For the first time a translational study indicates the muscle a potential therapeutic target for amyotrophic lateral sclerosis
ALS is a neurodegenerative disease affecting motor neurons. It leads to progressive paralysis of skeletal muscle, causes the loss of the ability to swallow and articulate speech, and can lead to compromising respiratory muscles and causing a respiratory arrest. Pierangelo Cifelli is researcher at Ri.MED Foundation. After training at the University of Pittsburgh he is currently working at Eleonora Palma's laboratory at the Department of Physiology and Pharmacology, University of Rome Sapienza, after a scientific agreement between the two institutions. Dr. Cifelli is co-author of Acetylcholine receptors from human muscle as pharmacological targets for ALS therapy, a study recently published on the prestigious scientific journal PNAS*. 76 patients affected with ALS and 17 patients with a clinical picture of denervation caused by other pathologies were enrolled for this study at the Centro Malattie Neuromuscolari Rare [Center for Rare Neuromuscular Diseases] of Policlinico Umberto I in Rome. This new innovative technique involves microtransplanting muscle membranes from selected ALS patients into oocytes of a frog native of South Africa that is able to blend human membranes exposing all native proteins on their membrane. Using specific electrophysiological techniques, it was also possible to study the electrical current due to the activation of muscle receptors, and effects of endocannabinoid palmitoylethanolamide (PEA) whose results on the muscular strength had been previously demonstrated on one ALS patient. The hypothesis was that PEA could boost the activity of muscles that remain continuously stimulated, such as the respiratory muscles. Results showed PEA can reduce the decline of forced vital capacity (FVC) of patients and significantly improve their respiratory performance. The outcomes of the translational study reinforce the hypothesis that muscle participates to the evolution of ALS and indicate it as a new potential therapeutic target, suggesting the need to identify pathological biomarkers also in the muscle, not only in motor neurons, during the pre-symptomatic phase of the disease. Dr. Cifelli is very satisfied with these results: "The suggested approach is potentially revolutionary as it paves the way for research on a muscular level, and not necessarily neuronal. These results are a special reward for me in professional terms, after three years of work, and as a human being, as this study allowed me to translate basic research into clinical research. Of course, I wish to thank Ri.MED Foundation for its support, and Prof. Palma and Prof. Inghilleri for giving me the opportunity to participate in such an important study." The Ri.MED Foundation is focused on the translation of preclinical research in experimental medicine for patients. *Acetylcholine receptors from human muscle as pharmacological targets for ALS therapy Eleonora Palma (a,b), Jorge Mauricio Reyes-Ruiz (c), Diego Lopergolod, Cristina Roseti (b), Cristina Bertollini (a), Gabriele Ruffolo (a), Pierangelo Cifelli (e, a), Emanuela Onesti (d), Cristina Limatola (a,f), Ricardo Miledi (c,g), Maurizio Inghilleri (d) a) Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome Sapienza, Rome, Italy; b) IRCCS San Raffaele Pisana, Rome, Italy; c) Department of Neurobiology and Behavior, University of California Irvine, CA, USA; d) Department of Neurology and Psychiatry, University of Rome Sapienza, Rome, Italy; e) Ri.MED Foundation Palermo, Italy; f) IRCCS Neuromed, Pozzilli, Italy; g) Instituto de Neurobiología, Querétaro, México.
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Italy, United States