ALS Clinical Trials

Antisense Oligonucleotide Therapy for SOD1 Related Familial ALS
What: This study utilizes ISIS-SOD1RX, a novel therapy for SOD1-related ALS that targets and reduces the production of disease-causing proteins. This therapy involves administrating a dose of antisense oligonucleotides, a biochemical similar to DNA, into patients’ cerebrospinal fluid (CSF), the fluid that surrounds and cushions the brain and spinal cord. Dr. Timothy Miller at Washington University in St. Louis, Dr. Don Cleveland at the University of California-San Diego and Dr. Richard Smith at the Center for Neurologic Study, in collaboration with Isis Pharmaceuticals in Carlsbad, California, have demonstrated that these antisense oligonucleotides distribute widely in the brain and spinal cord, decrease their intended target (SOD1), and delay disease in an animal model of ALS. For more information about this study, please read the official press release.

Background: For 90% of patients, ALS is a “sporadic” disease that does not run in their families. However, about 10% of people with ALS have a strong family history of the illness. When ALS runs in families, it is called “familial ALS.” Of those with ALS in their families, about 20% of these families have mutations in the SOD1 protein A genetic test is available to determine if an individual carries the SOD1 mutation. This specialized test can be requested by any physician. We do not yet understand how exactly SOD1 causes ALS.

Inclusion Criteria:
Participants must:
1. have clinical signs of weakness associated with ALS.
2. have familial ALS with a documented SOD-1 gene mutation.
3. be 18 years or older.
4. have a vital capacity (VC) of 50% of predicted or higher.
5. if taking Riluzole, be on a stable dose for at least 30 days before infusion of study medication

Exclusion Criteria:
Participants must not:
1. be undergoing treatment with another investigational agent within 1 month of screening.
2. have any condition that may impact intrathecal infusion.
3. have any unstable medical condition such as cardiac, pulmonary, renal, hepatic, or active infectious disease.

Study Details: Each participant will be in the study for approximately 50 days, which includes four visits to the site facility and phone assessments. After the initial screening to determine eligibility, participants will be admitted to a research unit for approximately 48 hours. During this time, an intrathecal catheter (a tube inserted into the space surrounding the spinal cord) will be placed and the participant will undergo a 12 hour infusion of study medication. Safety, tolerability, and pharmacokinetic measures will be performed at regular intervals and at follow-up visits to determine the safety and tolerability of the drug.

Target number of participants: 32

Opening Dates: Closed to enrollment

Participating Centers and Principal Investigators:

  • Washington University in St. Louis (St. Louis, Missouri), Alan Pestronk, MD.
  • Massachusetts General Hospital (Boston, Massachusetts), William David, MD.
  • Johns Hopkins University (Baltimore, Maryland), Jeffrey Rothstein, MD, PhD.
  • Methodist Neurological Institute (Houston, Texas), Ericka Simpson, MD.

Who to contact: If you have questions or would like to enroll in the study, please contact Jennifer Jockel-Balsarotti, Clinical Research Specialist at Washington University in St. Louis, at (314) 362-8624 or