A phase 1/2a clinical trial resulted in showing that a single dosing of AstroRx was safe and tolerable, at either a low or high dose, for patients with ALS.
Recently, in a phase 1/2a, open-label, dose-escalating clinical trial (NCT03482050), results demonstrated a transplantation of a single dose of AstroRx (Kadimastem) cells is safe for patients with ALS.1 These findings provide evidence for assessing the cells in an attempt to compensate for the malfunctioning of the astrocytes of patients with ALS in a randomized, placebo-controlled, multidose clinical trial for ALS.
The trial included a low dose of 100 x 106 cells and high dose of 250 x 106 cells, which are composed of healthy and functional human astrocytes derived from human embryonic stem cells.1 The majority of patients (70%) experienced transient adverse events (AEs) following the lumbar puncture procedure for the cell transplantation, though all were resolved. Before and after treatment, the ALSFRS-R change comparison showed a significant decline, with at least a 50% rate reduction in disease progression. Notably, the decline was also consistent over the first 3-months after the treatment.
Michal Izrael, PhD, and colleagues presented an abstract at the 2022 Annual Northeast Amyotrophic Lateral Sclerosis (NEALS) Meeting, November 1-3, in Clearwater Beach, Florida, on these outcomes. Izrael, vice president, research and development for ALS and diabetes, Kadimastem Ltd, Nes-Ziona, Israel, and colleagues noted that the findings indicate that AstroRx was tolerable, supporting the cell transplantation as a clinical signal for a therapeutic benefit for patients with ALS.
Five patients each were given an injection by lumbar puncture of the single low dose or a high dose. During a 3-month period of pretreatment and follow-up after 12-months post treatment, the safety and motor function were recorded for assessment. There were no AEs reported that were related to the AstroRx cells. In both doses, there was a consistency in the beneficial effect, which the authors noted was more profound in those deemed rapid progressors. Between the periods of pretreatment and posttreatment, there were no significant changes observed in the ALS assessment questionnaire scores or serum biomarkers.
Similarly, in a previous study of AstroRx done by Izrael and colleagues, the findings demonstrated that immunosuppressive activity of AstroRx provided evidence for it being a cell therapy treatment for acute respiratory distress syndrome (ARDS).2 Additionally, the researchers observed that the immunoregulatory activity could be a part of the mechanism of action of AstroRx that has been reported in ALS.
In the study with AstroRx in ARDS, a portion of the mice treated with the cells (30%) had no lung lesions. Additionally, the mice that were AstroRx-treated presented a steady number of eosinophils, T cells, and neutrophils along with having a higher survival rate.2 The ability of the AstroRx to suppress T-cell proliferation was assessed in a mixed lymphocyte reaction test and used a severity scoring scale of 0-2 based on the American Thoracic Society to assess the degree of lung injury.