Italian Study: A Pilot Trial Of LDN In Primary Progressive Multiple Sclerosis

[Garnet]

Link to Article Abstract:
http://msj.sagepub.com/cgi/content/abstract/14/8/1076

Link to Full Text Article:
http://msj.sagepub.com/cgi/reprint/14/8/1076

A Pilot Trial Of Low Dose Naltrexone In Primary Progressive Multiple Sclerosis

M Gironi
Institute of Experimental Neurology (INSPE) and Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 58, Milan, Italy; Fondazione Don Carlo Gnocchi, IRCCS, Milan, Italy

F Martinelli-Boneschi
Institute of Experimental Neurology (INSPE) and Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 58, Milan, Italy

P Sacerdote
Department of Pharmacology, University of Milan, Milan, Italy

C Solaro
Department of Neurology, ASL 3 genovese, Genoa, Italy

M Zaffaroni
Multiple Sclerosis Study Center, Hospital of Gallarate, Gallarate (VA), Italy

R Cavarretta
Fondazione Don Carlo Gnocchi, IRCCS, Milan, Italy

L Moiola
Institute of Experimental Neurology (INSPE) and Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 58, Milan, Italy

S Bucello
Institute of Experimental Neurology (INSPE) and Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 58, Milan, Italy

M Radaelli
Institute of Experimental Neurology (INSPE) and Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 58, Milan, Italy

V Pilato
Multiple Sclerosis Study Center, Hospital of Gallarate, Gallarate (VA), Italy

ME Rodegher
Institute of Experimental Neurology (INSPE) and Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 58, Milan, Italy

M Cursi
Institute of Experimental Neurology (INSPE) and Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 58, Milan, Italy

S Franchi
Department of Pharmacology, University of Milan, Milan, Italy

V Martinelli
Institute of Experimental Neurology (INSPE) and Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 58, Milan, Italy

R Nemni
Fondazione Don Carlo Gnocchi, IRCCS, Milan, Italy

G Comi
Institute of Experimental Neurology (INSPE) and Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 58, Milan, Italy

G Martino
Institute of Experimental Neurology (INSPE) and Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 58, Milan, Italy martino.gianvito@hsr.it

A sixth month phase II multicenter-pilot trial with a low dose of the opiate antagonist Naltrexone (LDN) has been carried out in 40 patients with primary progressive multiple sclerosis (PPMS). The primary end points were safety and tolerability. Secondary outcomes were efficacy on spasticity, pain, fatigue, depression, and quality of life. Clinical and biochemical evaluations were serially performed. Protein concentration of β-endorphins (BE) and mRNA levels and allelic variants of the µ-opiod receptor gene (OPRM1) were analyzed. Five dropouts and two major adverse events occurred. The remaining adverse events did not interfere with daily living. Neurological disability progressed in only one patient. A significant reduction of spasticity was measured at the end of the trial. BE concentration increased during the trial, but no association was found between OPRM1 variants and improvement of spasticity. Our data clearly indicate that LDN is safe and well tolerated in patients with PPMS.

Key Words: β-endorphins • efficacy • low-dose naltrexone • opioid receptors • primary progressive multiple sclerosis • safety


Multiple Sclerosis, Vol. 14, No. 8, 1076-1083 (2008)
DOI: 10.1177/1352458508095828