Use of Therapeutic Antibodies as a Novel Treatment for Multiple Sclerosis

Multiple sclerosis (MS) is a disease of the central nervous system in which the immune system attacks the brain and spinal cord, typically resulting in muscle weakness, problems with vision and coordination, pain, and in some patients, cognitive impairments. The disorder affects approximately 400,000 people in the U.S. and more than 2.5 million people worldwide. Patients with relapsing forms of MS are currently treated with one of three FDA-approved interferon beta agents or with glatiramer acetate. Unfortunately, each of these treatments is not effective in a substantial number of patients. Therefore, there is an urgent need to develop new and more effective treatments for MS, especially for those MS patients that fail to respond or respond only partially to standard immunotherapy. 

Drs. Bielekova, Martin, and McFarland of the National Institute of Neurological Disorders and Stroke (NINDS) of the NIH discovered that daclizumab, a humanized antibody to the interleukin-2 receptor alpha chain (IL2Rα) is effective in treating MS. Daclizumab was first developed in the lab of Dr. Waldmann and approved in the U.S. for preventing organ transplant rejection. The NIH investigators led a small clinical trial of patients with MS who did not respond to interferon-beta alone and found that adding daclizumab improved patient outcome. Patients who received the combined therapy had a 78 percent reduction in new brain lesions and a 70 percent reduction in total lesions, along with other significant clinical improvements. Daclizumab was also very well tolerated. Based on this trial the NIH investigators anticipated that daclizumab and other antiIL-2Rα antibodies would be useful either as combination therapy or stand-alone treatment in MS and patent applications disclosing these findings were filed by the NIH. 

The technology is exclusively licensed to Abbott (formerly Facet Biotech/PDL) who in collaboration with Biogen Idec has initiated and is currently enrolling patients for a Phase III study with a subcutaneous formulation of daclizumab intended for monthly administration. The licensee has recently concluded a study that enrolled 230 patients with MS which confirmed that using daclizumab as an add-on therapy helped patients whose symptoms had relapsed while they were taking interferon-beta. Dr. Bielekova has led several small scale clinical trials at the NIH that have lead to the conclusion that daclizumab monotherapy is effective in most patients who experienced persistent MS disease activity with interferon-beta therapy. While Drs. Bielekova, Martin, McFarland and Waldmann helped the transfer of this technology from bench to bedside by conducting clinical trials and disseminating the results of their findings, the technology transfer professionals at the NIH helped transfer this valuable technology to biopharmaceutical companies to ensure that FDA approved therapies are developed that can further help in treating MS worldwide. 

Awardees

NIH - National Institute of Neurological Disorders and Stroke

• Dr. Bibiana Bielekova 
• Dr. Roland Martin 
• Dr. Henry McFarland 

NIH - National Cancer Institute 

• Dr. Thomas Waldmann
• Dr. Melissa Maderia
• Dr. Martha Lubet
• Dr. Charlotte McGuinness
• Thomas Close

NIH - Office of Technology Transfer 

• Dr. Surekha Vathyam 
• Mojdeh Bahar 
• Richard Rodriguez