Ciliary neurotrophic factor
Ensembl | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 11: 58.62 – 58.63 Mb | Chr 19: 12.74 – 12.74 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Ciliary neurotrophic factor is a protein that in humans is encoded by the CNTF gene.[5][6][7]
The protein encoded by this gene is a
CNTF has also been shown to be expressed by cells on the bone surface, and to reduce the activity of bone-forming cells (osteoblasts).[8]
Therapeutic applications
Satiety effects
In 2001, it was reported that in a human study examining the usefulness of CNTF for treatment of
Recombinant human CNTF (Axokine)
A
Phase III clinical trials for the drug against obesity were conducted in 2003 by Axokine's maker, Regeneron Pharmaceuticals, demonstrating a small positive effect in some patients, but the drug was not commercialized. A major problem with the treatment was that in nearly 70% of the subjects tested, antibodies against Axokine were produced after approximately three months of treatment.[11] In the minority of subjects who did not develop the antibodies, weight loss averaged 12.5 pounds in one year, versus 4.5 pounds for placebo-treated subjects. In order to obtain this benefit, subjects needed to receive daily subcutaneous injections of one microgram Axokine per kilogram body weight.
Xencor patent application raises the disturbing idea that subjects producing antibodies against CNTF analogues may eventually suffer severe adverse effects, as these antibodies could potentially interfere with the neuroprotective functions of endogenous CNTF.[12] The application claims methods of designing CNTF analogues with lower immunogenicity than Axokine based on analysis of affinity of each modified epitope for each of 52 class II MHC alleles, and provides specific examples of such modifications. No such analogues are currently listed in Xencor's product pipeline.[13]
NT-501
NT-501 is a product being developed by Neurotech that consists of encapsulated human cells genetically modified to secrete ciliary neurotrophic factor (CNTF). In a clinical trial, NT-501 demonstrated a statistically significant reduction of photoreceptor degradation in patients with retinitis pigmentosa.[14][15]
Interactions
Human ciliary neurotrophic factor has been shown to
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000242689 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000079415 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 1840538.
- S2CID 24161982.
- ^ a b "Entrez Gene: CNTF ciliary neurotrophic factor".
- S2CID 23699865.
- PMID 11259650.
- PMID 10818143.
- ^ "Axokine from Regeneron (REGN): Unexpected Antibodies and Modest Efficacy in Phase III Study". Press Release. Regeneron Pharmaceuticals. 2003-03-31. Retrieved 2011-08-20.
- ^ US application 2005064555, Marshall S, Barbosa M, "Ciliary neurotrophic factor variants", published 2005-03-24
- ^ "Product Pipeline". Xencor. Retrieved 2011-08-20.
- PMID 21087953.
- ^ "Neurotech's NT-501 Implant Demonstrates Statistically Significant Photoreceptor Preservation in Patients with Retinal Degenerative Disease". Business Wire. 2011-04-11. Retrieved 2011-08-20.
- PMID 12643274.
- S2CID 39538295.
Further reading
- Sendtner M, Carroll P, Holtmann B, et al. (1995). "Ciliary neurotrophic factor". J. Neurobiol. 25 (11): 1436–53. PMID 7852996.
- Sleeman MW, Anderson KD, Lambert PD, et al. (2000). "The ciliary neurotrophic factor and its receptor, CNTFR alpha". Pharmaceutica Acta Helvetiae. 74 (2–3): 265–72. PMID 10812968.
- Schooltink H, Stoyan T, Roeb E, et al. (1993). "Ciliary neurotrophic factor induces acute-phase protein expression in hepatocytes". FEBS Lett. 314 (3): 280–4. S2CID 39538295.
- Masiakowski P, Liu HX, Radziejewski C, et al. (1991). "Recombinant human and rat ciliary neurotrophic factors". J. Neurochem. 57 (3): 1003–12. S2CID 7965554.
- McDonald JR, Ko C, Mismer D, et al. (1991). "Expression and characterization of recombinant human ciliary neurotrophic factor from Escherichia coli". Biochim. Biophys. Acta. 1090 (1): 70–80. PMID 1883844.
- Negro A, Tolosano E, Skaper SD, et al. (1991). "Cloning and expression of human ciliary neurotrophic factor". Eur. J. Biochem. 201 (1): 289–94. PMID 1915374.
- Lichter P, Tang CJ, Call K, et al. (1990). "High-resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones". Science. 247 (4938): 64–9. PMID 2294592.
- Winter CG, Saotome Y, Levison SW, Hirsh D (1995). "A role for ciliary neurotrophic factor as an inducer of reactive gliosis, the glial response to central nervous system injury". Proc. Natl. Acad. Sci. U.S.A. 92 (13): 5865–9. PMID 7597043.
- Yokoji H, Ariyama T, Takahashi R, et al. (1995). "cDNA cloning and chromosomal localization of the human ciliary neurotrophic factor gene". Neurosci. Lett. 185 (3): 175–8. S2CID 26711154.
- McDonald NQ, Panayotatos N, Hendrickson WA (1995). "Crystal structure of dimeric human ciliary neurotrophic factor determined by MAD phasing". EMBO J. 14 (12): 2689–99. PMID 7796798.
- Saggio I, Paonessa G, Gloaguen I, et al. (1995). "Nonradioactive receptor binding assay for ciliary neurotrophic factor". Anal. Biochem. 221 (2): 387–91. PMID 7810882.
- Takahashi R, Yokoji H, Misawa H, et al. (1994). "A null mutation in the human CNTF gene is not causally related to neurological diseases". Nat. Genet. 7 (1): 79–84. S2CID 5606065.
- Giovannini M, Romo AJ, Evans GA (1993). "Chromosomal localization of the human ciliary neurotrophic factor gene (CNTF) to 11q12 by fluorescence in situ hybridization". Cytogenet. Cell Genet. 63 (1): 62–3. PMID 8449041.
- Robledo O, Auguste P, Coupey L, et al. (1996). "Binding interactions of leukemia inhibitory factor and ciliary neurotrophic factor with the different subunits of their high affinity receptors". J. Neurochem. 66 (4): 1391–9. S2CID 35399535.
- Gutman CR, Strittmatter WJ, Weisgraber KH, Matthew WD (1997). "Apolipoprotein E binds to and potentiates the biological activity of ciliary neurotrophic factor". J. Neurosci. 17 (16): 6114–21. PMID 9236223.
- Cargill M, Altshuler D, Ireland J, et al. (1999). "Characterization of single-nucleotide polymorphisms in coding regions of human genes". Nat. Genet. 22 (3): 231–8. S2CID 195213008.
External links
- Ciliary+neurotrophic+factor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Overview of all the structural information available in the PDB for UniProt: P26441 (Ciliary neurotrophic factor) at the PDBe-KB.
PDB gallery | |
|---|---|
|
