Acetylcholine Receptors From Human Muscles as Pharmacological Target for ALS (AchALS)

Amyotrophic lateral sclerosis (ALS) is a fatal disease leading to motor neuron degeneration and progressive paralysis. Other studies have revealed defects in skeletal muscle even in absence of motor neuron anomalies, focusing on acetylcholine receptors (AChRs) and supporting the so-called "dying-back" hypothesis. Outcome of this study will be to understand if the endocannabinoid palmitoylethanolamide (PEA) can reduce the rundown of AChRs currents in ALS muscle, and if it can modify ALS patients' clinical and electrophysiological parameters.

Outcome: Monitoring the efficacy and safety of PEA in the treatment of patients with ALS. Analysis of AChR currents and description of the composition of AChRs subunits in ALS muscles Design of the Study: A randomized controlled blinded study. Patients with sporadic ALS will receive riluzole alone or riluzole+PEA in order to investigate the clinical and electrophysiological effects of treatment. The expected number of enrolled patients will be 50. All patients satisfying the selection criteria will be randomized into two groups: a first group will be treated only with riluzole, the second group with riluzole associated with PEA (Normast 600 mg microgranular, 2 sachets/day). The randomization will be done stratifying patietns according to type of clinical onset (bulbar vs. spinal). The patients will be enrolled in the Department of Neurology and Psychiatry, University of Rome "Sapienza". The visits will be performed at 0 (randomization), 3 and 6 months. At each visit the ALS Functional Rating Scale-Revised (ALSFRS-R), the percentage of predicted forced vital capacity (FVC%), the Medical Research Council (MRC) score for muscle strength limited to the right upper limbs, and the compound muscle action potentials (CMAP) from right ulnar and phrenic nerves will be assessed. A muscle biopsy will be done at the end of the study. The obtained results will be compared with those observed in muscle samples from denervated (non-ALS) control patients.

Riluzole 50 mg twice daily plus Endocannabinoid palmitoylethanolamide (PEA) (ultramicronized) 600 mg twice daily in ALS patients

Changes in acetylcholine receptors (AChR) currents and Analysis of the composition of AChRs subunits in ALS muscles.

Utilization of voltage-clamp intracellular recordings in oocytes transplanted with membranes from ALS muscles.

Changes of the compound muscle action potential (CMAP) amplitude of ulnar and phrenic nerves will be measured

Inclusion Criteria: Diagnosis of ALS according to the El-Escorial criteria; Age> 18 years; ALS Functional Rating Scale-Revised (ALSFRS- r) score> 20; Forced Vital Capacity (FVC)> 30%; Treatment with Riluzole. Exclusion Criteria: Other diseases motor neurons; Experimental treatments in the previous three months; Pregnant or breast-feeding; Contraindications to the use of riluzole; Patients undergoing tracheostomy, enteral or parenteral supply; Severe psychiatric disorders.