A 24-person, phase 1 trial to test the safety and tolerability of the experimental drug ISIS-SMNRx in children with spinal muscular atrophy (SMA) is now open at Columbia University Medical Center in New York, with additional sites expected to open in Boston, Philadelphia, Dallas and Salt Lake City.
The drug, developed by Isis Pharmaceuticals in Carlsbad, Calif., is based on antisense technology, a therapeutic strategy that involves blocking parts of genetic instructions for proteins, thereby changing the way these instructions are "read" by cells.
In SMA, the goal is to change the way cells process the genetic instructions for the SMN protein, so that more of the fully functional, full-length form of the protein can be made from a gene called SMN2.
Children and adults with SMA have SMN2 genes, but the protein made from them is a shorter, relatively nonfunctional molecule compared to the protein made from SMN1 genes. SMN1 genes are flawed or missing in people with SMA.
Antisense-based therapeutic strategies, which change the way SMN2 genetic instructions are "spliced," have shown promise in mouse models of SMA.
MDA research grantee Adrian Krainer at Cold Spring Harbor (N.Y.) Laboratory has been working with Isis to develop ISIS-SMNRx.
The newly opened trial of ISIS-SMNRx is slated to include 24 children with SMA who are 2-14 years old; have clinical signs of SMA and genetic test results showing absence of SMN1 genes; do not have a feeding tube; and meet respiratory and other study criteria.
Each participant will receive a single injection of one of four dosage levels of the drug into the fluid around the spinal cord (intrathecally) and then will be followed for four weeks. The investigators will look for adverse events (an indication of safety and tolerability), and will analyze how the drug is absorbed, distributed, metabolized and excreted by the body.
For details and contact information, see An Open-Label Safety, Tolerability and Dose-Range Finding Study of ISIS SMNRx in Patients With Spinal Muscular Atrophy, or enter NCT01494701 into the search box at Clinicaltrials.gov.
For more about antisense strategies for SMA, see:
Editor's note 1/4/12: On Jan. 4, 2012, Isis and biotechnology company Biogen Idec announced their collaboration for development of ISIS-SMNRx.
For details, see