Stem Cell Therapy Safe, Shows Potential to Slow Progression in Trial

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Repeat injections of mesenchymal stem cells (MSCs) into the spinal canal were safe and well tolerated in patients with amyotrophic lateral sclerosis (ALS), and showed potential to significantly slow the rate of disease progression, a small Phase 2 clinical trial found.

“Larger studies are warranted to confirm our observations and further evaluate the therapeutic potential of cellular therapy in neurodegenerative diseases such as ALS,” the researchers wrote.

The study, “A phase II clinical trial with repeated intrathecal injections of autologous mesenchymal stem cells in patients with amyotrophic lateral sclerosis,” was published in Frontiers in Bioscience-Landmark by a team of researchers in Israel.

MSCs, which are capable of maturing into many other cell types, are found in several parts of the body, including the bone marrow, skin, and fat tissue. With their strong immunosuppressive, anti-inflammatory, neuroprotective, and regenerative properties, MSCs are gaining increasing interest as a potential therapeutic approach for a number of neurodegenerative conditions, including ALS.

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A transplant of MSCs typically involves collecting these cells from a patient, expanding them in the lab, and returning them to the patient by infusion or injection — either via the bloodstream (intravenous), spinal canal (intrathecal), or muscle tissue (intramuscular).

A few Phase 1/2 clinical trials have shown that MSCs are safe and able to slow disease progression in ALS patients. However, their effects seem to fade off with time, “possibly indicating the need of repeated injections,” the researchers wrote.

To evaluate the safety and tolerability of multiple injections of MSCs, and how well they work to slow disease progression, scientists in Israel conducted a Phase 2 clinical trial (NCT04821479) that enrolled 20 patients (16 men and four women), with a mean age of about 50 (49.97) and a mean disease duration of less than two years (20.61 months).

At the study’s beginning, their mean score on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) was 31.1; this scale ranks a patient’s functional abilities — in areas like speech, swallowing, dressing and hygiene, walking and climbing stairs, and breathing — on a scale of 0 to 48, with higher scores indicating better abilities.

To evaluate how fast disease was progressing before treatment, patients were followed during a run-in period that lasted a mean of 7.8 months. Eighteen (90%) had a progression rate greater than 0.5 points in ALSFRS-R each month, “indicating that this group consisted of patients with severe disease and bad prognosis,” the researchers wrote.

During that period, MSCs were taken from the bone marrow and grown in a lab before being injected back into the patients. One left the study before this procedure.

The remaining 19 were treated with one to four intrathecal injections of MSCs (1 million cells per kg of body weight), given at intervals of three to six months, and followed for up to six months after the last injection. Twelve patients had three injections and 10 had four.

No serious side effects related to treatment were reported. Three people had headache and back pain related to the spinal injection, and one experienced general weakness and fatigue for two weeks after injection.

“Adverse events that were considered related to the treatment were mostly mild and transient and occurred close to the time of cell administration,” the researchers wrote.

Among the 19 patients given at least one treatment, 13 experienced an overall reduction in their progression rate of over 25%, indicating a clinically meaningful change. The mean improvement — or reduction in the rate of progression — was 47%. Three other patients had an improvement of less than 25% and another three saw their condition worsen.

“There was a statistically significant reduction in the slope of progression after each one of all 4 cycles of transplantation, as compared to the deterioration during the pre-treatment period,” the researchers wrote.

For some patients, the therapy did more than slow the rate of disease progression — “clinical improvements [were] observed in several patients,” the researchers wrote. After the first treatment, seven patients experienced an improvement of one to four points in their ALSFRS-R scores, and five retained these gains after a second injection.

Of note, the time interval between first, second, and third injections was about three months. Between the third and fourth injection, the time interval was longer (about five months), and changes in the progression rate were more moderate.

“The response rate correlated with the time-intervals between the injections,” the researchers wrote.

Researchers also watched for changes in forced vital capacity (FVC), a measure lung function. Among the 11 patients with enough available data, lung function declined at a slower rate after treatment compared with measures taken in the run-in period, but findings here failed to reach statistical significance.

“Our data provide indications of clinically meaningful beneficial effects,” the researchers concluded.