A double-blind placebo-controlled clinical trial of subcutaneous recombinant human ciliary neurotrophic factor (rHCNTF) in amyotrophic lateral sclerosis

Neurology

Volumn 46, Issue 5, 1996, Pages 1244-1249

  Cedarbaum, J M ^a   Brooks, Benjamin R ^b  

^a REGENERON PHARMACEUTICALS INC   (United States)

^b University of Wisconsin Health   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CILIARY NEUROTROPHIC FACTOR;

ADULT; AMYOTROPHIC LATERAL SCLEROSIS; ANOREXIA; APHTHOUS STOMATITIS; ARTICLE; ASTHENIA; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; COUGHING; DISEASE COURSE; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; FEVER; HUMAN; MAJOR CLINICAL STUDY; MALE; MORTALITY; MULTICENTER STUDY; MUSCLE ISOMETRIC CONTRACTION; MUSCLE STRENGTH; NAUSEA; PHASE 2 CLINICAL TRIAL; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SUBCUTANEOUS DRUG ADMINISTRATION; WEIGHT REDUCTION;

EID: 2442646665     PISSN: 00283878     EISSN: None     Source Type: Journal    
DOI: 10.1212/wnl.46.5.1244     Document Type: Article

References (24)

1. Stockli KA, Lottspeich F, Sendtner M, et al. Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor. Nature 1989;342:920-923.
2. Wong V, Arriaga R, Ip NY, Lindsay RM. The neurotrophins BDNF, NT-3 and NT-4/5, but not NGF, up-regulate the cholinergic phenotype of developing motor neurons. Eur J Neurosci 1993;5:466-474.
3. Helgren ME, Wong V, Kennedy M, et al. Ciliary neurotrophic factor (CNTF) slows the progression of motor dysfunction in the Mnd mouse. Presented as "Works in Progress" at the forty-fourth Annual Meeting of the American Academy of Neurology, May, 1992.
4. Mitsumoto H, Ikeda K, Holmlund T, et al. The effects of ciliary neurotrophic factor (CNTF) on motor dysfunction in wobbler mouse motor neuron disease. Ann Neurol 1994;36:142-149.
5. Ikeda K, Holmlund T, Mitsumoto H, et al. Histometric effects of ciliary neurotrophic factor (CNTF) on motor dysfunction in wobbler mouse motor neuron disease. Ann Neurol 1995;37:47-54.
6. Sendtner M, Schmalbruch H, Stockli KA, et al. Ciliary neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuronopathy. Nature 1992; 358:502-504.
7. Helgren ME, Squinto SP, Davis HL, et al. Trophic effect of ciliary neurotrophic factor on denervated skeletal muscle. Cell 1994;76:493-504.
8. Gurney ME, Yamamoto H, Kwon Y. Induction of motor neuron sprouting in vivo by ciliary neurotrophic factor and basic fibroblast growth factor. J Neurosci 1992;12:3241-3247.
9. Kwon YW, Gurney ME. Systemic injections of ciliary neurotrophic factor induce sprouting by adult motor neurons. Neuroreport 1994;5:789-792.
10. ALS CNTF Treatment Study (A.C.T.S.) Phase I-II Study Group. The pharmacokinetics of subcutaneously administered recombinant human ciliary neurotrophic factor (rHCNTF) in patients with amyotrophic lateral sclerosis: relationship to parameters of the acute phase response. Clin Neuropharmacol 1995;18:500-514.
11. ALS CNTF Treatment Study (A.C.T.S.) Phase I-II Study Group. A phase I study of recombinant human ciliary neurotrophic factor (rHCNTF) in patients with amyotrophic lateral sclerosis. Clin Neuropharmacol 1995;18:515-532.
12. Stahl N, Yancopoulos GD. The alphas, betas and kinases of cytokine receptor complexes. Cell 1993;74:587-590.
13. Schooltink H, Stoyan T, Roeb E, Heinrich PC, Rose-John S. Ciliary neurotrophic factor induces acute-phase protein expression in hepatocytes. FEBS Lett 1992;314:280-284.
14. Fantuzzi G, Benigni F, Sironi M, et al. Ciliary neurotrophic factor (CNTF) induces serum amyloid A, hypoglycaemia and anorexia, and potentiates IL-1 induced corticosterone and IL-6 production in mice. Cytokine 1995;7:150-156.
15. Andres PL, Hedlund W, Finison L, et al. Quantitative motor assessment in amyotrophic lateral sclerosis. Neurology 1986; 36:937-941.
16. Brooks B, Sufit R, DePaul R, Tan Y, Sanjak M, Robbins J. Design of clinical therapeutic trials in amyotrophic lateral sclerosis. Adv Neurol 1991;56:521-546.
17. ALS CNTF Treatment Study (A.C.T.S.) Phase I-II Study Group. The ALS Functional Rating Scale: assessment of activities of daily living in patients with amyotrophic lateral sclerosis. Arch Neurol 1996;53:141-147.
18. Dittrich F, Thoenen H, Sendtner M. Ciliary neurotrophic factor: pharmacokinetics and acute-phase response in the rat. Ann Neurol 1994;35:151-163.
19. Henderson JT, Seniuk NA, Richardson PM, Gauldie J, Roder JC. Systemic administration of ciliary neurotrophic factor induces cachexia in rodents. J Clin Invest 1994;93:2632-2638.
20. Ip NY, Nye SH, Boulton TG, Davis S, et al. CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal-transducing receptor component gp 130. Cell 1992;69:1121-1132.
21. Nesbitt JE, Fuentes NL, Fuller GM. Ciliary neurotrophic factor regulates fibrinogen gene expression in hepatocytes by binding to the interleukin-6 receptor. Biochem Biophys Res Commun 1993;190:544-550.
22. Kriesel JD, Araneo B, Petajan JP, et al. Herpes labialis associated with recombinant human ciliary neurotrophic factor. J Infect Dis 1994;170:1046.
23. Miller RG, Armon C, Barohn R, et al. A controlled trial of recombinant human ciliary neurotrophic factor (rhCNTF) in amyotrophic lateral sclerosis (ALS). Ann Neurol 1996;39:256-260.
24. Mitsumoto H, Ikeda K, Wong V, et al. Arrest of motor neuron disease in wobbler mice cotreated with CNTF and BDNF. Science 1994;265:1107-1110.