In a collaboration between the Mayo Clinic and Acorda Therapeutics, Inc., a “first-in-human” trial of the drug rHIgM22 to repair nerve damage caused by multiple sclerosis (MS) is currently recruiting volunteers.
Earlier animal studies of rHIgM22 showed improvements in motor activity, meaning a possible reversal of disability. If successful, this could be a groundbreaking achievement, particularly for those with progressive forms of MS, for which there are no treatments currently available.
How the Drug Works
In MS, the immune system targets myelin, the fatty covering that insulates nerve cells in the brain and spinal cord, and destroys it. The body’s imperfect attempt to repair the damage leaves scar tissue, or “plaques,” in place of myelin. These plaques are less effective at transmitting signals between nerves, sometimes halting the signals altogether. When signals from the brain to the rest of the body are interrupted, disability results.
People with MS experience symptoms that, depending on the size, location, and number of plaques in their brain or spinal cord, can range from numbness and tingling to complete paralysis or blindness.
There are currently ten disease modifying therapies (DMTs) available that have been approved by the U.S. Food and Drug Administration (FDA). Several more are poised to hit the market soon. While these drugs have become more effective at slowing disease progression and reducing the number of attacks a person with MS might have, none are able to repair or regrow myelin once damage has been done. But that could soon change.
Moses Rodriguez, M.D., a neurologist specializing in MS at the Mayo Clinic, and his team initially identified rHIgM22, recognizing its ability to protect and stimulate the cells that make myelin, called oligodendrocytes.
“This remyelinating antibody, if successful in clinical trials and approved, would be a novel approach to treating people with chronic neurologic deficits from multiple sclerosis or other similar conditions,” said Rodriguez in an interview with Business Wire. “We are excited that this Mayo discovery is now being evaluated in people with MS to determine its therapeutic potential.”
The Clinical Trial Experience
First-in-human (FIH), Phase 1 studies are typically conducted on a small number of patients to gauge the effectiveness and safety of a drug that has already been tried successfully on animals.
For this study, which is expected to be completed by September 2014, 60 participants with MS will be randomly given infusions of either rHIgM22 or a placebo. The study’s design is “double-blind,” meaning that neither the volunteers nor the researchers know who will be given the real drug.
Participants will receive escalating doses of the drug over a 90 day period, and the infusions are given in an inpatient hospital setting.
“The day of the actual infusion I had to be admitted to the hospital for three days and two nights,” said a study participant from the Midwest who asked to remain anonymous. “Before getting the infusion, I had to give a urine sample, several tubes of blood, and have an EKG and then was hooked up to two different types of heart monitoring. I had two IV lines put in, one for the infusion and one for obtaining blood.
The study had a very strict schedule for blood draws, vitals, EKG's, EDSS [neurological exams], physical exams, and walking 500 meters. I was watched very closely for the entire time I was infused and afterwards.”
For human volunteers, a FIH study poses the greatest risk since, by design, it is the first time the new drug is used on humans. Recruiting volunteers for a FIH study can prove daunting, as people are often reluctant to risk their lives for research.
“I did the study because I felt the need to push this potential drug forward,” said the study participant. “If the data collected throughout this Phase I study indicates that it works in humans the way it did in mice, it is huge for the MS community and even possibly other central nervous system disorders.”
But moving from animal models or even FIH studies to a treatment that is FDA-approved often takes many years. “I know I may not benefit from it,” the study subject said, “but if my participation will in any way, shape, or form help someone else that is diagnosed with MS in the future not have to worry about becoming disabled or progress because we now have a drug that will repair myelin and restore nerve function, then it will be totally worth it!”
Standing Up to MS
Restoring nerve function is the holy grail of treatments for MS. For those with progressive forms of the disease, there is nothing current DMTs can do. But those who experience what is considered permanent disability from MS may still benefit from rHIgM22. Depending on how effective it is at repairing damaged nerves, these patients might one day be able to literally stand up to the ravages of MS.
For more details on this clinical study, including enrollment criteria and contact information for the study sites, visit www.ClinicalTrials.gov.