Safety Stem Cell Trial in ALS Set to Advance

Maryland biotherapeutics company Neuralstem has announced favorable results from the first part of a phase 1 trial to test the safety of its experimental spinal cord stem cell treatment in ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease).

The trial's safety monitoring board has given unanimous approval to advance the trial to the next stage; the U.S. Food and Drug Administration (FDA) also must grant approval before the trial can progress.

Next steps will move the treatment farther up the spine

Neuralstem's ongoing phase 1 human clinical trial is being conducted at Emory University in Atlanta, under the supervision of neurologists Eva Feldman and Jonathan Glass, and is designed to test the safety and feasibility of injecting neural stem cells into the spinal cords of people with ALS. (Glass directs the MDA/ALS Center at Emory, but MDA is not funding this trial.)

To date, 12 people with ALS have received stem-cell injections in the lumbar (lower back) region of the spine. In the next stage of the phase 1 trial, three participants ("Group D") each will receive five injections along one side of the cervical (neck) region of the spinal cord.

Although the study remains primarily a safety trial, the investigators hope that cervical injections may help with breathing and swallowing in ALS. The researchers plan to evaluate any effect of the experimental treatment on trial participants' motor function loss, respiratory function and ALS Functional Rating Scale scores.

Members of the clinical trial research team have been pleased with the "smooth progress" of the trial thus far, Feldman said, in a press release issued by Neuralstem. Feldman noted the team is "particularly excited" to advance to the next stage, once FDA approval is received.

Recruitment of 3 people with ALS to comprise "Group D" is under way. Eligibility criteria can be found at the Emory ALS Center trial website.

Trial participation does carry some risks, including a potential harmful immune system reaction to the injected cells; the need to use immunosuppressive medications in order to tolerate the injected cells; and the possibility that the spinal cord could be damaged by injections.

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 Understanding Clinical Trials and Being a Co-Adventurer, which is about neuromuscular disease clinical trials. To see a continuously updated database of clinical trials, go to www.clinicaltrials.gov.

The trial has a growing record of favorable results

This first U.S.-based trial of neural stem cells in ALS opened in January 2010. As of June 2010, four people with ALS had received stem cell injections into their spinal cords. Responses of the first six participants who received the experimental treatment were judged to demonstrate adequate safety, allowing the trial to proceed, and at the American Academy of Neurology meeting in April 2011 Feldman presented interim safety data that showed there were no unresolved serious adverse reactions in the first nine participants to undergo the stem cell implantation procedure.

Minor adverse events have included temporary pain at the injection site and problems connected to immunosuppressive medications used to help patients tolerate the transplanted cells.

Trial design slowly increases risks

The phase 1 Neuralstem trial is progressing through increasing levels of risk in 18 people with ALS, depending on safety results at each stage. The levels of risk correspond to trial participants' disease severity, and the number and location of injections into the spinal cord.

• The first six participants already had lost the ability to walk when they entered the trial. In this group, the first three received five injections into one side of the lumbar region of the spinal cord; the second three each received 10 injections into both sides of the spinal cord.
• The second group of six participants were at an earlier stage of ALS than the first, and all were still able to walk. They all received injections into the lumbar region of the spinal cord, with the first three receiving injections on one side and the second three receiving injections on both sides.
• The upcoming final stage (currently awaiting FDA approval), will include six people with ALS who are able to walk unassisted, and who also have good respiratory function. Injections will be administered to the cervical region of the spinal cord. The first three participants each will receive five injections along one side of the cord, and the final three will receive injections to one side of the neck and to both sides of the lower spine.

A great deal about Neuralstem's injection procedure and the effects of the transplanted cells in the body is likely to be learned from the current trial, all of which will inform future stem cell trials.