Israeli treatment could delay deadly effects of ALS – new study

AstroRx is a cell therapy product containing functional healthy astrocytes derived from human embryonic stem cells that aim to protect diseased motor neurons.

AstroRx cells (photo credit: Courtesy)
AstroRx cells
(photo credit: Courtesy)
The Israeli company Kadimastem says it hopes to soon be in discussion with the Food and Drug Administration to advance the company’s AstroRx cells, after demonstrating promising results with cohort A of its Phase 1/2a clinical trial for the treatment of patients with Amyotrophic Lateral Sclerosis (ALS). 
“We plan on having discussions this year in order to get regulatory clarity as to the next steps of our trial and in hopes that the results of this study will support the advancement to the next multi-center clinical trial in ALS,” said Hadas (Dasy) Mandel, Kadimastem’s director of business development.
Kadimastem’s AstroRx has the ability to replace the functioning of damaged cells using Allogeneic (off-the-shelf) stem cells.
“While cells are unable to directly replace diseased motor neurons, stem cells can be differentiated into central nervous system-supportive cells, such as astrocytes,” a release by the company explains. The astrocytes, also known as nervous system support cells, secrete neurotrophic factors and remove toxic substances surrounding malfunctioning neurons, thereby providing neuroprotection that can slow degeneration of motor neurons. 
Cohort A of its Phase 1/2a clinical trial included five patients, each treated with a dose of 100x10⁶ AstroRx cells developed by the company and who then completed the six months of post-treatment follow up. Company CEO Rami Epstein said that, after checking disease progression in patients before and after the trial according to the ALS Functional Rating Scale-Revised (ALSFRS-R) – the gold standard criteria to assess ALS progression – the results showed that “our treatment is effective” for supporting the malfunctioning cells in the brain and spinal cord, in order to slow the progression of the disease and improve patients’ quality of life and life expectancy. 
During the three month program of pre-treatment, patient muscle function decreased at an average rate of -0.87 per month, as per the ALSFRS-R scale, a rate similar to that reported in the scientific literature. 
In positive contrast, the average ALSFRS-R change in the three months post-treatment was +0.26 per month. 
“These results demonstrate a statistically significant difference between the slope in the pre-treatment period and the slope in the three month post-treatment period,” said Epstein. 
Similarly, improvements were noted in the fourth month of the post treatment period, though not in months five and six. Epstein said this indicates that a higher dose and/or repeated administrations may achieve prolonged efficacy, both of which will be tested in the coming months among cohorts B and C of this clinical trial.
Furthermore, there were no treatment-related serious adverse events or dose-limiting toxicities reported during the six-month post-treatment follow up period of cohort A.
The trial is taking place at Hadassah Medical Center in Jerusalem. Kadimastem is based in Ness Ziona.
ALS is a rapidly progressive, fatal neurodegenerative disease-causing dysfunction in the upper and lower motor nerves that control muscle function. A release shared by the company described the disease’s symptoms as including muscle weakness, loss of motor function, paralysis, breathing problems and eventually death. 
According to Epstein, most people diagnosed with ALS live only up to five years from the time of diagnosis. According to the ALS Therapy Development Institute, there are approximately 450,000 ALS patients worldwide.
Specifically, AstroRx is a cell therapy product containing functional healthy astrocytes derived from human embryonic stem cells that aim to protect diseased motor neurons. The cells are injected in the patient through the spinal canal.
The company initiated its first ALS clinical trials in March 2018.
Prof. Michel Revel, founder and CEO of the company and winner of both the EMET Prize and the Israel Prize, said that the clinical trial results “provide the confidence needed to move forward” with cohorts B and C, which he said both “hold the potential for a prolonged response.”
Cohort B involves patients taking a higher dose; C involves repeated treatments.
Revel added that the treatment’s positive safety profile will also allow the company to test AstroRx in other neuro-degenerative diseases as well.