SMA: Trial Tests Antisense Therapy in Infants

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

Kathie Bishop, executive director of clinical development at Isis, announced the opening of a new phase 2 trial to test ISIS-SMNRx in infants with SMA April 23, 2012, at MDA's Scientific Conference in Washington, D.C.
Article Highlights:
  • In spinal muscular atrophy (SMA), the goal of antisense therapy is to change the way genetic instructions are interpreted so that full-length SMN protein can be made.
  • The experimental drug ISIS-SMNRx was developed by Isis Pharmaceuticals, in collaboration with MDA-supported Adrian Krainer at Cold Spring Harbor Laboratory.
  • The new phase 2 trial will test the safety, tolerability and pharmacokinetics (the way the body affects a drug) of multiple doses of ISIS-SMNRx in infants with SMA.
by Amy Madsen on May 7, 2013 - 12:15pm


Update (Jan. 14, 2014): Contact information for Isis Pharmaceuticals has been changed.

Update (Nov. 4, 2013): All centers are now recruiting participants.

Update (Oct. 7, 2013): In an Oct. 3, 2013, press release, ISIS Pharmaceuticals announced that it has administered ISIS-SMNRx to the first infant in the 12-milligram dose group in this study. Isis received a $2 million “milestone” payment from Biogen Idec associated with advancement of the study.

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.

ISIS-SMNRx is compiling a favorable safety record

Each trial participant will receive multiple doses of ISIS-SMNRx, administered intrathecally three times over the duration of the trial. Investigators will assess safety, tolerability and pharmacokinetics.

In a completed phase 1 study in children with SMA ages 2 years to 14 years, ISIS-SMNRx was well-tolerated at all dose levels, with no safety or tolerability concerns. The injection method also was well-tolerated, and measurements of the drug in cerebral spinal fluid and blood showed that it reached expected levels.

ISIS-SMNRx currently is being tested in a study that is designed to examine the safety and tolerability of multiple doses of the drug given over a longer time period. This study is being conducted in children with SMA ages 2 years to 15 years, and is expected to be completed in 2013. Following that, Isis plans to conduct larger phase 3 studies, beginning in early 2014.

To participate in the phase 2 trial for infants

To participate in the trial, infants must be between the ages of 3 weeks and 7 months. In addition, they must:

  • have genetically confirmed chromosome-5-related SMA;
  • live in close proximity to a study site;
  • pass screening evaluations; and
  • meet other criteria.

Study site locations are:

Stanford University Medical Center — recruiting
Stanford, California, United States, 94305
Contact: Shirley Paulose, M.B.B.S., M.S.; 650-724-3792;
Principal investigator: John Day, M.D.

Nemours Children's Hospital — recruiting
Orlando, Florida, United States, 32827
Contact: Dawn Cook, R.N., M.S.N., C.C.R.C.; 407-650-7156;
Principal investigator: Richard Finkel, M.D.

New York
Columbia University Medical Center — recruiting
New York, New York, United States, 10032
Contact: Rosangel Cruz, M.A., B.S.; 212-305-1336;
Contact: Jonathan Marra, M.A.; 212-305-2461;
Principal investigator: Claudia Chiriboga, M.D.

Ontario, Canada
The Hospital for Sick Children (Sick Kids) — recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Lynn MacMillan, R.N.; 416-813-7355;
Principal investigator: Jiri Vajsar, M.D.

For more information

To learn more about the phase 2 trial and ISIS-SMNRx, read:

For additional questions, contact Kristina Lemonidis, Director of Communications and Advocacy Relations at Isis Pharmaceuticals, in Carlsbad, Calif., at (760) 603-2490 or

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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