Safety of intrathecal autologous adipose-derived mesenchymal stromal cells in patients with ALS

Abstract

Objective: To determine the safety of intrathecal autologous adipose-derived mesenchymal stromal cell treatment for amyotrophic lateral sclerosis (ALS).Methods: Participants with ALS were enrolled and treated in this phase I dose-escalation safety trial, ranging from 1 3 10 7 (single dose) to 1 3 10 8 cells (2 monthly doses). After intrathecal treatments, participants underwent standardized follow-up, which included clinical examinations, revised ALS Functional Rating Scale (ALSFRS-R) questionnaire, blood and CSF sampling, and MRI of the neuroaxis.Results: Twenty-seven patients with ALS were enrolled and treated in this study. The safety profile was positive, with the most common side effects reported being temporary low back and radicular leg pain at the highest dose level. These clinical findings were associated with elevated CSF protein and nucleated cells with MRI of thickened lumbosacral nerve roots. Autopsies from 4 treated patients did not show evidence of tumor formation. Longitudinal ALSFRS-R questionnaires confirmed continued progression of disease in all treated patients.Conclusions: Intrathecal treatment of autologous adipose-derived mesenchymal stromal cells appears safe at the tested doses in ALS. These results warrant further exploration of efficacy in phase II trials. Classification of evidence:This phase I study provides Class IV evidence that in patient with ALS, intrathecal autologous adipose-derived mesenchymal stromal cell therapy is safe.

Concise Review: A Safety Assessment of Adipose-Derived Cell Therapy in Clinical Trials: A Systematic Review of Reported Adverse Events

“…Almost all organ system have been implicated in adipose‐derived cell therapy. The indication for treatment in the included studies was (in order count) soft tissue , gastrointestinal , musculoskeletal , rheumatological , ulcer/ischemic limb , urogenital , cardiac , neurological , immunological , pulmonary , and ophthalmological (Fig. A).…”

A Combination of Intrathecal and Intramuscular Application of Human Mesenchymal Stem Cells Partly Reduces the Activation of Necroptosis in the Spinal Cord of SOD1G93A Rats

“…We compared three injections of cells or their CondM applied at intervals of 14 days into SC, or cells injected into M, or a combination of both applications—SC + M. We used lumbar puncture as a route of delivery. This is the most common way of how ALS patients are treated with different types of stem cells . In our previous study, we reported a prolonged lifespan and an improved neurological outcome in the SOD1 rats treated with hMSC in one single injection into cisterna magna at the onset of the disease.…”

“…The most recent clinical investigations, in patients with ALS who underwent hMSC transplantation, have shown procedural safety and clinical proof of principle with modest neurological benefits. The most frequently used route of delivery in patients is via lumbar puncture, either in single dose or repeatedly .…”

Repeated Intrathecal Mesenchymal Stem Cells for Amyotrophic Lateral Sclerosis

“…With the advancement of stem cell research, diverse types of stem cell therapy have been conducted; however, randomized controlled trials on cell-based therapies for ALS were not published until early 2016. To date, most clinical trials of MSCs for ALS were single-arm phase 1 22,23 or phase 2 24 trials focusing on the safety, feasibility, and possible efficacy, whereas only a few compared natural historical data. 25,26 In this study, 2 repeated treatments with intrathecal autologous BM-MSCs (1 × 10 6 cells per kg with a 26-day interval) showed significant therapeutic benefit with safety in patients with ALS.…”