Progesterone as a new treatment option for Amyotrophic Lateral Sclerosis patients: open trial and survival analysis”

GARGIULO MONACHELLI GM; RODRIGUEZ G; GONZALEZ DENISELLE M.C; DE NICOLA AF; SICA REP

Congreso; 60th Annual Meeting of the American Academy of Neurology; 2008

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease in which oxidative stress and glutamatergic excitotoxicity play an etiopathogenic role. Thus,our objective was to determine if progesterone therapy -with antioxidant properties- prolongs survival in ALS. Progesterone has shown neuroprotective, promyelinating and antioxidant effects on central-peripheral nervous system and motoneuron disease animal models. It has proven to be safe in a human phase II traumatic brain injury trial. A series of patients with definite or probable ALS (n=26) were selected between 2002 and 2003. Patients with a predicted forced vital capacity (FVC) < 50%, gastrostomy and on wheelchair were excluded. They were given oral progesterone (300 mg daily for 22.5 18.41 months, n=6), riluzole (100 mg daily for 17.12 14.09 months, n=7), or riluzole plus progesterone (R+P for 21.1 11.63 months, n=11). Evaluations were conducted every 2 months using the Medical Research Council MRC) muscular strength scale, the Norris and ALSFRS functional rating scales,and the FVC. Survival was considered from onset of symptoms to attrition or June 2007. The survival curves were compared using the Kaplan-Meier method. Adverse events were registered at each visit. A trend for longer survival was obtained in the progesterone and in the riluzole plus progesterone groups versus the riluzole only group (55.5 14.6 and 60.09 8.46 months versus 38.14 9.4 months respectively) without reaching statistical significance (p=0.38). Differences in FVC, muscular strength or functional measures were not apparent between the three groups. Adverse effects were minimally associated with progesterone treatment, few complained of somnolence or gastrointestinal symptoms. At the dose studied, patients receiving progesterone in association with riluzole showed a trend toward longer survival and proved to be free of major collateral effects. Further studies are warranted to disclose if combined therapy with progesterone might be a successful neuroprotective therapy option for ALS patients.