Part 1

BRAINWeek: Background Information on ALS

Dr. Bedlack vividly recalls how a patient described ALS to him:

The day you told me I had this, it’s like you put me in a box. Every day the box gets a little smaller on all sides and it further restricts what I can do. One day I know it’s going to get so small and tight that it’s going to choke the wind right out of me, and I’ll die.

ALS, amyotrophic lateral sclerosis, used to be known as Lou Gehrig’s disease; the New York Yankee baseball player died from ALS in 1941. It was first described in the late 1800s by a neurologist named Jean-Martin Charcot as a degenerative disease of motor neurons, the wires which connect the front of your brain where you send decisions to your muscles that carry out your actions.1 As this disease progresses people become disconnected from their muscles and eventually lose the ability to walk, feed or dress themselves, speak, swallow, and eventually breathe. It happens quickly. On average, the trajectory is about 3 years from symptom onset until the time tough decisions—whether the patient wants to be attached to a breathing machine in order to stay alive—need to be made.

Thankfully it’s not a very common disease. In the US there are approximately 20,000 people living with ALS. There is about 1 in 50,000 new cases per year. By those numbers it seems pretty rare, but the lifetime risk of ALS is about 1 in 400, and that isn’t that “rare.”2

ALS Treatment Evolution

“I saw my first person with ALS when I was still a resident at Duke, in the late 90s,” says Dr. Bedlack. “I remember thinking this is the most amazing and most terrible disease I’ve come across. I could not wait for my preceptor to come in and explain how we were going to fix it. He came in and said ‘Well, this is what it is called. We don’t know why it happens and there’s

nothing really that we can do about it. The patient has to go home and get his affairs in order.’ He then just got up and left. I could only imagine how a patient and their family would feel. There’s got to be a better way.”

Bedlack spent the rest of his training, residency, and neuromuscular fellowship trying to understand the disease and discover what people around the world could offer. “I travelled, visited clinics, and I tried to take the best practices back to Duke. I built what I think is one of the largest, most comprehensive ALS teams in the world.” There are 20 team members, everyone an expert in different parts of the body: neurologists, speech therapists, nutrition therapists, respiratory therapists, pulmonologists, physical and occupational therapists, a social worker, nurses, and nurse practitioners. Every few months, a patient will spend the day with the team, which goes over them from head to toe. If anyone sees that ALS is trying to take something away from the patient, the team is trained to offer evidence and experience based options.

People leave with a list of things they can do, and these things add up. Quality of life is better and some data suggests length of life is significantly better than it was 20 years ago.3 Dr. Bedlack said, “We built a research program to give people hope, with genetic studies, biomarker studies, epidemiology studies, and industry-funded clinical trials. The research that I do lead in some unexpected directions, suggested by patients. When I began my career, I did not know how many patients would be interested in what I call alternative and off-label treatments. Things were advertised, usually on the internet, to slow, stop, or reverse ALS without what most scientists would consider to be very good evidence. There are tens of thousands of these products, and more every day. Nobody, in terms of doctors and scientists, was interested in these products. But since patients were, and there was no place for them to find objective information, I built one. It’s called ALS Untangled.”

The website, ALSuntangled.com, has a virtual bulletin board for suggestions, things people have heard about that might work for ALS. The community can vote on which ones they think are most interesting. When something gets enough votes, Dr. Bedlack’s team takes it on. “We have standard operating procedures to do an objective review on these ideas. We crowdsource it and eventually publish it by a free Open Access method. So, now if a patient goes to a clinic anywhere in the world and says, ‘I heard about coconut oil or curcumin or acupuncture’ there are articles and summaries designed for nonscientists. We hope to help people make more informed decisions. If they still want to try some of the products that we reviewed unfavorably, that’s okay.”

Out of ALS Untangled, Dr. Bedlack discovered there are people around the world who recover from ALS. “This was never told to me, it’s not in any textbook,” he says. “There are articles scattered in literature back to the 1960s about this.4 We’ve built a whole research program, studying what’s different about these people in terms of their demographics, or disease characteristics, or genetically in terms of their RNA, or protein expression, or their microbiome.”

Dr. Bedlack and his team examined what survivors were doing and taking. They did trials to see if they could reverse anyone else’s ALS. “Most pharmaceutical-sponsored trials have very narrow inclusion criteria because they’re trying to homogenize a noisy disease to look for a small signal. The trials I put together have a wide inclusion criteria: almost anybody can participate. I’m not looking for a small signal. I’m looking for an ALS reversal.” These trials don’t involve placebos; they have historical controls and in-person visits are not required. Dr. Bedlack continued, “The things I’m looking for are so big that I can teach you how to help me find them by phone and video visits.” The trials are popular and fill up quickly. The team is awaiting the results of a trial examining the effects of theracurmin, a form of curcumin, a molecule found in spices. It has plausible mechanisms by which it might help a person with ALS. It has more ALS reversals associated with it than any other product.

The Importance of Education

“My field is moving fast. It seems every time I turn around there’s a new important paper or a trial that was positive. It seemed like for decades, nothing was happening and now it seems like it’s exploding. We have two drugs that come in different formulations. We have a third drug that’s in front of the FDA. There’ve been multiple recent trials that look like they could, in the very near future, be going up in front of the FDA. Science is moving at an unprecedented rate and it’s really important to get out there and hear from experts. I’m lucky. I’m at the Duke University Medical Center where I’m surrounded by people at the cutting edge of their field. There are conferences every day that I can attend and hear about breakthroughs, but not everybody has that. Some people are in a private practice setting where most of their day is spent seeing patients. If they want to be on the cutting edge, they must hear from people across different specialties.”

Dr. Bedlack’s goal is that the nurse practitioners, PAs, general neurologists, and others who come across a person with ALS can offer hope, as opposed to being told, “There’s nothing you can do.” Education is vitally important: “There are things we can do now, not only for ALS, but for a lot of diseases that we couldn’t do 10 or 20 years ago. For some people, the CME is required. While I can get my required CME at grand rounds (which happen every week at Duke) for some, lectures such as those are not as accessible. You have to go and get CME. You can’t renew your license in most states without CME.” Stay cutting edge via education.

1. Sanders: J Am Podiatr Med Assoc. 2002 Jul-Aug;92(7):375-80. doi: 10.7547/87507315-92-7-375.

2. Unmet needs: A brief history of ALS and its sparse pipeline. . 2021. https://www.pharmaceutical-technology.com/analysis/history-of-als/. Accessed Aug 19, 2022.

3. Peseschkian T, et al. A Nation-Wide, Multi-Center Study on the Quality of Life of ALS Patients in Germany. Brain Sci. 2021 Mar 14;11(3):372. doi: 10.3390/brainsci11030372. PMID: 33799476; PMCID: PMC7998410.

4. Mangelsdorf I, Walach H, Mutter J: Healing of Amyotrophic Lateral Sclerosis: A Case Report. Complement Med Res 2017;24:175-181. doi: 10.1159/000477397