Post date: Jun 4, 2013 3:26:38 AM

May 7, 2013

Isis Pharmaceuticals has launched a phase 2 trial to test its experimental antisense drug ISIS-SMNRx in infants with spinal muscular atrophy

A phase 2 clinical trial to test multiple doses of the experimental drug ISIS-SMNRx in infants with spinal muscular atrophy (SMA)has opened at four trial sites in the United States and Canada. Enrollment is expected to begin soon.

ISIS-SMNRx, developed by Isis Pharmaceuticals in Carlsbad, Calif., with Adrian Krainer at Cold Spring Harbor (N.Y.) Laboratory, is based on antisense technology. Antisense molecules are used to block segments of genetic instructions that create proteins, thereby changing the way these instructions are "read" by cells.

The study, which is expected to enroll eight infants with SMA, is designed to enable investigators to determine the optimal dose for a larger planned phase 2-3 study in infants, and also to provide safety and tolerability data on the experimental drug.

Kathie Bishop, executive director of clinical development at Isis, announced the opening of the trial April 23, 2012, at MDA's Scientific Conference in Washington, D.C.

Goal is to produce full-length SMN protein

In the most common form of SMA, genetic mutations in the SMN1 gene lead to a deficiency of SMN ("survival of motor neuron") protein. (Motor neurons are the muscle-controlling nerve cells that are lost in SMA.)

Children and adults with SMA carry one or more copies of a gene called SMN2, which is similar in makeup to SMN1. Usually, SMN protein made from the genetic instructions carried by the SMN2 gene is shorter, relatively nonfunctional and unstable compared to the protein made from SMN1 genes. Sometimes however, natural variations in the cellular protein-building process cause a different "readout" of the SMN2 genetic instructions; the result when this happens is production of full-length, functional SMN protein.

Antisense therapy aims to change the way cells process genetic instructions carried by SMN2, so that the result is always full-length SMN.

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