Slowing or arresting disease progression in amyotrophic lateral sclerosis (ALS) may be in sight, results from a pilot study suggest.
A team of Israeli researchers from the Hadassah-Hebrew University Medical Center in Jerusalem and Tel Aviv University developed a culture-based method to induce mesenchymal-stem–cell (MSC) to secrete neurotrophic growth factors (NTFs) and conducted a 2-part open-label proof-of-concept trial to assess the safety and efficacy of autologous MSC-NTF cell transplantation in patients with ALS.1
The trial, published in JAMA Neurology, consisted of a 3-month run-in period, a cell transplantation phase, and a 6-month follow-up. Twelve patients between the ages of 20 and 75 years who fulfilled the El-Escorial criteria for ALS were enrolled in the first part of the trial. Of these, 6 with early-stage ALS (baseline ALS Functional Rating Scale–Revised [ALS-FRS-R] >30) were injected intramuscularly and 6 with more advanced disease (ALS-FRS-R score <30 and >15 and forced vital capacity [FVC] >50%) were transplanted intrathecally. Intramuscular (IM) injections were delivered at 1 × 106 cells/site to 24 separate sites in the biceps and triceps, and intrathecal (IT) injections were given at a dose of 1 × 106/kg cells. Peripheral blood, muscle mass, and compound muscle action potentials were assessed at regular intervals during follow-up.
The second part of the trial was a phase 2a dose-escalating study. In it, 14 patients with early-stage ALS received both IM and IT injections and were divided into low (1 × 106 cells/kg IT and 24 × 106 cells IM), moderate (1.5 × 106 cells/kg IT and 36 × 106 cells IM), and high (2 × 106 cells/kg IT and 48 × 106 cells IM) dosing cohorts.
Safe and Potentially Therapeutic
At follow-up assessment, IT, IM, and IT plus IM administration of MSC-NTF cells was determined to be relatively safe, with most adverse events (eg, headache, back or leg pain, vomiting) being low grade and transient. No significant changes in any laboratory parameters, including blood counts, biochemistry, renal and hepatic function, thyroid function, or urinalysis were seen, and imaging did not reveal any significant pathology at injection sites.