Abstract Recent studies indicate that minocycline exerts neuroprotective effects in vitro and in vivo, and suggest that the drug may represent a novel therapeutic approach to amyotrophic lateral sclerosis (ALS). In this study we investigated the safety of combined treatment with minocycline and riluzole in ALS. Twenty ALS patients were randomised into two groups and administered either riluzole (50 mg b.i.d.) or riluzole and minocycline (100 mg i.d.) for 6 months. Disease progression was measured by means of the ALS-Functional Rating Scale score at month- ly intervals. Respiratory function was measured at the beginning of the study and repeated after 3 and 6 months of treatment. Combined treatment with minocycline and riluzole was not followed by significant side effects. This pilot study shows that minocycline and riluzole can be taken safely together. Further trials are needed to assess efficacy of such treatment. Key words Amyotrophic lateral sclerosis • Minocycline • Riluzole • Clinical trial Introduction Amyotrophic lateral sclerosis (ALS) is a chronic progres- sive neuromuscular condition of unknown aetiology, char- acterised by muscle wasting, weakness, fasciculations and increased reflexes [1]. Respiratory failure is the most fre- quent cause of death. In recent years, numerous therapeutic trials have been carried out on ALS. One drug, riluzole, proved to slightly prolong survival of ALS patients in two controlled trials [2, 3]. However, the therapeutic approach to the disease remains far from satisfactory. Recent studies indicate that minocycline, a tetracycline derivate, mediates neuroprotection in experimental models of neurodegeneration. Minocycline indirectly inhibits the activity of caspase-1, caspase-3, inducible form of nitric oxide synthetase (iNOS) and p38 mitogen-activated pro- tein kinase (MAPK) [4, 5]. The drug delays the onset and extends survival in ALS mice [6–8]. Because of the safe profile of minocycline and its ability to cross the blood–brain barrier, the drug may represent a novel thera- py for ALS. Moreover, experimental data suggest that minocycline and riluzole may have synergistic effects in ALS [9]. A recent study showed the safety of minocycline in ALS patients [10]. In this pilot study, we investigated the safety of combined treatment with minocycline and riluzole in ALS patients. Materials and methods Twenty patients with a diagnosis of probable or definite ALS, according to the El Escorial revised criteria of the World Federation of Neurology [11], were recruited consecutively at the Motor Neuron Diseases outpatient service of our institution in the period between 1 June and 30 November 2003. There were 12 males and 8 females (mean age 60±11 years, range 38–76; mean disease duration 16±6 months, range 8–27). All patients enrolled Neurol Sci (2005) 26:285–287 DOI 10.1007/s10072-005-0474-x F.E. Pontieri • A. Ricci • C. Pellicano • D. Benincasa • F.R. Buttarelli Minocycline in amyotrophic lateral sclerosis: a pilot study BRIEF COMMUNICATION Received: 11 April 2005 / Accepted in revised form: 12 July 2005 F.E. Pontieri () • C. Pellicano • D. Benincasa • F.R. Buttarelli Dipartimento di Scienze Neurologiche II Facoltà di Medicina e Chirurgia Università di Roma ‘La Sapienza’ Clinica Neurologica, Ospedale ‘Sant’ Andrea’ Via di Grottarossa 1035, I-00189 Rome, Italy e-mail: francesco.pontieri@ospedalesantandrea.it A. Ricci Dipartimento Malattie Cardiovascolari e Respiratorie II Facoltà di Medicina e Chirurgia Università di Roma ‘La Sapienza’ Rome, Italy