Updated October 20, 2017

Elsa Tremblay from l’Université de Montréal studies ALS because of a personal connection.

Is there anything in particular that drew you to studying ALS?

I went into ALS because my father died from ALS, and also my grandmother. So it’s pretty clear that ALS is running in the family…probably a genetic cause. So this is really the motivation that has driven me to the study of this disease. And this is why I’m putting all my effort to try to unravel the mechanisms and understand the disease and try to find a cure for it.

Could you tell us a bit about your ALS Canada funded research?

My research is focused on the neuromuscular junction. This is the connection between the motor neuron and the muscle. So for example, when you want to perform a voluntary movement, then the command is traveling by the motor neuron into your spinal cord, and then finally will reach the muscle in order to perform the movement. But what happens in ALS is that the connection between the motor neuron and the muscle is progressively disconnected. So it’s like a bridge that disintegrates. So the message can no longer be sent. So I’m working to understand what’s making it happen, why is this disconnection and malfunction happening, and trying, maybe, to find therapeutic strategy to work on it.

If someone living with ALS were to ask you where we are at right now with ALS research, what would you tell them?

Right now I think we are in a great spot. Because there are several clinical trials ongoing. Some of them are at Phase 2, Phase 3… We have the Masitinib, Pimozide…We have other molecules, as well. There’s also a different strategy to interact with the proteins that are misfolding there, that are not working properly. So I think this is a very interesting moment for now, because we have hope.

We have therapeutic molecules that actually are pretty advanced in the process. So I think people can really have hope and can be confident that we, at some point, will find a cure. What I think is that we may not have only one cure for ALS, but depending on the genes involved, or depending of the various forms of the disease, we will have several cures, and we will be able to have a treatment based on the specifics of every patient.

Is there anything you would like to say to donors who are directing their donations to research?

Funding is making a great difference. I can tell you that. ALS is a very complex and difficult disease to understand. We have discovered several genes involved, several mechanisms. So it’s really a team effort to be able to unravel pathogens and mechanisms in the disease process. So I think funding allows us to have money for various projects. To really diversify the investigation we can do. And this is really the key for this team effort to be successful, and to allow us to find a cure for the disease.

I also think that having funding is also great motivation. It gives you a feeling that the ALS community supports you. It gives you—”I trust in you, I know what you’re going to do is going to make a difference.” And this is really a strong motivator, and it helps us to even work harder.

Sometimes when you get your first funding, it really helps you. But it’s just a first step. Because after that, you can get other funding from other sources. For example, in the lab, we got the Discovery Grant for two years. But then it allowed us to have a four year grant at the CIHR. So then we can continue our research project.

So it’s like when you plant a seed, and then it’s always surprising how tall it can grow. In ALS, every penny counts, every dollar counts. I strongly encourage you to help us plant a seed and watch it grow. And I think it is this team effort that is going to allow us to make ALS a treatable disease.

ALS Canada Virtual Research Forum:

Update: Elsa Tremblay was one of more than 20 speakers who participated in the ALS Canada Virtual Research Forum in August. You can listen to her full presentation online here.

Updated October 20, 2017

Very early in his medical training, Dr. Lawrence Korngut was introduced to the concept of ALS. “As a neurologist, I have always been very interested in the physical exam and ALS is the perfect example since the diagnosis is made entirely by physical exam,” said Dr. Korngut in an interview with ALS Canada. “I am continuously inspired by people living with ALS and their families. ALS is a disease of weakness, but these are the strongest people I know.”

Dr. Korngut moved to Calgary in 2007 where he has continued a relentless pursuit to find new treatments and interventions to help people living with ALS. He is a neurologist and clinical neurophysiologist at the Calgary Neuromuscular Clinic and the Director of the Calgary ALS and Motor Neuron Disease Clinic.

The Pimozide Potential

The discovery that the drug pimozide might have an impact on slowing disease progression began with worms in a Petri dish on the lab bench of Dr. Alex Parker, a researcher at the University of Montreal. Dr. Parker genetically engineered worms with a human form of ALS and tested them with a battery of drugs to look for a positive impact on motor neuron (health and function. He found a bunch of antipsychotic drugs that would work, but pimozide seemed to be the most effective. He shared his results with other researchers who then explored pimozide in other animal models.

At the 2012 ALS Canada Research Forum, Dr. Korngut heard Dr. Gary Armstrong present his positive findings about pimozide in zebrafish that had been altered with a human form of ALS. A postdoctoral student at the time, Dr. Armstrong had been working with lead researcher Dr. Pierre Drapeau at the University of Montreal. Dr. Korngut thought the next step would be to translate this preclinical research. “I thought, since pimozide is already an approved drug that we know a lot about, is available, and costs about $0.09 per pill, a clinical trial in human volunteers seemed like the next logical step,” he said.

Pimozide is an older drug, typically used to treat schizophrenia. “It was used at high doses and had some notable side effects, so it has mostly been replaced with newer generation drugs today,” Dr. Korngut explained. “We don’t know exactly how pimozide works, but the evidence so far suggests that it strengthens the electrical connections between nerves and muscles, allowing them to function better,” he continued. “In animal models, there seemed to be some promising signs of effect on the disease, but we don’t know yet if the drug will work the same way in humans.”

Translating Preclinical to Clinical Research

Since 2013, Dr. Korngut has been leading a ground-breaking, first-in-human clinical trial for pimozide at the University of Calgary among 25 volunteers with ALS. He is investigating whether the drug can slow disease progression and exploring how much medication needs to be taken to have an effect. The trial opened in April 2015 and is now complete. The Quirk Family in Calgary and the University of Calgary provided funding support, which is noteworthy since trials for existing, inexpensive drugs are not usually of interest to large pharmaceutical companies.

While the small number of study participants makes it impossible to draw any concrete conclusions, the results are promising. “We found the dose that is most likely to be best tolerated among people with ALS, a lower dose than is used in other conditions and we have some preliminary evidence that pimozide is helpful.” said Dr. Korngut. “At this point, though, people with ALS should not use the drug yet until we study it further in a larger number of volunteers as we don’t know that it is helpful but we know that it is associated with significant side effects.”

Plans for a larger scale trial are already established. After getting the first trial started, Dr. Korngut collaborated with Dr. Lorne Zinman at the University of Toronto. They applied to ALS Canada for funding and were successful in securing an ALS Canada – Brain Canada Arthur J. Hudson Translational Team Grant in 2015, a total of $489,857, to support the study. Health Canada and the ethics committee at the University of Calgary are currently reviewing the clinical trial protocol that will test pimozide in 100 volunteers with ALS in eight clinics across Canada. If the proposal is approved, Dr. Korngut and his colleagues would be able to begin recruiting patients, possibly as soon as autumn 2017.

“There is a lot of reason to be optimistic about the research going on in the ALS community right now. That’s a testament to all the people with ALS and their loved ones who volunteer in clinical trials as well as the donors, patient organizations and dedicated researchers,” said Dr. Korngut. “The pimozide story is a great example of a treatment identified through very fundamental research that is being explored in human clinical trials because of funding by ALS Canada and Brain Canada. Without their contribution, this research would not be happening.”

ALS Canada Virtual Research Forum

Update: Dr. Korngut was one of more than 20 speakers who participated in the ALS Canada Virtual Research Forum in August. You can listen to his full presentation online here.

A group of ALS clinicians across the country is developing Best Practice Recommendations to set a common standard of care for Canadians living with ALS. Dr. Christen Shoesmith of the London Health Sciences Centre explains. She will be speaking about the Canadian ALS Best Practice Recommendations at the Virtual Research Forum on August 9. Read more and register here.

Why is it important to have best practices in patient care?

In Canada we really feel that it’s important that each patient, no matter whether or not they live in Nova Scotia versus Quebec or BC, all get the same type of care. And that they have the same access to that type of care.

Best practices are extremely important for advocacy for our patients, and establishing what is a standard of care across the country. Without practice guidelines in place, there may be inconsistencies about patient care across the country, or between provinces. But it’s very difficult to decide which province is doing the best. And so if we have a standard set between the provinces, it’s very easy to say a province is not providing the best care for the patients because they’re not meeting the standard that we have set. And providing these Best Practice Recommendations will allow us to know exactly what is the standard, what is the measure at which all the clinics should be measured and all the patient care should be measured against. That will help in both providing excellent care to the patients because the patients deserve the best and most appropriate care for their disease, but also to advocate, to make sure that they have the resources in place to have that best care.

Setting a baseline will make sure that patients get that standard of care for their disease. The other thing is it also speaks to the ability to change, and that we need to have a process that we can adapt and continually review to make sure that we don’t need to make changes as things change.

Right now, we only have a single medication that is approved by Health Canada, but having a guidelines process in place and a group of people that look at the guidelines regularly, will make sure that if there is a new medication that is introduced, that we can adapt that quickly, and so that we can make sure we advocate for our patients to get new treatments as they become available.

One of the big things that we’ve got within our provinces is that we do have a rural versus urban distribution, and so these guidelines will also make sure that those patients that live in northern communities, that may be remote from some of the ALS centres, will get the same type of care. Because even if that patient is unable to travel to the centre because of the geographical distance, their physicians in their local centre will know what the standard of care is so that they can try their best to provide that standard of care for the patient in their local community.

Who has been involved in developing the Best Practice Recommendations? 

We have a number of ALS clinicians across the country that have been involved. We try to do our best to have a geographical representation of clinics across the country. We have someone from Nova Scotia, from New Brunswick all the way over to Alberta. They’re all ALS clinicians in clinics, so they’re either the director of the clinic or a physician that works in the ALS clinic. So we do have a broad representation. And at this time, we have nine active clinicians on the committee that are working at these guidelines.

These guidelines are based on our real-life experiences with how we treat patients and how we manage those patients in our clinics.

How has the development of these Best Practice Recommendations been funded?

We are very, very thankful that ALS Canada has decided this is a very important endeavor, and they recognize that fact for the last few years. And they have supported our project. And we’re very grateful for their support because without it the guidelines would not have been produced.

ALS Canada Virtual Research Forum

Update: Dr. Shoesmith was one of more than 20 speakers who participated in the ALS Canada Virtual Research Forum in August. Some presentations from the forum are available online here.

Updated October 20, 2017

Dr. Michael Strong has spent his career as a clinician scientist researching ALS with a determined curiosity and keen attention to new learning in the field. Over the years, people living with ALS and their families have been an ongoing source of inspiration to him. “The toughest thing in life is to diagnose someone with ALS because there is so little we can do to stop the disease,” said Dr. Strong in an interview with ALS Canada. “But people and families living with ALS are the most rewarding group to work with. It’s a real privilege that I absolutely enjoy.”

Career Signposts

Several events in his early training led to Dr. Strong’s decision to focus on ALS. As part of completing his medical degree at Queen’s University in Kingston, Ontario, he decided to do an elective placement with a neuromuscular group in Copenhagen, Denmark. Before departing overseas, he examined a person with ALS in a hospital setting and thought that would be his last opportunity to see someone with the disease. As fate would have it, his placement in Copenhagen turned out to be the only ALS treatment center in Denmark, which gave Dr. Strong the opportunity to learn from many more patients as well as clinicians.

When Dr. Strong returned to Canada, he completed his neurology training at Western University in London, Ontario, under Dr. Arthur J. Hudson, a co-founder of ALS Canada. “Both Arthur and the neuropathologist recognized that I had a real interest working in neuropathology, allowing me to do a lot of work that residents wouldn’t normally get a chance to do,” said Dr. Strong. Neuropathology is the scientific study of brain and spinal cord tissue to understand disease processes.

After he had heard Nobel Prize winner Dr. Carleton Gajdusek from the National Institutes of Health (NIH) in the United States present findings on a particular form of ALS that occurred with a much higher prevalence in a Western Pacific region, Dr. Strong was intrigued. He went to the NIH to complete a post-doctoral fellowship in ALS and then returned to Western University to continue working in the field.

Today, Dr. Strong is Dean of the Schulich School of Medicine & Dentistry, Distinguished University Professor in the Department of Clinical Neurological Sciences and holds the Arthur J. Hudson Chair in ALS Research at Western University. He also maintains a clinical practice focusing on diagnosing and treating people with ALS. One of his key areas of research over the years has been to explore the relationship between ALS and frontotemporal dementia. ALS Canada has provided past funding for Dr. Strong’s work in this area.

Inquiries to Insights: Frontotemporal Dementia in ALS

Frontotemporal dementia is a group of disorders caused by nerve cell loss in the frontal lobe of the brain, which plays a large role in voluntary movement and cognitive functions including decision making and speech, or the temporal lobe, which is responsible for processing sensory input. While the association between frontotemporal dementia and ALS is distressing, Dr. Strong believes that people and families facing an ALS diagnosis need to be aware.

“It’s a big relief for patients, families and caregivers to know that dementia-associated behaviours are not their fault but are a result of the disease,” explains Dr. Strong, who notes that the association between ALS and frontotemporal dementia has recently led to the identification of 4 drug targets that may benefit lots of people in the future.

In the early 1980s, it was believed that dementia in ALS was exceedingly rare, occurring in about 15 per cent of cases. Dr. Strong, however, found that conclusion at odds with what he and others were seeing in the clinic: that one in four people with ALS had problems controlling their emotions, such as experiencing spontaneous laughter or tearfulness, which suggested that a form of dementia might be associated with the disease. Dr. Strong brought together a group of colleagues and published the first paper that challenged the assumption that there is no dementia associated with ALS.

Following that insight, he and his team investigated further. They knew from other scientists’ published work that one of the problems sometimes associated with ALS is a decline in the ability to form words, a process called verbal praxis, where the brain makes the connection between thoughts and speech. Using an advanced imaging technique called magnetic resonance (MR) spectroscopy, Dr. Strong and colleagues examined post-mortem tissue and found that people with ALS who had developed frontotemporal dementia had lost neurons in the same area of the brain responsible for verbal praxis.

After a further series of investigations, Dr. Strong and his team of researchers discovered that the underlying culprit is the deposition of tau protein. Normally, tau is critical for maintaining the structure of a neuron, but when harmful cell mechanisms release it, and it becomes free-floating, it can clump and form tangles that cause interruptions in neural pathways. “We published a paper showing that there is a very specific pathology with tau protein. For the last 15 years, we have been proving the change we saw in tau is not an accident. We know exactly what that change is and how it triggers neurons to die,” said Dr. Strong.

“Today, we know that some form of frontotemporal dementia in ALS is very common. The full spectrum includes mild impairment that may not be noticeable or cause problems, dysfunctional frontotemporal syndrome with behavioural or cognitive impairment, and full dementia, which affects about 15 percent of cases. All of those pooled together are found in well over half of ALS patients,” said Dr. Strong. This learning is critical since people with ALS who exhibit behavioural or executive functioning difficulties, such as issues with planning, reasoning and problem solving, have a least a year less survival time. Moreover, he added, “We know exactly what causes tau protein deposition. We can reproduce it and we have identified four different drugs that can completely stop the process.”

Dr. Strong and colleagues recently published a paper describing how the tau protein mechanism occurs in ALS as well as other dementias that involve excessive deposits of tau protein, including Alzheimer’s disease, vascular dementia and Parkinson’s disease.

Soon, a large, Canadian multicentre trial investigating similarities and differences in five neurodegenerative diseases known for tau protein deposit issues, will report on results. Dr. Strong is primary investigator of the study, called the Ontario Neurodegenerative Disease Research Initiative (ONDRI), which involves more than 50 investigators at 13 clinical trial sites and 600 participants. The diseases under investigation are ALS, Alzheimer’s disease/mild cognitive impairment, Parkinson’s disease, frontotemporal lobar degeneration and vascular cognitive impairment (from a stroke). ALS Canada is one of four patient advocacy groups serving in an advisory role.

Dr. Strong’s relentless work moving from inquiry to insight and repeating that process throughout his career has produced a series of new scientific discoveries in the ALS field. “It’s about doing experiments at the right time: paying attention to things changing in the field; listening to world experts; and every once in a while, walking away and saying, ‘Hmmm…maybe we’re wrong. Maybe we should be looking at this instead.’”

Dr. Strong acknowledges the important role that donors play in making ALS research possible, noting that in 1993 there were only a few researchers in Canada funded to work on ALS. “The transformation in ALS research led by ALS Canada over the last decade has provided a solid foundation for ALS research funding,” he says, “so investigators like myself know we have multi-year funding to move forward.”

ALS Canada Virtual Research Forum

Update: Dr. Michael Strong was one of more than 20 speakers who participated in the ALS Canada Virtual Research Forum in August. You can listen to his full presentation online here.

During his presentation, Dr. Strong provided an overview on frontotemporal dementia in ALS. Two messages he hopes people with ALS will take away from his talk are:

 

Updated October 20, 2017

Bastien Paré from l’Université Laval has been studying ALS for more than five years. We spoke with him about his research and the future of ALS in Canada.

Can you tell us about your ALS Canada-funded research?

I’m quite different from most people that are working on neurons, and trying to understand the neurodegenerative part of ALS. I’m working on ALS in the skin of patients. So we think that the skin might be a good human model to study ALS, and then discover new biomarkers, or understand how the disease works, and even try new drugs for possible treatment of the disease.

How did you get involved in ALS research?

At first, I was studying Alzheimer’s Disease, and then going on about some proteins that could be related to ALS. Then I was able to meet people that were affected with the disease. And then meeting people affected with this terrible disease that is ALS, then it kept me going about studying ALS and trying to discover something about it and understand more about the disease.

What we aim to do is to be able to discover biomarkers that could help in the pre-diagnostic part of the disease. So, if we are able to detect ALS before the apparition of symptoms, and then neurodegeneration, then when there is a drug available for those patients, we’ll be able to give this drug earlier. So we think it might be able to delay the development of ALS in those patients, or related ones.

If someone living with ALS were to ask you where we are at with ALS research today, what would you tell them?

We think there’s still a lot to do about ALS, but we’re working on understanding how the disease works so we can pinpoint specific drugs that would help treat the disease. So right now, where we are, I guess, is we’re trying to better understand how the disease works so we can test drugs that could be specific to ALS patients, and then be able to treat this terrible disease.

What do you see as the difference-makers in ALS research?

I think clinical trials and people affected with ALS participating in those trials are very important, because without them, those drugs couldn’t be tested. And then we wouldn’t know if they work or not. We know it’s hard for ALS patients to get treated. Sometime those treatments are hard to live with. But this is very essential to the discovery of drugs that could work for all ALS patients, and then delay the development of the disease, or even stop it.

Is there anything you’d like to say to donors who help make your research possible?

Of course, it’s important to donate to ALS Canada or patients. Because without this money, well, it would be hard for us to use the newest technologies to be able to study ALS, how ALS works in patients. And then, as I said, try new drugs and pinpoint drugs or chemicals that could be very good treatments to delay or stop the progression of the disease. So this money, I guess, is very important to add finances to those labs that maybe don’t have it. Or students that still need this money to buy new equipment and do new techniques that, I guess, are very important for discoveries of those drugs and supporting ALS patients.

ALS Canada Virtual Research Forum

Update: Bastien was one of more than 20 speakers who participated in the ALS Canada Virtual Research Forum in August. You can listen to his full presentation online here.

Updated October 20, 2017

In the late 1980s, Dr. Neil Cashman was completing a neurology fellowship in ALS at the University of Chicago. At that time, little was known about the genetics or biology of ALS and Dr. Cashman became captivated by trying to understand the cause of the progressive paralysis he observed in his patients.

The Prion Hypothesis

Proteins, the substances responsible for almost all cellular functions, are molecules that consist of long chains of smaller units called amino acids. In order to complete its intended function within a cell, a protein must first fold into the appropriate 3D shape. If a protein misfolds, meaning it does not fold into the correct shape, the outcome can be toxic. A protein is said to have prion-like behaviour when it fulfills two major criteria: first, it must be able to cause other normally-folded proteins to change their shape and adopt a toxic shape. Second, it must trigger a chain reaction, moving from cell to cell creating a domino effect of toxic protein misfolding that spreads throughout the nervous system. Well-known prion diseases include scrapie in sheep, mad cow disease in cattle, and Creutzfeldt-Jakob disease in humans.

Targeting ALS

When Dr. Cashman read about the prion hypothesis, first published by Dr. Stan Prusiner in 1982, “it totally rang a bell that ALS could be a propagated protein misfolding disease,” he says. Now a professor in the Department of Neurology at the University of British Columbia and the Director of the Vancouver Coastal Health ALS Clinic, Dr. Cashman has been working on this theory ever since.

Early on, Dr. Cashman hypothesized that the misfolding of a protein called superoxide dismutase 1 (SOD1) may contribute to the breakdown of cells in the nervous system in ALS. Mutations in the SOD1 gene represent the second most common cause of the inherited (familial) form of ALS. Researchers still do not know the exact mechanisms by which mutations in SOD1 lead to the death of neuronal cells; however, studies suggest that misfolding may cause SOD1 to gain a toxic function.

Since mutations in SOD1 only account for approximately 2% of all ALS cases, Dr. Cashman wanted to find out if normal, non-mutated (wild-type) SOD1 could also adopt this abnormal and toxic shape. His theory was that if normal SOD1 could misfold, then SOD1 may also play a role in sporadic (non-familial) ALS, which represents more than 90% of all cases.

A breakthrough came when Dr. Cashman was able to show just that. “We found that mutant SOD1 is able to convert normal wild-type SOD1 to a disease-associated from that can transmit from cell to cell,” he describes.

Pushing the boundaries even further, Dr. Cashman later showed that when two additional prominent ALS proteins, TDP-43 and FUS, are mutated they are able to cause normal SOD1 to misfold in cells. Dr. Cashman explains that “this is very exciting in the context of sporadic ALS because TDP-43 abnormalities are present in approximately 98% of all ALS cases.”

Overall, Dr. Cashman’s work suggests that SOD1 may play a wider, more general role in ALS than previously thought to be the case. If prion-like induced misfolding of normal SOD1 does contribute to the breakdown of cells in the nervous system in ALS, then treatment strategies designed to block the domino-like misfolding should be successful at treating both the sporadic and familial forms of ALS. Dr. Cashman explains that “while we don’t have a definitive answer as of yet, we are continuing to work on this hypothesis.”

Progress in ALS research

Having been successful in attaining a number of grants through ALS Canada Research Program competitions, Dr. Cashman notes that “ALS Canada has stepped up to the plate in funding basic and translational ALS research in Canada, because of the donations of generous people” and speaks positively about the difference the country’s ALS research community is making on an international scale: “Canadians have always punched above their weight in ALS research, both in terms of publications and impact,” he says. “For reasons I’m not 100 per cent sure of, we seem to be a country in which great breakthroughs are being made and will continue to be made.”

Reflecting on his time 30 years ago at the ALS clinic at the University of Chicago, Dr. Cashman still remembers three young women who suffered from rapidly progressive ALS. With no information on the genes linked to ALS or the biology behind the mutations, Dr. Cashman remembers feeling “overwhelmed by the tragedy and deciding to make a vow to make some kind of contribution to ALS research.” Today, Dr. Cashman’s outlook on the state of the field has changed significantly. When asked his opinion on where ALS research is currently at, Dr. Cashman affirms that “there has never been a time in history where more people are working on ALS. I am not only hopeful, but truly optimistic, that soon there will be an effective treatment for ALS.”

ALS Canada Virtual Research Forum

Update: Dr. Cashman was one of more than 20 speakers who participated in the ALS Canada Virtual Research Forum in August. You can listen to his full presentation online here.

Updated October 20, 2017

Dr. Richard Bedlack’s passion for neurology started when he was a child. As many children do, he used to roll down hills with his little brother – but Dr. Bedlack’s inquisitive nature made him wonder why it made them dizzy. His fascination with the nervous system grew over time as he noticed some people walked differently or had shaking hands.

About twenty years ago, as a neurology resident at Duke University, he had a eureka moment when he met his first ALS patient. “It was the most dramatic physical exam I had ever seen. My attending doctor told me that we have no idea why ALS happens, we don’t know why people with it get worse, and we can’t do anything about it,” Dr. Bedlack said in an interview with ALS Canada. “I remember driving home that night, deciding that this would be the disease I would work on. There is such an unmet need. We should be offering people something to help make their lives better and have a research program to give them hope.”

Three years later, in 2001, he opened the Duke ALS Clinic in Durham, North Carolina, which has seen more than 2,000 unique patients and currently follows 400. “When we assess a person with ALS, we examine them from head to toe, for four to five hours, kind of like a NASCAR pit crew,” said Dr. Bedlack, director of the clinic, and an associate professor of medicine/neurology at Duke.

Dr. Bedlack’s can-do approach and attention to detail also fuel his research program. “We built Duke’s research program around the mindset that it’s not about what we can’t do, it’s focused on all the little things that we can do,” he said. His modesty is at odds with the significance of two programs he founded that benefit people living with ALS around the world: ALSUntangled and ALS Reversals.

ALSUntangled

Dr. Bedlack was surprised to discover that well over 50 per cent of people living with ALS were self-experimenting with alternative treatments they found on the Internet. Rather than adopting a “do this, don’t do that” approach, he created ALSUntangled to engage patients in shared decision-making about whether alternate treatments are worth trying.

The program has grown by leaps and bounds since it was launched in 2009. Through ALSUntangled’s website, people submit requests for a review of alternative or off-label treatments, adding a new item to the list or voting on items suggested by others. The ALSUntangled team conducts comprehensive reviews of the most-requested therapies using a scientific approach of gathering evidence and reporting results. They start by searching the scientific literature and news articles, then attempt to contact the source of the claims and see if they can perform a site visit to investigate. Finally, they poll the team of almost 100 clinicians volunteering with ALSUntangled to see if any of their patients have experience with the therapy.

Final reports are published in the journal Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. To date, ALSUntangled has completed over 40 reviews that are posted free online.

ALS Reversals

Dr. Bedlack’s work at ALSUntangled turned up a surprising new avenue of investigation — patients living with ALS whose conditions improved over time. “When I learned about the first patient with a real ALS reversal through ALSUntangled, I felt like Fox Mulder on the X-Files having an extraterrestrial moment,” said Dr. Bedlack. “That somebody with ALS could actually get better was a complete shock to me.”

Dr. Bedlack decided to establish the ALS Reversals program to better understand ALS reversals and to try and make them happen more often. To date, his team has confirmed 34 reversals since the program began in 2015.

One of the reversals is Mike McDuff, a resident of Providence, Rhode Island. McDuff had been diagnosed with ALS by multiple experts and had lost the ability to speak and swallow. Within six months of taking a supplement called lunasin, a soy product originally intended for lowering cholesterol, McDuff had improved so much that he was speaking normally in a television interview.

Dr. Bedlack decided to give McDuff’s lunasin regimen to 50 other patients to see if anyone else got better. This lunasin trial has taken three years to plan, coordinate and execute. The unique study design addresses some common frustrations with more typical ALS clinical studies. Since the objective is to look for a big response, the recruiting criteria are very broad. Patients measure their own ALSFRS scores and submit them by computer, and there are only three required on-site visits.

The study is no longer recruiting participants, but information about the study protocol and interim results are available at ALS Reversals and reports by participants can be viewed at PatientsLikeMe.

ALS Canada Virtual Research Forum

Update: Dr. Bedlack was one of more than 20 speakers who participated in the ALS Canada Virtual Research Forum in August. During his presentation, Dr. Bedlack provided an update on ALSUntangled, the latest results of the lunasin trial and the alternative therapies he’s considering studying next under the ALS Reversals program.

There are three things Dr. Bedlack hopes people will take away from his talk:

Dr. Bedlack’s presentation at the Virtual Research Forum is available online here.