TY - JOUR
T1 - A phase I study of recombinant human ciliary neurotrophic factor (rHCNTF) in patients with amyotrophic lateral sclerosis
AU - Cedarbaum, J. M.
AU - Chapman, C.
AU - Charatan, M.
AU - Stambler, N.
AU - Andrews, L.
AU - Zhan, C.
AU - Radka, S.
AU - Morrisey, D.
AU - Lakings, D.
AU - Brooks, B. R.
AU - Sanjak, M.
AU - Pestronk, A.
AU - Florence, J.
AU - Mitsumoto, H.
AU - Szirony, K.
AU - Bittle, L.
AU - Ringel, S.
AU - Neville, H.
AU - Brinkmann, J.
AU - Wittes, J.
PY - 1995
Y1 - 1995
N2 - Fifty-seven patients with amyotrophic lateral sclerosis (ALS) were randomly assigned to receive 0.5, 1, 3, 7, 10, or 30 μg/kg recombinant human ciliary neurotrophic factor (rHCNTF) or placebo subcutaneously 3 times a week for 2 weeks. Dose-limiting toxicity, consisting of febrile reactions in some patients, fatigue, and nonproductive cough, was observed at a dose level of 30 μg/kg. Dose-related changes in parameters of the acute-phase response were noted, consistent with the relationship of CNTF and its receptor system to the cytokine interleukin-6 (IL-6) and its receptor. No adverse neurologic consequences of rHCNTF administration were observed. Antibodies to rH-CNTF were observed in sera of most patients tested after 2 weeks of continuous treatment and 4 weeks' withdrawal period. rHCNTF was safe and tolerated within acceptable limits when administered to patients with ALS in this study at doses of up to 30 μg/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.
AB - Fifty-seven patients with amyotrophic lateral sclerosis (ALS) were randomly assigned to receive 0.5, 1, 3, 7, 10, or 30 μg/kg recombinant human ciliary neurotrophic factor (rHCNTF) or placebo subcutaneously 3 times a week for 2 weeks. Dose-limiting toxicity, consisting of febrile reactions in some patients, fatigue, and nonproductive cough, was observed at a dose level of 30 μg/kg. Dose-related changes in parameters of the acute-phase response were noted, consistent with the relationship of CNTF and its receptor system to the cytokine interleukin-6 (IL-6) and its receptor. No adverse neurologic consequences of rHCNTF administration were observed. Antibodies to rH-CNTF were observed in sera of most patients tested after 2 weeks of continuous treatment and 4 weeks' withdrawal period. rHCNTF was safe and tolerated within acceptable limits when administered to patients with ALS in this study at doses of up to 30 μg/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.
KW - Amyotrophic lateral sclerosis
KW - Ciliary neurotrophic factor
KW - rHCNTF
UR - https://www.scopus.com/pages/publications/0028788303
U2 - 10.1097/00002826-199512000-00004
DO - 10.1097/00002826-199512000-00004
M3 - Article
C2 - 8681312
AN - SCOPUS:0028788303
SN - 0362-5664
VL - 18
SP - 515
EP - 532
JO - Clinical Neuropharmacology
JF - Clinical Neuropharmacology
IS - 6
ER -