When Will There Be a Cure for Lou Gehrig’s Disease?
American sports just aren’t what they used to be. The stink of politics seems to be permeating nearly every sport, and the athletes hardly seem to be people our youth should be looking up to. Take the National Football League (NFL) for example. USA Today put together a database to track arrests of NFL players, and the number is now at 927 arrests since 2000. We’re already off to a good start in 2019 with five arrests recorded so far.
It makes you yearn for the days when sports players were known for contributing to society in a positive manner as much as their sporting prowess. Take Yogi Berra for example, a man known for his witty sayings or “berra-isms” such as telling people to “always go to other people’s funerals, otherwise they won’t come to yours.” Then there was Babe Ruth, a man whose worst offenses included drinking too much and womanizing, while his better attributes were to do good by visiting children at hospitals and orphanages. And there was Lou Gehrig, a class act who was one of the greatest baseball players ever, but who is perhaps best known today for the disease that bears his name.
What is Lou Gehrig’s Disease?
Amyotrophic Lateral Sclerosis (ALS), or what’s most often referred to as Lou Gehrig’s disease, is a neurodegenerative disease that affects nerve cells in the brain and the spinal cord, progressively getting worse over time. It’s a relatively rare disease only affecting around 20,000 Americans yearly but is notable for the fact that it has no known cure. Worse than that, there is “no effective treatment to halt, or reverse, the progression of the disease.” That’s according to an article by the NIH Neurological Institute which tells us the disease mainly affects the nerve cells (neurons) responsible for controlling voluntary muscle movements like chewing, walking, and talking. The article goes on to say:
Early symptoms of ALS usually include muscle weakness or stiffness. Gradually all muscles under voluntary control are affected, and individuals lose their strength and the ability to speak, eat, move, and even breathe.
Symptoms of ALS commonly develop between the ages of 55 and 75, in most cases for no discernible reason at all. This unfortunate fact is why the second most common search for Lou Gehrig’s disease is “Lou Gehrig’s disease cause” which implies that the poor people who have contracted the disease want to know “why me?”
Who Gets Lou Gehrig’s Disease?
Maybe the most well-known person to have Lou Gehrig’s disease was Stephen Hawking, a man who suffered from a “slow-progressing” form of ALS that slowly paralyzed him over the 76 years he managed to remain on this earth. Ninety percent of ALS cases are sporadic in that there is no reason for the onset of the disease which seems to occur purely at random. However, the prevalence of Lou Gehrig’s disease is not evenly distributed across populations which is quite puzzling considering it’s supposed to occur at random. Some studies have suggested that military veterans are more likely to get the disease for reasons that are unclear (it’s recognized as a service-connected disease by the U.S. Department of Veterans Affairs). It’s also more prevalent among Caucasians and Hispanics with 5 to 10 percent of all cases inherited from parents. Regardless of what causes the disease, most people with ALS will die from respiratory failure within 3 to 5 years from when the first symptoms appear.
A Cure for Lou Gehrig’s Disease
As with any disease that suddenly afflicts people with no warning, the desire to find a cure and exercise some control over the situation is strong. The fact that there is no known cure and no way to halt the progression of the disease just makes things even worse. Given how few people are affected by the disease as a percentage of the population, you wouldn’t expect drug companies to be focusing much on looking for a cure. However, that’s not the case, and it turns out there are a meaningful number of companies working on ALS-related therapies. That could be partially explained by the fact that there are only a few FDA approved treatments for ALS today.
- Edaravone (Radicava, Radicut) – demonstrated to slow decline of physical function in ALS patients by 33 percent. The FDA approved Radicava in 2017 less than a year after Mitsubishi Tanabe Pharma Corporation submitted a New Drug Application. It was the first new treatment specifically for ALS in 22 years and only the second drug ever approved to treat A.L.S.
- Riluzole (Rilutek, Teglutek) – The first drug for ALS approved by the FDA in 1995 may increase survival by approximately two to three months
Not knowing exactly what causes the disease makes it awful hard to find a cure for it. What we can hope to do is increase life expectancy to such an extent that people with Lou Gehrig’s disease die from old age instead. Let’s look at some companies working on better treatments.
Some Startups Working on ALS
Founded in 2009, Danish startup Orphazyme has taken in nearly $59 million in funding to develop their experimental drug, arimoclomol, for a number of indications including ALS. In August of last year, they initiated a Phase III trial “to support the application for a marketing authorization in ALS” which was agreed upon with the regulatory authorities to involve an 18-month, placebo-controlled trial including 212 patients. They expect interim analysis at 70% completion in the second half of 2020 and full analysis in the first half of 2021.
Founded in 2000, Seattle area startup Revalesio has taken in just over $38 million to develop therapeutics for the treatment of inflammatory diseases. One of the products they are developing is an investigational drug treatment for ALS called RNS60 which was granted fast track status by the FDA earlier just last month. A result of one study published late last year showed promising results with the news release quoting the company’s president as making the following statement:
“In people with ALS, vital capacity usually drops by about 3 percentage points every month”, said Archambeau. “In contrast, we saw roughly the same drop over 5 months of treatment in the study at MGH.”
Back of the napkin math would tell us that this treatment has the potential to slow the progression of ALS enough to extend life expectancy by five times.
Founded in 2013, Amylyx Pharmaceuticals has taken in $9.4 million in funding to develop the company’s lead therapeutic, AMX0035, which is “designed to simultaneously target pathways originating in the mitochondria and endoplasmic reticulum which lead to neuronal death and degradation.” The drug was granted Orphan Drug Designation by the FDA and is currently in clinical trials in both Alzheimer’s disease and ALS. The Phase 2 clinical study for ALS is scheduled to be completed by the end of this year.
Update 07/01/2020: Amylyx Pharmaceuticals has raised an additional $30 million in funding. This brings the company’s total funding to $67.2 million to date.
Founded just last year, QurAlis is a Boston startup specifically focused on discovering and developing new therapies for ALS. Founded by Harvard professors and ALS and stem cell pioneers, the startup has taken in $5.5 million from investors that include Mitsubishi Tanabe Pharma Corporation (the company behind the most recently FDA approved ALS treatment, Radicava) as well as Amgen (AMGN). QurAlis is developing three precision therapies targeting three distinct subtypes of ALS:
- A drug to restore a dysfunctional cellular waste clearance system that progressively poisons neurons;
- A drug to treat overactive neurons and prevent cell death via excitotoxicity;
- A drug to stop nerve loss in a large portion of sporadic ALS patients
The company’s strategy is to develop targeted therapies for specific ALS patients identified by genetics and biomarkers, for which the cause of the disease is well understood. Success with any of these therapies will have a tremendous positive impact on ALS patients and their families.
Some Publicly Traded Companies
Late last year, the $64 billion pharmaceutical giant Biogen (BIIB) and a much smaller $8 billion firm called Ionis Pharmaceuticals (IONS) announced that Biogen obtained from Ionis “a worldwide, exclusive, royalty-bearing license to develop and commercialize BIIB067 (IONIS-SOD1RX), an investigational treatment for ALS with superoxide dismutase 1 (SOD1) mutations.” The press release goes on to say that “ALS with SOD1 mutations is a subtype of familial ALS and accounts for approximately two percent of all ALS cases.” Seems like a rather small population to be targeting, but this could lead to something bigger. According to Biogen, “mutations within multiple genes are believed to cause ALS, including mutations in the SOD1 gene.”
An $83 million firm called Brainstorm Cell Therapeutics (BCLI) has built a platform called NurOwn which takes stem cells from patients and then grows and manipulates them such that they can then be used to “treat highly debilitating neurodegenerative diseases that currently have limited treatment options.” They’re currently in Phase 3 clinical trials and are looking to enroll ALS 200 patients with expectations to wrap up the whole thing by the middle of this year. At the same time, they’re also in Phase 2 trials for treating progressive multiple sclerosis using the same platform.
Can AI Cure Lou Gehrig’s Disease?
There are quite a few companies out there using artificial intelligence to find drug candidates, one being a British unicorn called BenevolentAI. In 2016, the startup did something quite remarkable. Despite having no technological or scientific expertise in ALS, it took just half a day for their algorithms to find a list of potential hypotheses for the treatment of ALS. They then worked on condensing the list, and in their own words:
After a week, we had arrived at five hypotheses that represented the best potential treatments for the disease. We took these initial hypotheses to the world authority on ALS – the Sheffield Institute for Translational Neuroscience (SITraN). They were astonished by what we had done. One of our hypotheses matched their ongoing research and two were completely novel. After a year of further study and testing, it was announced that our technology may have found a way to prevent the death of motor neurones, a key to finding a cure for this disease – an important inventive step.
We’ve listed just a few of the companies that are working on new therapies for ALS, and this is hardly an exhaustive list (ALS News Today seems to be a pretty good source of information on new treatments). A quick search through Crunchbase shows quite a few companies out there focusing on neurodegenerative diseases as a whole, ALS being one of them. A common theme with these treatments is that they all seek to slow progression. Until we can halt progression, or even reverse progression, we won’t have a “cure” for Lou Gehrig’s disease.
Seems like it was just yesterday when all the lemmings were dumping buckets of ice water over their heads, pretending to raise awareness for Lou Gehrig’s disease, when most were just looking for the next dumb thing to post on social media. Since then, some of the therapies being worked on have failed, like one from Cytokinetics called Tirasemtiv, which was their lead drug candidate – having received fast track designation back in 2012 – making it all the way to Phase 3 trials. Another company, AB Science, also saw their drug Masitinib rejected by the European Medicines Agency as a potential ALS treatment last year. Yet another, an investigational therapy called NP001 from Neuraltus, was in a Phase 2 study that failed to meet its endpoints. Still, many companies continue to try, and in the words of Yogi Berra, “it ain’t over til it’s over.”
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