Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that damages motor neurons in the brain and spinal cord. Motor neurons carry signals that allow voluntary muscles to move. As these nerve cells become damaged and die, the brain gradually loses its ability to control muscles used for walking, speaking, swallowing, and breathing. Symptoms and the rate of progression vary from person to person.

Common Symptoms

ALS is primarily a motor-neuron disease, but it does not always leave thinking and behavior unaffected. Some people develop cognitive or behavioral changes, and a smaller proportion develop frontotemporal dementia (FTD). These differences can affect communication, decision-making, and care planning.

There is currently no cure for ALS. Established care focuses on slowing disease progression when possible, treating symptoms, maintaining independence and communication, supporting breathing and nutrition, and preserving quality of life.

Standard Treatment Categories

• Riluzole: An FDA-approved medication used to slow ALS progression and extend survival in some patients.
• Edaravone: Available in intravenous and oral formulations and approved for the treatment of ALS.
• Tofersen: An antisense oligonucleotide approved for people with ALS associated with a mutation in the SOD1 gene.
• Respiratory care: Noninvasive ventilation, cough-assist strategies, and other respiratory support may be introduced as breathing muscles weaken.
• Nutrition and swallowing support: Dietitians, speech-language pathologists, modified food textures, and feeding-tube support may help maintain nutrition and reduce aspiration risk.
• Physical, occupational, and speech therapy: Rehabilitation and assistive technology can help preserve mobility, independence, communication, and safety.
• Multidisciplinary ALS care: Coordinated care from neurology, respiratory therapy, rehabilitation, nutrition, speech-language pathology, nursing, social work, and other specialties can address the complex needs of people living with ALS.

ALS treatment is individualized. Genetic testing may also influence treatment decisions because some therapies, including tofersen, are designed for specific genetic forms of the disease.

Regenerative medicine research in ALS is exploring several types of cell-based and biologic approaches. These include mesenchymal stromal cells (MSCs), neural stem or progenitor cells, engineered cells that release neurotrophic factors, and immune-cell therapies such as regulatory T cells. These approaches are not interchangeable. They use different cell types, delivery methods, biologic mechanisms, doses, and treatment schedules, and findings from one product or trial should not be assumed to apply to another.

What Researchers Are Studying

• Whether cell-based approaches can be delivered safely to people with ALS
• Whether specific cells or cell-derived signals can support motor-neuron survival
• How neuroinflammation and immune activity may influence ALS progression
• Whether cells can deliver growth or neurotrophic factors to vulnerable areas of the nervous system
• Changes in ALS Functional Rating Scale-Revised (ALSFRS-R) scores, survival, respiratory measures, and biomarkers
• Which cell sources, doses, delivery routes, and treatment schedules warrant larger controlled trials

Note: Stem cell, mesenchymal stromal cell, exosome, and other regenerative medicine therapies are not FDA-approved for ALS. The FDA specifically identifies ALS among neurological conditions for which regenerative medicine products have not been approved.

How Cell-Based Therapy for ALS Is Being Studied

Clinical research has used several delivery approaches, including intravenous infusion, intrathecal administration into the cerebrospinal fluid, and direct transplantation into the spinal cord. Researchers have also studied cells engineered to release neuroprotective proteins and regulatory immune cells intended to influence inflammatory activity. Most studies to date have been early-phase trials designed primarily to evaluate safety, feasibility, dosing, and biologic activity. Some have reported favorable changes in functional decline, survival, biomarkers, or selected clinical measures, but the studies differ substantially in design and many include small numbers of participants. For this reason, cell-based treatment for ALS should be considered product-specific, protocol-specific, and investigational.

2025: Umbilical Cord Blood-Derived Regulatory T-Cell Therapy Showed Preliminary Safety

Clinical Safety and Preliminary Efficacy of Regulatory T Cells for ALS — Read Study

This early clinical study evaluated CK0803, an off-the-shelf regulatory T-cell product derived from umbilical cord blood. Six people with ALS received repeated intravenous infusions, with a median of 11 infusions per participant. No dose-limiting toxicity was observed. Among the four participants with sufficient functional data for the exploratory analysis, the mean ALSFRS-R rate of decline changed from 1.66 points per month before treatment to 0.41 points per month during treatment. Because this was a very small safety study without a concurrent control group, the results cannot establish effectiveness, though the findings provide encouraging early support for continued randomized study.

2023: Repeated Intravenous Muse-Cell Treatment Demonstrated Favorable Tolerability

Safety and Clinical Effects of a Muse Cell-Based Product in Patients With Amyotrophic Lateral Sclerosis: Results of a Phase 2 Clinical Trial — Read Study

Five people with ALS received six monthly intravenous doses of CL2020, an allogeneic Muse-cell product. The primary endpoints were safety and tolerability, with ALSFRS-R change evaluated as a secondary outcome. The treatment was well tolerated without serious treatment-related side effects. Three of the five participants showed a decrease in the rate of ALSFRS-R decline, though the overall functional change was not statistically significant.

2022: Neural Progenitor Cells Engineered to Release GDNF Met the Trial’s Safety Endpoint

Transplantation of Human Neural Progenitor Cells Secreting GDNF Into the Spinal Cord of Patients With ALS: A Phase 1/2a Trial — Read Study

Eighteen people with ALS received unilateral transplantation of engineered human neural progenitor cells into the lumbar spinal cord, designed to release glial cell line-derived neurotrophic factor (GDNF). The study met its primary one-year safety endpoint, and investigators observed sustained graft survival and GDNF production in post-mortem tissue. The trial did not demonstrate an overall motor-neuron protective effect, but established an important proof of concept for combining cell and gene therapy approaches in ALS research.

2020: Wharton’s Jelly MSC Study Reported Longer Survival Compared With Matched Historical Controls

Umbilical Cord Mesenchymal Stem Cells in Amyotrophic Lateral Sclerosis: An Original Study — Read Study

This case-control study followed 67 people with ALS who received three intrathecal injections of Wharton’s jelly-derived MSCs approximately two months apart, matched with 67 reference patients from the PRO-ACT clinical-trial database. The authors reported approximately two-fold longer median survival in the treated group, with ALSFRS-R progression slowing in 21 participants and no serious adverse drug reactions reported. Because the comparison relied on matched historical controls rather than randomized concurrent controls, larger randomized trials are needed.

2019: Long-Term Follow-Up Supported the Feasibility of Intraspinal Neural Stem Cell Delivery

Results From Phase I Clinical Trial With Intraspinal Injection of Neural Stem Cells in Amyotrophic Lateral Sclerosis: A Long-Term Outcome — Read Study

Eighteen people with ALS received direct microinjections of human neural stem cells into the lumbar or cervical spinal cord and were followed for as long as 60 months. The investigators reported no severe treatment-related adverse effects or evidence that the procedure accelerated disease progression, providing important feasibility evidence that helped support later-phase research using higher cell doses and more advanced cell-engineering strategies.