Fast-Tracking Discovery in ALS Research: Collaboration, Innovation, and Open Science
- EverythingALS Editorial
- May 20
- 10 min read
Updated: May 21
Introduction:
Advancements in ALS research are increasingly driven by open science, cross-disciplinary collaboration, and patient-centered innovation. As the complexity of ALS demands multifaceted exploration—from genetic pathways to immune system dynamics—researchers, clinicians, and advocacy groups are collectively reshaping how discovery and development are approached. With an emphasis on early diagnostics, personalized treatment strategies, and real-world data collection, the landscape is evolving rapidly. This session with Dr. Merit Cudkowicz highlights emerging therapies, cutting-edge technologies, and the pressing need for inclusive, accessible clinical trials that accelerate progress and bring tangible hope to those impacted by ALS.
Featured Questions
What are your thoughts about the potential benefits of Spinogenix SPG 302? What stage is the trial at?
I like the biology and I put it in the repair category. It helps make new dendrites, so there are new connections between neurons. They are in early stages of study development and have completed a phase 2A study in Australia. They have not reported the results yet, but I believe the study had 24 participants for up to 6 months, with focus on identifying biomarkers. Furthermore, the study also analyzed the effectiveness and functional capacity of the drugs, e.g. increase of synapses, which can be measured through electrophysiology and other methods. Recently, they have announced a compassionate use study while they continue to work on the design of their phase 2B study.
What are your thoughts on IL-2 in MIRACALS ALS research study?
Firstly, it’s exciting their results were finally published. They had shared the results publicly, but it took them a long time to publish. I think it’s positive. The theory behind IL-2 is that it increases the good T-regulatory cells, which are anti-inflammatory in nature. The study reveals that from a subset of participants, the people who did not have super high neurofilament levels are people who are not super-fast progressors. This includes nearly 80% of the population which showed an effect on longevity. The reason why it didn’t work with people with a high neurofilament level is not very clear, but I do think they saw a fairly large subset that responded and showed that their drug increased T-regs so it did what its’s supposed to do. I didn’t know what the next step is because it’s a marketed drug for cancer, and, sometimes, it is possible to change the label of the drug based on new data. If you have a positive study, the FDA can review the data to determine whether there’s enough evidence to change the label and officially approve it as a marketed drug for ALS. Alternatively, the FDA or the other regulatory groups may want an additional study. In this case, the company provided the drug and it was an investigator-initiated study.
Will the Healey Center engage in NU9 clinical trials and are there any plans for it?
I think Akava would be a good example for an ALS research study, but they need to first do their Phase 1 study by testing their drug in people without any illness. For safety purposes, the study could administer either single dose or multi-dose. But, when they are ready for the next stage in people with ALS, the Healey centre Center would be perfect for the kind of a perfect setting for a Phase 2A study, to ensure the drug is administered to the target and right target population.
COYA is working to launch a Phase II trial this quarter for a combination of compounds. Does it include IL-2?
Yes. COYA includes IL-2 and another drug called Abatacept. So, it’s tackling two parts of the immune system that seem to be wrapped up in people with ALS. Dr. Appel has led major parts of the study and published on the first four patients, where he observed good safety and good response. And, now, they’re planning to launch an early Phase II trial, but the start date is not shared publicly.
What’s the difference between ALL ALS PREVENT and the Atlas Study?
The Atlas study is a therapeutic study in people who are gene carriers for SOD1, and will be administered the Qalsody drug to observe its mechanism, whether it can prevent the onset of illness. Whereas, ALL ALS PREVENT is following people with any gene that might cause ALS without any focus on the therapeutic intervention. It’s about following people with different outcome measures, whether they’re digital or fluid and try to understand the earliest changes that happen in ALS for not only improving the diagnosis, but also helping to design other prevention trials in those other forms of genetic ALS.
Are there any preliminary results for PrimeC Phase 3?
No, the Phase 3 trial for PrimeC hasn’t happened yet. So, PrimeC, developed by NeuroSense Therapeutics, is a combination of two drugs; Ciprofloxacin and Celecoxib. They have completed a Phase 2 study and reported positive biomarker data, safety, along and also with alpha measures, and they are gearing up for a Phase 3 trial.
Is there a known pathway by which COVID or COVID vaccinations could cause ALS?
There are some researchers working on this subject, especially Dr. Avi Nath at the National Institutes of Health (NIH). Although, a direct link has not been established, there is a compelling rationale for deeper study. One leading hypothesis suggests that viral infections may trigger inflammation or an immune response in individuals who are genetically predisposed to ALS or related conditions. Individuals who suspect a temporal link between their ALS onset and COVID infection or vaccination are encouraged to reach out to Dr. Nath, who is currently collecting blood samples for his research.
Do you have an opinion on the Phase 2 trial of ROCK (Rho-associated protein kinase) inhibitor Bravyl, and when the results of the study are anticipated?
I think it’s a good pathway, but I haven’t seen any results of it yet. But, I think it’s a good idea.
Any results from the Fasudil study?
I don’t think anything is published about the study yet.
What are your thoughts on the ALS research study at Sunnybrook involving the opening of the blood brain barriers to deliver medications?
This is conducted using focus ultrasound, where it is possible to briefly open up the blood brain barrier and release drugs in. This is a major problem for developing drugs for the brain. It could be very helpful for drugs to be administered once or twice. But, it may not work smoothly for drugs to be administered every day because it is not possible to get the focused ultrasound daily. But, for gene therapy, right now the drug could be injected in the spinal fluid or in the ventricles in the brain. The process is a little complicated, but if one could do it in the blood, and open up the blood brain barrier with the focus ultrasound for a couple of minutes, get in there, and then it shuts back down, it could be a game changer for gene therapy delivery for all forms of ALS.
As we study people with ALS, is research finding that most types of ALS have a genetic component?
I think it is. When I analyze the findings of Dr. Brown and Ammar Al-Chalabi, they talk about the twin studies where they have followed 25-30 pairs of identical twins to observe if they one or both twins develop ALS. They have concluded that about half of the cause of ALS is probably genetic. It’s not very simple with inheriting one gene from a parent that causes the illness. It’s probably complex genetics with multiple different gene changes that increase the risk. So, that’s the current number, with 50 % of the cause attributed to genetics, and the rest is attributed to environmental factors.
Any chance that the two-year mark to reject patients into trials will be removed at some point soon?
I don’t think so. I think we have to find other ways so that everybody has options. I think we are seeing more and more trials go earlier. For example, in the platform trial, we went earlier from 36 to 24. The reason is two-fold; one is some studies showing us better effects earlier, and if you take people who are up to 3 years, you are enriching for people who are slow progressors, which is great, we want everybody to be a slow progressor, but in a trial of 6 months or 9 months, it means someone might not change in that time period, and makes it much harder to conclude if the drug is functional or not. The goal of the trial is to confirm the drug’s efficacy with the fewest number of people so you can get it on the market for everybody. Also, the Prilenia trials are moving to to 18 months from symptom onset. So, I think there should be options for people who have passed the two-year or the 18 months mark. And that would be that compassionate use option, so that people can still have access to the drug and the therapy and be monitored safely. But, you are using the data from the people earlier in the illness to figure out if the drug works or not so then you can do a shorter trial to get that answer.
Can patients with Bulbar ALS also participate in the ALS research activities? What is the registration link?
Yes. All studies enroll people with bulbar ALS onset, whether that’s the ALL ALS, Natural History Database or the current clinical trials. I don’t have a specific link, other than finding the clinical trials at government website – clinicaltrials.gov. But, there’s also ALS TDI with a good website for clinical trial finding. You can also refer to the website of I AM ALS.
Why are the Canadian neurologists not prescribing Vitamin B12 – Methylcobalmin in the same way as it’s been given elsewhere?
While I can’t speak for the Canadians, but it’s approved in Japan. There were two studies – the first one was with a broad population, which did not see benefit, but they saw in a post-hoc analysis that there was a very big response if it was started early in the illness, between 12-15 months of first symptom. The second study was about adjusting people in the initial 12 months and observed a similar effect. These two studies have led to approval in Japan. However, it is not approved in Canada or in the US. This is not due to rejection by Health Canada or the FDA, but the company has not filed for approval. My guess is they are not prescribing it because it is not an approved drug.
What focus areas and orgs are doing the most exciting work leveraging AI for ALS research?
I think it’s going to be really helpful for the subgrouping of people for ALS research studies. I think we now have lot of data through Answer ALS and other groups on the biology from samples from people with ALS that we could start to subgroup people. There are some phenomenal scientists at UCSF, MIT, Hopkins and in our group who are real experts in AI trying to mine this data. I know Vision 2030 is very focused on AI and supporting that type of work with Everything ALS.
You mentioned PET scan to identify a neuroinflammatory process. Can this be indicated for a newly diagnosed ALS patient to indicate possible response to steroids?
Well, we can definitely do it in people who are newly diagnosed, and a lot of centers integrate a PET scan. It’s a protein called TSPO (18-kDa translocator protein). You could look at responses to steroids with it. There have been studies of steroids in people with ALS and they have not worked. So, I am not sure if it would be the best anti-inflammatory approach, but, other anti-inflammatory drugs could be used and PET scan to observe if the neuroinflammation decreases.
What are your thoughts on testosterone, and the role that it plays in ALS onset in men? Do you think there is a connection and if so, would that impact the ALS treatment options?
I don’t think there is adequate research about the connectivity. However, with respect to clinical understanding, if the testosterone is low, it should definitely be replaced. I don’t think we should give it if testosterone levels are normal, but if it is low, we should give it a try. However, there should be more research studies about it.
Are there any recent results from Ibudilast study? The previous results in 2020 were negative.
Not yet. I think it was supposed to finish in April. I don’t know if they have actually finished enrolling and then it will be about a year from when the last person enrolled. So, I don’t think we are going to know for a while. The previous study on a small scale was open label and it was looking at the PET scan. We were looking at those measures of inflammation and we did not see any change in inflammation or in neurofilament. It was a small study, with 35 participants over a six-month period. The current study is much bigger, and they are looking at different outcome measures, but I don’t think we’ll know the results until 2026, unfortunately.
How soon will treatments have FDA approval, based on all the information discussed and the current pipeline?
I hope there will be some approvals in 2026. The approval process and the timeline are only known to the FDA. I hope we are going to have the flexibility that we had with the prior administration. Presently, they are very short-staffed and things are taking longer to get back from them, but hopefully, that will settle out. So, I think it is less likely to have something new this year. I think if Eisai filed for Vitamin B12, it might get approved quickly, but I don’t know that for a fact.
Do you have ALS patients with neurofilament levels that remain normal throughout their disease?
Yes. It tends to be in people who have a very slow or isolated form of ALS. For example, for some people, only the arm or leg area is impacted and progression is very slow. It might be that the damage is so minor that it does not leak into the blood, but we definitely see it. I take it as a good sign when people have that.
Conclusion:
The path to meaningful breakthroughs in ALS research is rooted in open collaboration, scientific rigor, and a commitment to patient equity. By leveraging new biomarkers, repurposing existing drugs, integrating AI, and investing in preventative frameworks, the research community is making strides toward transforming how ALS is understood and treated. Continued support for open science initiatives, compassionate trial designs, and real-time data sharing will be essential in ensuring that discovery is not just fast-tracked, but also impactful and inclusive. Together, these efforts are paving the way for a more hopeful and effective future in ALS care. For any other questions on ALS research, you can download the Everything ALS app on Google Play Store or Apple App Store and learn more from our Chatbot.
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