When I was diagnosed with ALS, I thought there would be several companies and research facilities who would contact me and ask if they could include me in studies and research to assist in the discovery of treatments and eventually a cure. I anticipated becoming a lab rat that got poked and prodded regularly. Not only has that not happened, but I am officially excluded as a potential participant in nearly every trial that I’ve researched. A common requirement for being included in clinical trials is to be within two years of the initial onset or recognition of the symptoms of ALS. In my case it took almost 2 1/2 years to get to even a firm diagnosis so I was already out of the clinical trial window from the beginning. This is significantly frustrating for me because I feel like I am progressing relatively slowly compared to other people that have ALS. I often find out about new drugs and processes that are being tested in clinical trials and when I look up the requirements it’s always two years or less living with the disease. With that said, below are a few clinical trials and drugs in testing for ALS. I cheated a little bit and had ChatGPT helped me write part of the article below.
As of 2025, the landscape of clinical trials for amyotrophic lateral sclerosis (ALS) is marked by significant advancements, promising therapies, and a renewed sense of urgency in the scientific community. With over 100 active trials worldwide, researchers are exploring a diverse array of treatment modalities, from gene therapies and antisense oligonucleotides to immune modulators and neuroprotective agents. This article delves into the current status of ALS clinical trials, highlighting key developments, ongoing studies, and the challenges that persist in the quest for effective treatments.
BREAKTHROUGHS IN GENETIC-BASED THERAPIES
NurOwn
NurOwn® is an investigational stem cell-based therapy developed by BrainStorm Cell Therapeutics for the treatment of amyotrophic lateral sclerosis (ALS). The therapy utilizes autologous mesenchymal stem cells (MSCs) derived from a patient’s bone marrow, which are cultured and induced to secrete neurotrophic factors—proteins that support neuron survival and function. These MSC-NTF cells are then administered via intrathecal injection into the patient’s spinal fluid. The approach aims to address key pathological processes in ALS, including neuroinflammation, neurodegeneration, and impaired neuroprotection. Early clinical trials showed promise, particularly in patients with less advanced disease, where the therapy demonstrated potential to slow disease progression and reduce biomarkers associated with neurodegeneration.
Building upon these findings, BrainStorm is advancing a Phase 3b clinical trial, designated BCT-006-US, to further evaluate NurOwn’s efficacy and safety in patients with early-stage ALS. This multicenter, two-part study is designed to enroll approximately 200 participants who have experienced symptom onset within the past two years. In the first part of the trial, participants will receive three doses of NurOwn or a placebo over 24 weeks, followed by a 24-week open-label extension during which all participants will receive NurOwn. The primary endpoint is the change in the Revised ALS Functional Rating Scale (ALSFRS-R) from baseline to week 24, with secondary endpoints including survival analysis and biomarker assessments. The trial has received a Special Protocol Assessment (SPA) from the U.S. Food and Drug Administration (FDA), indicating alignment on the study’s design and endpoints to support a future Biologics License Application (BLA).
QALSODY® (Tofersen): A Milestone in Targeted Treatment
Tofersen, marketed as QALSODY®, represents a landmark achievement in ALS therapy. This antisense oligonucleotide targets the SOD1 gene mutation, a known cause of familial ALS. Approved by the FDA in April 2023, QALSODY has shown promise in halting disease progression in patients with this specific genetic mutation. Patients have reported significant improvements, with some experiencing stabilization of symptoms and enhanced quality of life. However, challenges remain regarding its accessibility and the need for early genetic diagnosis to identify suitable candidates.
AMX0114: Targeting Calpain-2 for ALS Treatment
Amylyx Pharmaceuticals is advancing AMX0114, an antisense oligonucleotide aimed at inhibiting calpain-2, a protein implicated in neuronal degeneration. Following the lifting of a clinical hold by the FDA in January 2025, the Phase 1 LUMINA trial is set to commence in North America. This multicenter, randomized, placebo-controlled study will assess the safety, tolerability, and pharmacodynamics of AMX0114, including its effects on neurofilament light (NfL) levels, a biomarker associated with ALS progression.
IMMUNE MODULATION AND NEUROPROTECTION
CNM-Au8: Investigating Neuroprotective Potential
Clene Inc.’s CNM-Au8 is an investigational nanocatalytic therapy designed to reduce oxidative stress and promote neuronal survival. The Phase 2 RESCUE-ALS trial and its open-label extension have suggested a potential survival benefit for patients receiving prolonged treatment. Building on these findings, the Phase 3 RESTORE-ALS trial is scheduled to begin in 2025, aiming to confirm these results and assess the drug’s efficacy in slowing disease progression. The company also plans to submit an application for accelerated FDA approval based on NfL biomarker data.
Fosigotifator: Modulating the Integrated Stress Response
AbbVie and Calico Life Sciences are developing fosigotifator (ABBV-CLS-7262), a small-molecule prodrug that modulates the integrated stress response pathway. This approach aims to enhance cellular resilience and protect against neurodegeneration. Early-phase studies are underway to evaluate the safety and tolerability of fosigotifator in ALS patients, with plans for further clinical trials to assess its therapeutic potential.
ADVANCEMENTS IN GENETIC RESEARCH AND THERAPY
Expanding Genetic Understanding of ALS
The field of ALS genetics has seen rapid progress, with the identification of two to three new causative genes annually. This expansion is facilitated by large-scale genome sequencing efforts, including those focusing on underrepresented populations. These discoveries are crucial for developing targeted therapies and understanding the diverse genetic underpinnings of ALS.
Emerging Gene Editing Technologies
Innovations in gene editing, such as CRISPR-Cas9 and base editing, hold promise for correcting genetic mutations at the DNA level. These technologies are being explored in preclinical models of ALS, with the potential to offer curative treatments for genetic forms of the disease. However, challenges related to delivery mechanisms, off-target effects, and ethical considerations remain to be addressed.
CHALLENGES IN ALS CLINICAL TRIALS
Recruitment and Retention
Recruiting and retaining participants for ALS clinical trials is a significant challenge due to the disease’s rapid progression and the need for early intervention. Strategies to address these issues include expanding trial sites, utilizing telemedicine for remote monitoring, and simplifying inclusion criteria to accommodate a broader patient population.
Biomarker Development
Reliable biomarkers are essential for assessing treatment efficacy and disease progression in ALS. While NfL has emerged as a promising biomarker, its role as a surrogate endpoint for regulatory approval is still under investigation. The FDA has indicated that additional biomarker data, including analyses from compassionate use programs, will be necessary to support the accelerated approval of therapies like CNM-Au8.
Regulatory Hurdles
The regulatory pathway for ALS therapies is complex, with the FDA requiring robust evidence of clinical benefit before granting approval. While accelerated approval mechanisms exist, they necessitate the submission of additional data, such as biomarker analyses and survival modeling, to confirm the long-term benefits of treatments.
GLOBAL COLLABORATIONS AND EXPANDING ACCESS
International partnerships are playing a pivotal role in advancing ALS research. For instance, Texas A&M University’s collaboration with Saudi Arabia’s King Faisal Specialist Hospital & Research Centre aims to conduct clinical trials for ALS therapies utilizing T-regulatory cells derived from umbilical cord blood. This approach seeks to address inflammation and promote neuroprotection, with early studies showing promise in stabilizing disease progression.
Such collaborations not only enhance the diversity of clinical trial populations but also facilitate the sharing of resources and expertise, accelerating the development of effective ALS treatments.
