Immunomodulation 2Saturday, October 13, 2007, 15:30 - 17:00
Pilot multicentric study of low dose naltrexone in primary progressive multiple sclerosisM. Gironi, F. Martinelli Boneschi, C. Solaro, R. Cavarretta, M. Zaffaroni, L. Moiola, S. Bucello, M. Radaelli, V. Pilato, M. Rodegher, M. Cursi, V. Martinelli, R. Nemni, G. Comi, P. Sacerdote, G. Martino (Milan, Genoa, Gallarate, I)
Preliminary evidence have documented an interesting symptomatic effect of low dose naltrexone (LDN) on spasticity, pain and fatigue whose control remains an unmet need for patients (pts) with Primary Progressive Multiple Sclerosis (PPMS). Naltrexone is an orally semi synthetic opiate antagonist licensed, in a 50 mg dose, for the treatment of heroin addiction. However, when Naltrexone is given at very lower doses (up to 5 mg), its opiate antagonist activity is completely abrogated while triggering a prolonged up regulation of endorphins (BE). The LDN-induced increase of BE is supposed to have an anti-inflammatory effect.
We have approached a 6-months, pilot, multicentric, open-label, therapeutic study with LDN aimed at evaluating its safety and efficacy on spasticity, pain and fatigue occurring in 40 pts with PPMS Clinical and biochemical evaluations are performed at different time points during the study. Appropriate scale for testing spasticity, pain and fatigue (e.g. Ashworth, Fatigue Severity Scale, Visual Analogue Scale) are used as an integral part of the periodical neurological examination. BE levels in peripheral blood mononuclear cells are also measured by radioimmunoassay.
So far, 40 pts with a diagnosis of PPMS, according to McDonald criteria, (19 male, mean age 53.4, mean age at onset 41.2, mean EDSS 5.5) have been enrolled in the study. Optimization of gabaergic and/or serotoninergic drugs has been performed in all pts before the enrolment. Opioid-containing-drug, immunosuppressive or immunomodulator drugs were considered as a contraindication to study enrolment.
At present, all PPMS pts have completed the 4° month of therapy. Transitory haematological abnormalities (increase of liver enzymes, hypercholesterolemia), mild agitation and sleep disturbance were the commonest adverse events. Only two drop-outs occurred (one for protocol violation and one for severe increase of hypertonia). In conclusion, LDN has shown, so far, to be a safe treatment in PPMS. We are now collecting and analysing efficacy results.