There is no satisfactory treatment for amyotrophic lateral sclerosis (ALS) [ 11. Ciliary neurotrophic factor (CNTF) is an endogenous protein that is released upon injury to the nervous system and limits the extent of injury-induced tieuronal damage in some nerve cells [2, 31. CNTF can be produced in large quantities by recombinant DNA techniques. It promotes the survival of motor neurons in animal models of nerve injury, and in murine motor neuron disease [4].
Placebo-controlled, Phase I trials in patients with ALS indicated that subcutaneous doses of recombinant human CNTF (rhCNTF) up to 5 Fg/kg/day were generally well tolerated [5]. Higher doses produce unacceptable toxicity [5, 61. We report the results of a prospective, randomized, double-blind placebo-controlled trial in 570 patients with ALS. Preclinical investigations indicated that recombinant human ciliary neurotrophic factor (rhCNTF) may have potential as therapy for amyotrophic lateral sclerosis (ALS). We evaluated the safety and efficacy of rhCNTF in a prospective, double-blind, placebo-controlled trial in 570 patients with U S . Patients were randomized to receive 0.5, 2, or 5 pglkglday rhCNTF, or placebo, for 6 months. The primary efficacy end point was the change from baseline to the last on-treatment value of a combination megascore for limb strength (maximum voluntary isometric contraction) and pulmonary function. Secondary end points included individual arm and leg megascores, pulmonary function tests, an activities-of-daily-living outcome measure, and survival. The four treatment groups were similar at baseline with respect to age, sex, disease duration, and muscle strength values. At all doses tested,
rhCNTF had no beneficial effect on the primary or secondary end points. Certain adverse events, as follows, appeared to be dose related: injection site reactions, cough, asthenia, nausea, anorexia, weight loss, and increased salivation. There was an increased number of deaths at the highest dose level. rhCNTF had no benefical effect on any measure of ALS progression. There were increased adverse events in the 5 pglkg group and increased deaths.