On The Potential Use Of Autologous Bone-marrow Derived Stem Cells To Treat ALS Patients

Technically, the law we all refer to as the Right to Try Act, is named the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act. Three of the four courageous patients for whom the law is named were/are ALS patients. Matt Bellina, as publicly announced, has been treated under Right to Try by a company called Brainstorm, which is in late-stage trials with an autologous stem cell product.

Amyotrophic lateral sclerosis (ALS) is a terminal neurodegenerative disease characterized by the progressive degeneration of both upper and lower motor neurons, leading to significant loss of motor function in patients and, ultimately, the ability to swallow or breathe. There are also significant psychological and emotional burdens, not just on patients but on their caregivers. ALS usually leads to death within three to five years of diagnosis.

The cause of ALS is not clear. Somewhere between 5% and 10% of cases seem to share a genetic signature, which has led this form of the disease to be called “familial.”Roughly 90% of the cases fall outside of the familial characterization, and are termed “sporadic.”

As yet, no treatment has been discovered that can reverse or stop the disease progression. The few drugs approved by the FDA to treat ALS are based on studies which reputedly show a small slowing down in the rate of progression. Riluzole, a glutamate antagonist, and Edavarone, a “free radical scavenger” and antioxidant, have both been approved by the FDA based on efficacy studies, the results of which have never been without controversy in the scientific community. In addition to their questionable efficacy, the purported mechanisms of action of these treatments are not well understood. This is not as alarming as it sounds. The mechanisms of action are unknown for many approved medicines. Furthermore, it is clear is that these medicines are safe, and that doctors have no other FDA- approved options to offer patients.

Stem Cells and ALS

Stem cells continue to be under active investigation to treat ALS. One therapy being developed uses autologous bone marrow derived stem cells (BMSCs). ( In this context “autologous” simply refers to patients being treated with their own cells.) I am often asked my opinion on these cells for the treatment of ALS. While the data is mixed and nuanced, and the mechanism of action unclear, a recent peer-reviewed study attempts a global evaluation of the potential of bone marrow-derived stem cells to treat ALS patients. Here is the abstract. You can read the entire study here.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of both upper and lower motor neurons. Patients show both motor and extra-motor symptoms. A cure is not available at this time, and the disease leads to death within 3–5 years, mainly due to respiratory failure. Stem cell therapy is arising as a new promising approach for the treatment of neurodegenerative disorders. In particular, mesenchymal stem cells (MSCs) seem the most suitable type of stem cells, thanks to their demonstrated beneficial effects in different experimental models, to the easy availability, and to the lack of ethical problems. In this review, we focused on the studies involving ALS rodent models and clinical trials in order to understand the potential beneficial effects of MSC transplantation. In different ALS rodent models, the administration of MSCs induced a delay in disease progression and at least a partial recovery of the motor function. In addition, clinical trials evidenced the feasibility and safety of MSC transplantation in ALS patients, given that no major adverse events were recorded. However, only partial improvements were shown. For this reason, more studies and trials are needed to clarify the real effectiveness of MSC-based therapy in ALS.

Stem Cells Int. 2019; 2019: 3675627.

Published online 2019 Mar 10. doi: 10.1155/2019/3675627

My Take

The authors’ conclusion, if I might paraphrase, is that while the paper catalogues a surprising amount of positive human clinical trial data, the therapy has looked more promising in animal models of the disease than in human trials so far. The relatively small number of patients, and the great variability in the benefits recorded lead the authors to conclude the therapy can not be described as “proven.” They did conclude that the cells and procedure appear to be safe. However, my own view is that there are so many sources of cells, and different ways of preparing and administering the cells, that I would be very cautious in applying this safety factor to all available sources. More on this later.

Also, the authors’ conclusions mirror my experience of the past 17 years, observing various trials and programs to treat ALS patients with all manner of cells, through all manner of routes of administration, all around the world. There is too much evidence of some benefit in a significant number of patients to be ignored, in my opinion. Unfortunately, the overwhelming majority of the studies conducted around the world have produced only anecdotal evidence, not scientific data. The authors make a valiant effort to marshal the limited data that is not strictly anecdotal, concluding that there is promise, but that more studies and trials are needed to clarify the real effectiveness. This is a fair conclusion.

I would like to add a caveat that the paper does not: That while there is ample support to say that the cells themselves are safe, the source of the cells, how they are harvested and prepared, and how they are administered, are all areas of concern for possible contamination and adverse reactions in patients. The process, which includes the sourcing and preparation of the cells, must be taken into account when analyzing the potential safety of any cell therapy. This is why, in answer to the question, “Are autologous bone marrow-derived stem cells safe?” I can only say, “they can be,” not “they are.”

And, if asked “Do they work?” My answer is also, “They can, but—” And here’s the but: The benefit appears to be transitory. There is no long-term study showing continued benefit, even in those patients who saw an initial benefit. And the benefit appears to be limited to quality-of-life issues more than a reversal of the disease progression. There is no evidence that a single administration of cells is in any way a “cure” for the disease. Bear in mind, however, that the exact same thing can be said of the approved drugs on the market for ALS. They are not a cure. They do not reverse or even stop the progression of the disease. At best, they may improve quality of life for a transient period of time.

Anyone making claims of curing ALS with stem cells is a fraud. Full stop. There is, as yet, no evidence to support this level of benefit wherever these claims are being made, whether in China, India, the US or anywhere else. Many patients do feel better after treatment, and for some, there is a meaningful return of various functions for meaningful periods of time. But all data shows that the downward progression of the disease continues. There is no evidence to the contrary.

I do not mean to diminish the value of such drugs. As many of you who read these blogs know, my own son has battled brain tumors his whole life, and anything which might improve his quality of life, even transiently, is something we always search for and analyze. When we find such an intervention we count it as a blessing, even though it is not a “cure.” So patients, and their caregivers, need to understand the truth about ALS treatment with stem cells, as well as both the possible benefits and the current limits of the technology. Right to Try is based on genuine informed-patient consent and transparency. It is based on the idea that, once armed with such information, patients with life-threatening diseases have the right to access investigational treatments, at all stages of development after Phase One safety data has been established, and to make their own treatment decisions. This is what we believe in. This is why I founded Access Hope CRO.

#AccessHopeCRO

#ALS