![]() ![]() 8 - 10 The benefits of MSC treatment were attributed to significant upregulation of various NTFs, especially the glial-derived neurotrophic factor (GDNF) and basic fibroblast growth factor. Systemic or intraspinal bone marrow or adipose-derived mesenchymal stem cell (MSC) transplantation has been reported to delay motor neuron degeneration and improve motor performance in the mouse model of ALS. Indeed, studies in animal models of neurodegenerative diseases have shown that NTF-secreting cells induce neuroprotective effects. 1, 2 A more effective approach might be direct delivery of multiple NTFs to the central nervous system through transplantation of cells that actively secrete these factors. Although neurotrophic factors (NTFs) have been shown to extend the survival of motor neurons in ALS, peripheral administration of single NTFs has not revealed any benefit. The biological mechanisms underlying amyotrophic lateral sclerosis (ALS) are only partially understood, and there is currently no effective treatment that can significantly halt or reverse disease progression. Trial Registration Identifiers: NCT01051882 and NCT01777646 Of these patients, 13 (87%) were defined as responders to either ALS Functional Rating Scale–Revised or forced vital capacity, having at least 25% improvement at 6 months after treatment in the slope of progression.Ĭonclusions and Relevance The results suggest that IT and IM administration of MSC-NTF cells in patients with ALS is safe and provide indications of possible clinical benefits, to be confirmed in upcoming clinical trials. ![]() The rate of progression of the forced vital capacity and of the ALS Functional Rating Scale–Revised score in the IT (or IT+IM)–treated patients was reduced (from −5.1% to −1.2%/month percentage predicted forced vital capacity, P < .04 and from −1.2 to 0.6 ALS Functional Rating Scale–Revised points/month, P = .052) during the 6 months following MSC-NTF cell transplantation vs the pretreatment period. Most of the adverse effects were mild and transient, not including any treatment-related serious adverse event. Results Among the 12 patients in the phase 1/2 trial and the 14 patients in the phase 2a trial aged 20 and 75 years, the treatment was found to be safe and well tolerated over the study follow-up period. Secondary end points included the effects of the treatment on various clinical parameters, such as the ALS Functional Rating Scale–Revised score and the respiratory function. Main Outcomes and Measures The primary end points of the studies were safety and tolerability of this cell therapy. ![]() Interventions Patients were administered a single dose of MSC-NTF cells. In the second stage, a phase 2a dose-escalating study, 14 patients with early-stage ALS received a combined IM and IT transplantation of autologous MSC-NTF cells. In the phase 1/2 part of the trial, 6 patients with early-stage ALS were injected intramuscularly (IM) and 6 patients with more advanced disease were transplanted intrathecally (IT). All patients were followed up for 3 months before transplantation and 6 months after transplantation. Objective To determine the safety and possible clinical efficacy of autologous MSC-NTF cells transplantation in patients with ALS.ĭesign, Setting, and Participants In these open-label proof-of-concept studies, patients with ALS were enrolled between June 2011 and October 2014 at the Hadassah Medical Center in Jerusalem, Israel. These MSC-NTF cells have been shown to be protective in several animal models of neurodegenerative diseases. We have developed a culture-based method for inducing mesenchymal stem cells (MSCs) to secrete neurotrophic factors. Importance Preclinical studies have shown that neurotrophic growth factors (NTFs) extend the survival of motor neurons in amyotrophic lateral sclerosis (ALS) and that the combined delivery of these neurotrophic factors has a strong synergistic effect. Shared Decision Making and Communication.Scientific Discovery and the Future of Medicine.Health Care Economics, Insurance, Payment.Clinical Implications of Basic Neuroscience.Challenges in Clinical Electrocardiography. ![]()
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