A PHASE-I STUDY OF RECOMBINANT HUMAN CILIARY NEUROTROPHIC FACTOR (RHCNTF) IN PATIENTS WITH AMYOTROPHIC-LATERAL-SCLEROSIS

Fifty-seven patients with amyotrophic lateral sclerosis (ALS) were ran domly assigned to receive 0.5, 1, 3, 7, 10, or 30 mu g/kg recombinant human ciliary neurotrophic factor (rHCNTF) or placebo subcutaneously 3 times a week for 2 weeks. Dose-limiting toxicity, consisting of febri le reactions in some patients, fatigue, and nonproductive cough, was o bserved at a dose level of 30 mu g/kg. Dose-related changes in paramet ers of the acute-phase response were noted, consistent with the relati onship of CNTF and its receptor system to the cytokine interleukin-6 ( IL-6) and its receptor. No adverse neurologic consequences of rHCNTF a dministration were observed. Antibodies to rHCNTF were observed in ser a of most patients tested after 2 weeks of continuous treatment and 4 weeks' withdrawal period. rHCNTF was safe and tolerated within accepta ble limits when administered to patients with ALS in this study at dos es of up to 30 mu g/kg 3 times a week for 2 weeks. Further studies to explore the efficacy of rHCNTF in the treatment of human motor neuron diseases are justified.