive to lowered SMN protein levels. This cellular defect is the underlying basis for the loss of control of muscles in the limbs, neck and chest in these patients. Because the genetic capability to produce SMN protein is not completely eliminated in SMA patients due to the unique presence of a back-up gene, drugs that increase SMN protein levels in motor neurons are expected to modulate the severity of the disease and have done so in SMA mouse models.

Previously, researchers at deCODE chemistry & biostructures, with funding from Families of SMA, had developed a class of compounds called C-5 substituted quinazolines, which increased expression of SMN protein, potentially giving clinical investigators a new class of compounds to utilize for the treatment of SMA. However, the mechanism behind this increase in SMN production was unknown.

“While the identification of compounds that increase SMN expression represents significant hope to patients with SMA, we still did not understand the mode of action of these compounds in SMA,” noted Jill Jarecki, Ph.D., Research Director at Families of SMA. “The results outlined in the paper represent a new understanding of the physiological mechanisms that can increase SMN expression and will allow us to move forward in advancing potential treatments for SMA. This discovery gets to the level of really understanding how SMN deficiency can be corrected in the cells of the body, which in turn will open up many new ways of developing therapies.”

In the present study, researchers used a lead compound from the FSMA funded program, to probe Invitrogen’s high-density ProtoArray™ protein microarray for candidate proteins binding to the test compounds. The ProtoArray allowed researchers to rapidly identify a specific human protein called DcpS (human mRNA decapping scavenger enzyme) that interacted with the FSMA compounds. Additional functional experiments preformed by the laboratory of Dr. Megerditch Kiledjian at Rutgers, The State University of New Jersey confirmed that DcpS activity is modulated by the FSMA compounds.

“The identification of DcpS as a novel drug target for SMA is but one example of how Invitrogen technologies bring unique value to basic and applied research,” said Brian Pollok, Ph.D., Chief Scientific Officer for Invitrogen. “In 2006, we started working with FSMA to define the biomolecular mechanism for how these compounds up-regulate SMN production, and the successful outcome of this collaboration is very gratifying. Invitrogen is committed to creating advanced technologies which progress the understanding of disease biology and support the development of new therapies.”

“We have long been involved in working with FSMA to try and find a cure for this disease,” said Mark Gurney, Ph.D. Sr. Vice President of Drug Discovery and Development at deCODE, and the paper’s corresponding author. “The work carried out by ourselves in collaboration with Invitrogen, Rugters, and FSMA helps science understand the mechanisms of SMA, and demonstrates the value of protein structures in translational research. While still in the discovery phase of drug development, the FSMA compounds represent novel potential treatments for SMA. We look forward to continuing our work with FSMA to move the drug candidate forward so that patients may benefit from a potential new medicine to combat SMA.”