Since then, the response from the ALS community has been extremely touching. Regrettably, I have fallen far behind in answering the requests from patients and their families, but I want to start making amends by taking this moment to update everyone on several developments in this field.
In crafting this summary, I should note that I am an experimental biochemist and not a physician or medical practitioner. I have no direct involvement in the development of these clinical trials, including patient enrollment. This is a source of information that I hope you will find useful – nothing that I say or write can be considered medical advice.
Can a micronutrient really work in ALS ?
Last year, we published the results of an experiment that lasted nearly three years. It was a carefully organized experiment showing that a compound containing copper, an essential metal micronutrient, was remarkably protective in multiple mouse models of ALS (aka Lou Gehrig’s disease). We were able to extend the lives of some of these animals from a few weeks to nearly two years.
Linus Pauling advocated the importance of the right micronutrient at the right time and place for effectively promoting health and preventing disease. In our experiments, we found that copper is important, but alone was not enough. Administration of free copper – like that found in supplements – did not bring about any success. In fact, taking too much copper is harmful and dangerous.
The key to our success turned out to a special chemical carrier called ATSM: A molecule that transports copper into the spinal cord – the place where the copper is the most needed to treat ALS, and effectively preventing other tissues from experiencing the negative effects of excess copper.
Despite these successes, the scientific community is very skeptical of these findings. Rightly so – nobody has previously repeated any successful treatment in ALS models. However, our results with copper-ATSM have now been confirmed independently in both Australia and Boston.
The next steps are to develop this compound for use as a drug in humans, as you can read about below. As with any drug, especially in use for treating ALS, the odds are still very small that this will translate into clinical success.
That said, our research goal is not to develop new drugs for ALS, but rather to understand the role of biological oxidants in this disease, and one similar to it. From a deep understanding of the underlying causes, my research has identified multiple targets for therapy – pointing the way to the next generation of clinical trials in ALS. For example, we have spent the past three years looking for a better version of Copper-ATSM.
In writing this, I thank two special donors to the Linus Pauling Institute to whom I am grateful. They have supported my work when no funding agency would contribute to the cause. We hope that their generous contributions will ultimately yield success.
My research is also currently supplemented by the Department of Defense, specifically the ALS research made available by the lobbying efforts of the US ALS community through the Congressionally Mandated Medical Research Program.
Phase I Safety Clinical Trials
Procypra, the company I reference in my first letter, is taking the lead in developing Copper-ATSM for treatment of Parkinson’s disease and ALS.
Their Phase I trial is now recruiting, and found on ClinicalTrails.gov under identifier NCT02870634. This is the first step in the long and often tedious process of new drug development. However, it is an important step, as it helps us understand the dangers of using this compound.
As it is a Phase I trial, it is not intended to test for a ALS treatment. Instead, it focuses on the investigation of drug safety. The Phase I starts with small, but escalating, doses that will test to see how well the drug is tolerated. At present, Phase I trials are to be conducted with sporadic and familial ALS patients.
Many patients and families who I have talked to question the need for such a trial and the loss of very valuable time. I understand the frustration and aggravation at the process, but I want to make one thing clear – despite a diagnosis of a terminal disease, there is a lot to lose from unproven treatments. Please be particularly suspicious of claims of cures from detoxification therapies or stem cell approaches.
As I said above, high amounts of copper are toxic, especially in the brain and the liver. While the ATSM compound holds on to copper tightly and prevents this toxicity in the trials in mice and rats, in humans this may be completely different.
The wrong amount, timing, or route of administration, or the presence of an unwanted contaminant could destroy the liver or kidneys in a day or a week. Certainly, an awful and painful death to endure. Thus my words of caution.
Particularly worrisome is that some people are particularly susceptible to the drug. The therapy might work well in a handful of patients, but the same dose may be fatal to others. Many tests are currently being conducted to avoid this possibility, carefully watching for problems early, and, hopefully, minimizing immediate and irreversible damage.
This is a major reason that these clinical trials take so much time to organize and conduct: to keep everyone safe.
However, I have already heard promising reports from the trial: very small doses of the compound are well-tolerated and investigators plan to escalate to higher dosages. Those receiving a low dose are continuing treatment, and we can only hope they continue to see no adverse events.
Other potential ALS drugs.
I would like to make you aware of two other drugs that are further along the pipeline for approval by the FDA. One is Masitinib, by a French company named AB Science, and the other is Edaravone, a product of Japan’s Mitsubishi Tanabe Pharma. Both are currently now being reviewed by the FDA for approval of use in the United States.
Masitinib is now sold in a veterinary formulation for the treatment of mast cell cancer. It is a protein kinase inhibitor that is currently undergoing a phase II/III clinical trial to find its efficacy in ALS. My close collaborator and friend, Luis Barbeito in Uruguay, had a significant hand in developing the rationale for its use in ALS patients.
Masitinib is approved by the FDA for “compassionate use”. This means that the drug – though not fully approved – is used outside of a clinical trial to treat a patient with a serious or immediately life-threatening disease or condition who has no satisfactory alternative treatment options. Access is allowed only by request of a physician and FDA review and authorization, and also the permission from the drug manufacturer.
Edaravone (also called Radicut) is another compound currently approved in Japan for the treatment of stroke and ALS. A synthetic free radical scavenger, edaravone works on reducing protein nitration – a mechanism in ALS that I have been studying for over 20 years.
A company called Mitsubishi Tanabe is currently seeking approval by the FDA for the use of Edaravone in the United States; other clinical trials are currently being conducted for this drug in ALS patients in Europe.
Looking to the future.
In summary, there has been more progress in the past year in the treatment of ALS than I have seen after working in the field for 25 years. The progress on getting Copper-ATSM to clinical trials has been rapid compared to most drugs, but still far slower than it needs to be. Now that we have real successes in treating this awful disease, it opens the road to even more exciting and substantive successes.
With best regards,
Joe Beckman, Ph.D.
The Burgess and Elizabeth Jamieson Chair in Healthspan Research, Linus Pauling Institute
University Distinguished Professor of Biochemistry and Biophysics
Director, Environmental Health Sciences Center
Oregon State University, Corvallis, OR