SMA: ISIS-SMNRx To Be Tested in Presymptomatic Infants

The experimental antisense drug will be tested in infants with a genetic spinal muscular atrophy diagnosis who are to date without symptoms
Article Highlights:
  • ISIS-SMNRx is an experimental drug being developed by Biogen Idec and Isis Pharmaceuticals; it's designed to raise levels of the SMN protein, which is deficient in the cells of SMA patients.
  • The new trial will test the drug in infants who have a genetic diagnosis of SMA but do not yet have SMA symptoms, with the goal of preventing development of or reducing these symptoms.
  • MDA-supported laboratory research contributed to the development of ISIS-SMNRx.
by Margaret Wahl on March 16, 2015 - 11:03am

Biogen Idec has announced plans to run a phase 2 clinical study of the experimental drug ISIS-SMNRx  in infants with spinal muscular atrophy (SMA)who are less than 6 weeks old and have a genetic diagnosis of the disorder but are not yet showing symptoms. 

ISIS-SMNRx is being developed by Isis Pharmaceuticals in collaboration with Biogen Idec. Developed using a gene-modifying strategy known as antisense, it targets the SMN2 gene and encourages production of the full-length SMN protein that is needed but deficient in SMA-affected cells. It is hoped that administering this drug very early in life may prevent the development of SMA-associated weakness. MDA-funded laboratory research contributed to the development of ISIS-SMNRx.

ISIS-SMNRx is also being tested in ongoing, open Phase 3  trials in infants with SMA who are up to 7 months old and showing symptoms (ENDEAR), and in children with SMA who are 2-12 years old (CHERISH).

The new phase 2 exploratory clinical study – dubbed NURTURE – is being conducted in presymptomatic infants with a genetic SMA diagnosis  to see whether early treatment with ISIS-SMNRx, before signs of SMA are evident, could delay or even prevent the development of the disease, as well as to further investigate the safety and tolerability of the drug.

In October, Isis announced positive results from phase 2 clinical trials of ISIS-SMNRx in infants and children with SMA

About the ISIS-SMNRx trial in infants without symptoms

All trial participants will receive the drug, which will be administered via a thin needle into the fluid surrounding the spinal cord ("intrathecally") in a procedure commonly referred to as a lumbar puncture. The babies will receive one injection every four months over approximately  2.5 years, for a total of about  10 injections. They'll be required to stay overnight in the hospital on the night of the first injection and to return to the study center the day after each later injection.

Participants will also need to return to the study center periodically during the course of the trial so that their health, safety and development can be monitored. In addition, study team members will contact families on a monthly basis to check on their child's health.

The trial is expected to include up to 25 infants from around the world, with participating sites at centers in the U.S., Taiwan and other countries throughout the world.

It may be possible to take part in this trial by relocating to a country where there is a study site, but legal or regulatory barriers to doing so may exist in some situations. Biogen Idec strongly recommends that families contact the desired study site to discuss their specific circumstances and potential eligibility before making any decisions about relocation.

Participants in the trial of ISIS-SMNRx for presymptomatic infants must:

  • have been born between 37 and 42 weeks of pregnancy  for single births or 34 to 42 weeks of pregnancy for twin births (in other words, have reached an adequate gestational age)
  • have a confirmed genetic diagnosis of SMA, with two or three copies of the survival motor neuron 2 (SMN2) gene present
  • have results on an electrical test of muscle function known as a compound muscle action potential (CMAP) of at least 1 millivolt at baseline
  • meet all enrollment criteria per evaluation by a study doctor
  • enroll and receive the first dose of ISIS-SMNRx within 6 weeks of birth

Participants must not:

  • have any clinical signs or symptoms at screening or immediately prior to dosing with ISIS-SMNRx that are, in the opinion of the study doctor, strongly suggestive of SMA
  • have any clinically significant abnormalities in laboratory tests
  • have low blood oxygen levels ("hypoxemia")
  • have received treatment with any SMA-specific investigational drug, agent or device
  • have received any prior gene therapy, antisense treatment or cell transplantation

Note: This is not a complete list of study criteria.

For more information

For details and contact information for the presymptomatic infant study of ISIS-SMNRX (NURTURE) , see  A Study of Multiple Doses of ISIS-SMNRx Delivered to Infants with Genetically Diagnosed and Presymptomatic SMA, or enter NCT02386553in the search box at For information about the symptomatic infant trial (ENDEAR), see A Study to Assess the Efficacy and Safety of ISIS-SMNRx in Infants With SMA, or enter NCT02193074 in the search box at For information about the trial in children ages 2-12 (CHERISH) , see A Study to Assess the Efficacy and Safety of ISIS-SMNRx in Patients with Later-Onset SMA, or enter NCT02292537 in the search box at

For more about ISIS-SMNRx, see ISIS-SMNRx on the Isis site.

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