Trial of Antisense Drug Opens for Children with SMA

Isis Pharmaceuticals has launched a trial to test multiple doses of its experimental antisense drug ISIS-SMNRx in 24 children with SMA at four US centers

Article Highlights:
  • Antisense-based therapies block specific sections of genetic instructions, changing the way a cell constructs a protein.
  • In spinal muscular atrophy, the goal of antisense therapy is to change the way instructions from the SMN2 gene are interpreted so that full-length, functional SMN protein can be made.
  • The new phase 1b/2a trial of the experimental drug ISIS-SMNRx will assess safety, tolerability and the effects the body has on the drug (pharmacokinetics).
  • Investigators hope to enroll a total of 24 children with SMA at sites around the country. ISIS-SMNRx was developed by Isis Pharmaceuticals in collaboration with MDA-supported researcher Adrian Krainer at Cold Spring Harbor Laboratory.
by Amy Madsen on November 15, 2012 - 2:45pm

Update (Nov. 22, 2013): In a Nov. 22, 2013, press release, Isis Pharmaceuticals announced it would investigate a higher dose of ISIS-SMNRx in children with SMA than originally planned. It will add a 12-milligram cohort to the ongoing phase 1b/2a study.

Update (Sept. 5, 2013): This phase 1 trial of multiple doses of ISIS-SMNRx in children with SMA is ongoing but is no longer recruiting participants. The phase 1, single-dose study of this drug in children with SMA has been completed.

A phase 1b/2a trial to test the safety and tolerability of multiple doses of the experimental drug ISIS-SMNRx in children with spinal muscular atrophy (SMA) is now open at sites in New York and Salt Lake City, with additional sites expected to open in Boston and Dallas.

Investigators hope to enroll a total of 24 children with SMA ages 2 to 15 in the trial.

ISIS-SMNRx, 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.

Isis announced the opening of the new trial Nov. 1, 2012. MDA research grantee Adrian Krainer at Cold Spring Harbor (N.Y.) Laboratory has been working with Isis to develop ISIS-SMNRx.

Full-length functional protein is the goal

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.

SMN1 genes are flawed or missing in children and adults with SMA. Although people with SMA have "backup" SMN2 genes, the protein made from them is a shorter, relatively nonfunctional molecule compared to the protein made from SMN1 genes.

Antisense-based therapeutic strategies, which change the way SMN2 genetic instructions are "spliced," have shown promise in mouse models of SMA.

Trial will analyze multiple doses of ISIS-SMNRx

The newly opened trial of ISIS-SMNRx is slated to include 24 children with genetically confirmed SMA who:

  • are 2 to 15 years old;
  • show clinical signs of SMA;
  • are able to complete all study procedures, measurements and visits;
  • meet the site-study institution criteria for use of anesthesia or sedation; and
  • meet other study criteria.

Each participant will receive either two or three doses of the drug into the fluid around the spinal cord (intrathecally) and then will be followed for the duration of the study, which is expected to last 36 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 (pharmacokinetics).

Data from the study is expected to help inform later-stage trials.

In a completed phase 1 study in children with SMA, all trial participants received a single dose of ISIS-SMNRx, administered directly into the cerebral spinal fluid. The drug was found to be safe and well-tolerated.

Development of ISIS-SMNRx

Isis currently is in collaboration with multinational biotechnology company Biogen Idec, headquartered in Weston, Mass., to develop and potentially commercialize the investigational compound ISIS-SMNRx to treat all types of SMA that result from a deficiency of SMN protein.

The U.S. Food and Drug Administration has granted fast-track designation and orphan drug status to ISIS-SMNRx for the treatment of people with SMA. A fast track designation allows for faster review of drugs that treat serious diseases and fill an unmet need, while orphan drug status provides economic incentives to companies developing treatments for rare diseases.

Trial site information

Boston Children's Hospital
(not yet recruiting)
Boston, Massachusetts, United States, 02115
Principal Investigator: Basil Darras, M.D.
Contact: Rebecca Parad (617-355-2752)
Contact: Elizabeth Shriber (617-218-4677)

Columbia University Medical Center
New York, New York, United States, 10032
Principal Investigator: Claudia Chiriboga, M.D.
Contact: Nicole Holuba LaMarca, MSN, CPNP (212-304-5205)

UT Southwestern Medical Center — Children's Medical Center Dallas
(not yet recruiting)
Dallas, Texas, United States, 75207
Principal Investigator: Susan Iannaccone, M.D.
Contact: Susan Iannaccone, M.D. (214-456-5220)
Contact: Shanda Johnson (214-456-5501)

University of Utah School of Medicine
Salt Lake City, Utah, United States, 84132
Principal Investigator: Kathryn Swoboda, M.D.
Contact: Nicole Rausch, CCRC (801-585-9055)

For additional details, see An Open-Label Safety, Tolerability and Dose-Range Finding Study of Multiple Doses of ISIS SMNRx in Patients With Spinal Muscular Atrophy (SMNRx-CS2), or enter NCT01703988 into the search box at

More about antisense strategy in SMA

To learn more about this subject, read:

  • 'Antisense' Ameliorates SMA Symptoms in Mice — mice with a severe SMA-like disease that were injected with a synthetic "antisense" molecule developed bigger, more structurally sound muscles than untreated mice (Quest News Online, March 15, 2011)


About Clinical Trials

About Clinical Trials

A clinical trial is a test, in humans, of an experimental treatment. Although it's possible that benefit may be derived from participating in a clinical trial, it's also possible that no benefit, or even harm, may occur.

MDA has no ability to influence who is chosen to participate in a clinical trial.

To learn more, see Learn About Clinical Studies and Being a Co-Adventurer, which is about neuromuscular disease clinical trials. To see a continuously updated database of clinical trials, go to

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