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ALS, or amyotrophic lateral sclerosis, is a fatal neurodegenerative disease that progresses fast. The symptoms include loss of motor skills, with inflamed nerve cells and nerve cell death playing a prominent role. Nerve cells are spread throughout your body and control voluntary muscle control, such as speaking, walking, running, breathing, etc. As ALS progresses, nerve cells start to die at a rapid rate. As a result, a person’s mobility is greatly reduced. This disease gradually paralyzes the patient and death is often a result of respiratory failure. 

Because this disease is so fast acting and deadly, scientists are hoping to find a treatment. Researchers think a cell-based therapy, which is a type of treatment that uses the patient’s or a donor’s cells to try to treat a disease, has potential to be a treatment for the many symptoms of the disease. 

Stem cells that come from the adult bone marrow, called mesenchymal stem cells, secrete high levels of molecules called factors that promote growth of nervous tissue. These nerve tissue stem cells have been shown to promote the production of molecules in the cerebral spinal fluid that protect nerve tissue. The researchers hypothesized that if ALS patients were injected with these mesenchymal nerve stem cells, it could slow the progression of the ALS. 

To test this hypothesis, they recruited 189 patients with ALS between the ages of 18 and 60 and divided them into two groups – a placebo group and a test group. The study was carried out double-blinded, meaning that researchers, patients, lab-technicians, and all personnel did not know who had placebo and who had the real treatment. One half received the stem cell treatment and the other half received a placebo. Forty-five patients dropped out of the test before it was finished. The average age of the subjects was 49 years old and 67% were male.

To measure how much the patients improved, they were given a test called the ALSFRS-R, or the ALS Functional Rating Scale-Revised. This test works by giving each patient a simple motion to do. They are then scored from 0 (cannot move at all) to 4 (normal motion). The lower the patient’s total score,  the worse the disease has gotten and the more limited the patient’s motor skills are. 

Only 31% of participants scored greater than or equal to 35, the highest score being 48, on their motor function ability, which means most of the patients had more advanced ALS. During the study, a total of 16 people died, all of whom had more advanced ALS than the average patient in the study. There were no safety concerns related to taking the stem cell treatment. 

Each month the patient’s motor skills were measured using the ALSFRS-R test, and a cerebral spinal fluid sample was taken. The researchers also measured biomarkers, or molecules in blood that can indicate disease. These tests include three specific molecules — vascular endothelial growth factor (VEGF), Monocyte chemoattractant protein-1 (MCP-1), and neurofilament light chain proteins (NfL). VEGF indicates that new blood vessels are forming and is usually lower in ALS patients. MCP-1 regulates part of the immune system and is usually higher in ALS patients. NfL indicates the death of neurons and is usually higher in ALS patients.

About 77% of the patients had advanced ALS and 33% had less advanced ALS according to the results. Almost all the patients experienced some side-effects from treatment, including those with the placebo. However, very few symptoms were severe. For patients who received the stem cell treatment, their disease’s progression did not slow down compared to those who had the placebo, and there were no differences between the two groups with more advanced ALS.  

There were also no statistically significant differences between motor skill test scores in the placebo group and the treatment group  However, stem cell patients did show improvements in the three biomarkers. There was an increase in VEGF, the protein that promotes new blood vessels. MCP-1 levels were down, which regulates the immune system. NfL levels were also lower, which means fewer dead neurons.

These results were important for knowing the response to the treatment and supports the idea that treatment with mesenchymal nerve stem cells could work as a treatment to slow the progression of ALS. In conclusion, while the treatment did not successfully slow the progression of ALS, the study did provide helpful information for improvements to make to stem cell treatments in future studies.

Study Information

Original study: A randomized placebo-controlled phase 3 study of mesenchymal stem cells induced to secrete high levels of neurotrophic factors in amyotrophic lateral sclerosis

Study published on: 10 December 2021

Study author(s): Merit E. Cudkowicz MD,Stacy R. Lindborg PhD,Namita A. Goyal MD,Robert G. Miller MD,Matthew J. Burford MD,James D. Berry MD,Katharine A. Nicholson MD,Tahseen Mozaffar MD,Jonathan S. Katz MD,Liberty J. Jenkins MD,Robert H. Baloh MD,Richard A. Lewis MD,Nathan P. Staff MD,Margaret A. Owegi DO,Donald A. Berry PhD,Yael Gothelf PhD,Yossef S. Levy PhD,Revital Aricha PhD,Ralph Z. Kern MD,Anthony J. Windebank MD,Robert H. Brown Jr MD

The study was done at: California Institute for Regenerative Medicine (USA)

The study was funded by: Amyotrophic Lateral Sclerosis Association; California Institute for Regenerate Medicine

Raw data availability: Not available

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