Efforts to find a cure for ALS, the fatal neurological disease, was brought to public awareness through last summer’s social media-fueled “ice bucket challenge.”
In January, JAMA Neurology, a publication of the American Medical Association, published the results of a clinical trial of a new treatment protocol developed by Hadassah Medical Organization (HMO) in partnership with the U.S.-Israeli biotech company BrainStorm. We caught up with the principal investigator of the trial, Dr. Dimitrios Karussis, HMO’s senior neurologist, to discuss how the treatment works, the scope of the clinical trial and what the results tell us about the potential for finding a cure for ALS. The interview was conducted via email.
Why is ALS such a hard disease to treat?
An estimated 30,000 people in the United States or 450,000 worldwide are affected by ALS, which progressively steals a person’s ability to walk, to speak, to swallow and, eventually, to breathe. We still don’t know the cause of this disease, but I am hopeful that someday we will.
What happened to facilitate development of this new treatment?
Over the past decade, my team at the Hadassah Medical Organization has initiated clinical trials with stem cells in the hope of slowing and reversing the progression of ALS. Five years ago, we collaborated with the U.S.-Israeli biotech company BrainStorm Cell Therapeutics to bring the stem cell therapies to the next level. Brainstorm developed NurOwn®, a new (and patented) technique for harvesting, culturing and enhancing stem cells from a patient’s bone marrow while our team developed and advocated a new way of injecting the enhanced stem cells into the patient’s cerebrospinal fluid.
How did your clinical trials work and what were the results?
In total, 26 ALS patients participated in our trials. All of them had progressive disease during the months preceding the study and significant neurologic disability that involved their motor function, their respiratory function and their ability to speak and swallow. Of the 26 patients in the study, six had the enhanced stem cells injected intramuscularly [into a muscle] and 16 were injected intrathecally [into the spinal cord]. Four additional patients did not complete the follow-up [portion of the study] for various reasons.
The results showed that the procedure was safe and well tolerated over the three-year study period without any serious adverse events related to the treatment. Despite the fact that the primary aim of our study was to evaluate the safety of the procedure, we did observe impressive clinical effects in various parameters of the disease progression and disability, providing strong indications of clinically meaningful beneficial effects.
Does this treatment cure ALS?
Close to 90 percent of the clinical trial patients who had the enhanced stem cells injected into their spinal fluid responded to the treatment, showing an improvement of at least 25 percent in the rate of progression of either their respiratory function or their general motor disability. (The patients who received intramuscular injections generally did not respond, except for a local beneficial effect on the muscles of the limb that was injected.) In some of the patients, the disease not only stopped progressing, but there was a noticeable improvement in their neurological functions. The fact that the study had a rather small number of patients and was open [everyone received the real treatment, as opposed to placebo-controlled, double-blind studies] complicates interpretation of the data, but for a disease such as ALS, I believe that the improvement shown by the patients is beyond the range of a putative placebo effect. While our study cannot provide the proof of a cure, it is the first step in a long process that we anticipate will lead to a successful treatment of ALS.
Last summer’s “ice bucket challenge” raised $100 million for the ALS association for research. Did that funding have an impact on your study?
Hadassah in the U.S. and Hadassah International (as opposed to grants from foundations or industry) have been the primary source of all of our funding for research, patient care, and capital projects at the Hadassah Medical Organization in Jerusalem. While the ice bucket challenge had no direct impact on our research work, which had been progressing over the course of the past decade, it did an incredible job of raising awareness for the ALS disease worldwide, so in that sense, it was very beneficial.
What other diseases could this research affect?
I believe we are in the beginning of a new era in the field of regenerative medicine for the central nervous system in general, with relevance to many similar diseases of the brain such as Alzheimer’s, multiple sclerosis, Parkinson’s disease, stroke and spinal trauma.
Is there anything else you want to add?
For me, the most important part (and the major source of my excitement) is not only the “numbers” but what lies behind them, the personal stories of the treated patients, many of whom came back to the follow-up meetings with improvements in their everyday lives and functioning and a smile on their faces.
The most compelling and touching of such stories was that of a 22-year-old Israeli soldier, who was diagnosed with ALS during his army service and had a very fast progression. Following the stem cell treatment, the disease completely stopped progressing and he had a significant improvement in his ability to speak and in his motor function of the hands. This improvement lasted for at least one year and then he received an additional treatment on a “compassionate basis,” [when a seriously or terminally ill patient receives an experimental drug or therapy], which resulted in a similar, and even an enhanced, beneficial effect.