Amyotrophic lateral sclerosis (ALS) is a complex and challenging disease, impacting motor neurons and leading to progressive weakness. While there is currently no cure, the landscape of ALS research is rapidly evolving. Clinical trials are at the heart of this progress, offering hope and testing potential new therapies that could slow, stop, or even reverse the effects of ALS.

For patients, caregivers, and families, participating in ALS clinical trials can feel like a significant step. It's an opportunity to potentially access cutting-edge treatments and, crucially, to contribute vital information that helps the entire ALS community. Understanding what clinical trials are, why they are important, and how to get involved is key.

Why are ALS Clinical Trials So Important?

Clinical trials are research studies involving people that are designed to test new treatments, interventions, or ways to diagnose and manage a disease. For ALS, trials are essential for several reasons:

Testing New Therapies: They evaluate the safety and effectiveness of potential new drugs, gene therapies, cell-based treatments, or other interventions.
Advancing Understanding: They provide researchers with critical data on how ALS progresses and how potential therapies interact with the disease.
Leading to Approved Treatments: Successful clinical trials can lead to new therapies being approved by regulatory bodies, making them available to a wider patient population.

Significant discoveries have been made in understanding ALS genetics, pathology, and biomarkers over the past decade and a half, laying the groundwork for identifying targeted therapies with diverse mechanisms of action, as noted by Mead and colleagues in 2023. This advanced knowledge is being applied in clinical trials to translate findings from preclinical studies into potential benefits for patients.

What Kinds of Therapies are Being Studied?

The ALS clinical trial landscape is expanding, exploring a variety of approaches to tackle this complex disease. According to supporting information, novel strategies are targeting underlying issues like oxidative stress (cellular damage), neuroinflammation (inflammation in the nervous system), and mitochondrial dysfunction (problems with energy production in cells).

Research is also heavily focused on genetic factors and the mechanisms driving motor neuron degeneration. Some promising areas include:

Targeting Specific Genes: Given that genetic mutations account for a significant portion of ALS cases (both familial and sporadic), strategies to silence or correct faulty genes are being explored. This includes approaches like:
- Antisense Oligonucleotides (ASOs): These molecules can interfere with the production of harmful proteins from specific genes, such as SOD1 or C9orf72 mutations, which are common genetic causes of ALS. Van Daele and colleagues in 2024 highlighted ASOs as entering a "new era" for ALS treatment, showing promise particularly for familial forms but also being explored for sporadic cases. Abati and co-authors reviewed the potential of SOD1 silencing as a therapeutic target in 2020.
- Gene Therapy: Broader gene therapy approaches, including using viruses to deliver therapeutic genes (AAV-mediated trophic support), RNA interference (RNAi), and potentially even gene editing techniques like CRISPR, are under investigation to address both specific genetic mutations and sporadic ALS, as discussed by Amado and Davidson in 2021.
Modulating the Immune System: Immune dysregulation and neuroinflammation are recognized features of ALS. Beers and Appel (2019) discussed how understanding these processes is leading to potential therapeutic strategies, including emerging cell-based therapies.
Other Novel Drugs: Studies are testing drugs identified through various discovery methods, such as the Phase 1/2a trial of ropinirole, a drug candidate found using iPSC-based drug discovery, as reported by Morimoto and colleagues in 2023.
Non-Pharmacological Interventions: While the focus of drug trials is on disease modification, other studies explore interventions like therapeutic physical exercise or respiratory muscle training to manage symptoms and potentially slow functional decline, as reviewed by Ortega-Hombrados et al. (2021) and Silva et al. (2019).

Innovations in trial design are also helping researchers better select patients and potentially improve the ability to detect clinical benefits, according to supporting information.

Who Can Participate in a Clinical Trial?

Clinical trials have specific criteria that participants must meet to ensure the study is conducted safely and effectively, and to allow researchers to accurately assess the treatment being tested. These criteria often include:

Diagnosis: Confirmation of an ALS diagnosis.
Disease Stage/Progression: Trials may recruit patients at specific stages of their disease or with a certain rate of progression, often measured using scales like the ALSFRS-R (Revised Amyotrophic Lclerosis Functional Rating Scale), which assesses functional status.
Genetic Profile: Some trials are specifically for patients with certain genetic mutations (e.g., SOD1, C9orf72), while others include sporadic (non-familial) ALS.
Other Health Conditions: Certain co-existing medical conditions might exclude participation for safety reasons.
Location and Mobility: Ability to travel to the study site for regular visits.

It's important to note that even related conditions, like Progressive Muscular Atrophy (PMA) with only lower motor neuron signs, might not meet the criteria for standard ALS clinical trials, as highlighted by Liewluck and Saperstein (2015). Eligibility is always determined on a case-by-case basis by the study team based on the specific trial's protocol.

How Can You Find and Join an ALS Clinical Trial?

Finding the right clinical trial requires active searching and discussion with your healthcare team. Here are common steps:

Talk to Your Neurologist/ALS Specialist: Your doctor is the best resource. They are familiar with your medical history and disease progression and may know about trials recruiting in your area or nationally that could be a good fit.
Search Online Databases:
- ClinicalTrials.gov: This is a registry of clinical trials worldwide. You can search by condition (Amyotrophic Lateral Sclerosis or ALS), location, and keywords (like "new therapy," "gene therapy"). Each listing provides details about the trial, including its purpose, eligibility criteria, locations, and contact information.
- Patient Advocacy Group Websites: Organizations like the ALS Association, Muscular Dystrophy Association (MDA), and I AM ALS often have resources, databases, or navigators to help you find trials.
Contact Trial Sites Directly: Once you find a promising trial listing online, you can contact the listed research site or coordinator to learn more and inquire about eligibility.
Consider ALS Registries: While not clinical trials themselves, participating in patient registries helps researchers understand disease patterns, identify potential participants for future studies, and track outcomes. Longinetti and Fang (2019) emphasized the importance of population-based registries in ALS research.

What to Consider Before Participating?

Deciding whether to join a clinical trial is a very personal choice. It's crucial to weigh the potential benefits and risks and discuss them thoroughly with your family, caregivers, and healthcare team.

Potential Benefits:

Access to potential new treatments before they are widely available.
Contributing to scientific knowledge that could help others with ALS in the future.
Receiving close medical attention from a research team experienced in ALS.

Potential Risks:

The treatment may not be effective or may not work better than existing options.
There may be side effects, some of which could be serious or unexpected.
You might be assigned to a placebo group (receiving an inactive substance) depending on the trial design.
Participation often requires frequent visits, tests, and procedures, which can be time-consuming and require travel.
The trial might be stopped early (as was the case for the bimagrumab trial in sIBM, discussed by Amato and others in 2021, though this was not an ALS trial, it illustrates that trials can stop).

Before joining any trial, you will go through an informed consent process. The research team will explain the study's purpose, procedures, risks, benefits, and your rights as a participant. You should ask questions until you feel comfortable and fully understand what is involved. Participation is always voluntary, and you have the right to leave a trial at any time.

The Clinical Trial Process

Clinical trials typically proceed through different phases:

Phase 1: Tests a new treatment in a small group of people (20-80) to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: Evaluates the treatment in a larger group (100-300) to further assess its safety and effectiveness.
Phase 3: Studies the treatment in large groups (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to standard treatments, and collect information that will allow the treatment to be used safely.
Phase 4: Post-marketing studies conducted after a treatment is approved and on the market to gather additional information on the treatment's risks, benefits, and optimal use.

Most patients considering new therapies will be looking at Phase 2 or Phase 3 trials.

Your Role in Progress

Participating in an ALS clinical trial is a significant commitment, but it is also a powerful way to contribute to the fight against this disease. Every participant provides invaluable data that moves research forward. Whether through testing a novel gene therapy, evaluating a drug targeting neuroinflammation, or participating in a registry, individuals affected by ALS play a crucial role in the collective effort to find effective treatments and ultimately a cure.

If you are considering joining a trial, start by having an open conversation with your medical team. They can help you understand if a trial might be right for you and guide you through the process of finding potential opportunities.

References

Abati, E., Bresolin, N., Comi, G., & Corti, S. (2020). Silence superoxide dismutase 1 (SOD1): a promising therapeutic target for amyotrophic lateral sclerosis (ALS). Expert Opinion on Therapeutic Targets, 24(10), 1013–1027.

Al-Chalabi, A., & Hardiman, O. (2013). The epidemiology of ALS: a conspiracy of genes, environment and time. Nature Reviews Neurology, 9(11), 617–628.

Amado, D. A., & Davidson, B. L. (2021). Gene therapy for ALS: A review. Molecular Therapy, 29(11), 3140–3156.

Beers, D. R., & Appel, S. H. (2019). Immune dysregulation in amyotrophic lateral sclerosis: mechanisms and emerging therapies. The Lancet Neurology, 18(2), 211–220.

Goutman, S. A., Savelieff, M. G., Jang, D.-G., Hur, J., & Feldman, E. L. (2023). The amyotrophic lateral sclerosis exposome: recent advances and future directions. Nature Reviews Neurology, 19(10), 611–626.

Kiernan, M. C., Vucic, S., Cheah, B. C., Turner, M. R., Eisen, A., Hardiman, O., Burrell, J. R., & Zoing, M. C. (2011). Amyotrophic lateral sclerosis. The Lancet, 377(9769), 942–955.

Kim, G., Gautier, O., Tassoni-Tsuchida, E., Ma, X. R., & Gitler, A. D. (2020). ALS Genetics: Gains, Losses, and Implications for Future Therapies. Neuron, 108(2), 242–262.

Liewluck, T., & Saperstein, D. S. (2015). Progressive Muscular Atrophy. Continuum: Lifelong Learning in Neurology, 21(5), 1507–1518.

Longinetti, E., & Fang, F. (2019). Epidemiology of amyotrophic lateral sclerosis: an update of recent literature. Current Opinion in Neurology, 32(5), 771–776.

Mead, R. J., Shan, N., Reiser, H. J., Marshall, F., & Shaw, P. J. (2023). Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation. Nature Reviews Drug Discovery, 22(12), 987–1011.

Morimoto, S., Takahashi, S., Ito, D., Daté, Y., Okada, K., Kato, C., Nakamura, S., Ozawa, F., Chyi, C. M., Nishiyama, A., Suzuki, N., Fujimori, K., Kondo, T., Takao, M., Hirai, M., Kabe, Y., Suematsu, M., Jinzaki, M., Aoki, M., ... Nakahara, J. (2023). Phase 1/2a clinical trial in ALS with ropinirole, a drug candidate identified by iPSC drug discovery. Stem Cell Reports, 18(10), 2081–2098.

Ortega-Hombrados, L., Molina-Torres, G., Galán-Mercant, A., Sánchez-Guerrero, E., González-Sánchez, M., & Ruiz-Muñoz, M. (2021). Systematic Review of Therapeutic Physical Exercise in Patients with Amyotrophic Lateral Sclerosis over Time. Journal of Clinical Medicine, 10(23), 5626.

Silva, I. S., Pedrosa, R., Azevedo, I. G., Forbes, A.-M., Fregonezi, G. A., Dourado Junior, M. E. T., Lima, S. R. H., & Ferreira, G. M. H. (2019). Respiratory muscle training in children and adults with neuromuscular disease. Cochrane Database of Systematic Reviews, (12), CD011764.

Van Daele, S. H., Masrori, P., Van Damme, P., & Van Den Bosch, L. (2024). The sense of antisense therapies in ALS. Nature Reviews Neurology, 20(3), 141–154.

Your Role in Progress: Joining ALS Clinical Trials