=============================================================== == == == ----------- ALS INTEREST GROUP ----------- == == ALS Digest (#46, 29 MAY 1993) == == == == To subscribe, to unsubscribe, to contribute notes, etc. == == to ALS Digest, please send e-mail to: == == bro@huey.met.fsu.edu (Bob Broedel) == == == == All interested people may "broadcast" messages to == == ALS Digest subscribers by sending to: == == als@huey.met.fsu.edu == == == =============================================================== In order to get the back issues, one should send e-mail to: LISTSERV@mailer.fsu.edu Then in the body of your message say (it ignores the subject line) GET ALS ALSD01 GET ALS ALSD02 GET ALS ALSD03 etc. To join the ALS-related discussion on that LISTSERV, send e-mail to: LISTSERV@mailer.fsu.edu In the body of the message say ... SUBSCRIBE ALS yourfirstname yourlastname (1) ===== rhGH (recombinant human Growth Hormone) and ALS ========== >Date : 28 May 1993 11:47:20 -0500 (EST) >From : ROSEN@HELIX.MGH.HARVARD.EDU >Subject: Re: als 45 > >An article in the journal Muscle and Nerve (June, 1993, Vol.16, >pp. 624-633) entitled "Recombinant Growth Hormone Treatment of >Amyotrophic Lateral Sclerosis" concludes that "This (research) >suggests that rhGH (recombinant human Growth Hormone) did not >appear to influence the course of ALS as judged by careful >measurement of disease progression using the TQNE (the Tufts >Quantitative Neuromuscular Examination, a numerical scale for >assessment of disease status)." This study was conducted by >R.A. Smith, S. Melmed, B. Sherman, J. Frane, Ted Munsat, and >Barry Festoff. > Dr. Rosen, Many thanks to you for sending this info. Our library subscribes to that journal but the June issue has not yet arrived here in the provinces. Also, I often get confused by the terminology (i.e. growth factors, nerve growth factors, growth hormones, insulin- related growth factors, recombinant growth hormones etc.). Is there any relationship between this rhGF article and the current CNTF clinical trials? Thanks, Bro (2) ===== CNTF (some background info) ========== Here is something I lifted from one of the bioscience gophers. This particular article came from the database "Online Mendelian Inheritance in Man (OMIN)". Oddly, it gives no idea as to the author, the title of the journal, publication date, etc. -- sorry. bro 118945 CILIARY NEUROTROPHIC FACTOR [CNTF] Barbin et al. (1984) described the neurotrophic activity of ciliary neurotrophic factor purified from chick eye employing a survival assay for neurons from chick embryonic ciliary ganglia. In addition to neurotrophic effects on parasympathetic neurons, CNTF was shown to have activities on sympathetic and sensory neurons. CNTF was purified to homogeneity from rat and rabbit sciatic nerve, enabling the isolation of cDNAs encoding the factor. Based on the cDNA sequences, Lam et al. (1991) designed synthetic oligonucleotide probes which were used in the isolation of the human CNTF gene. They described the amino acid sequence of human CNTF as well as the organization of the gene which was located on chromosome 11 by analysis of human-hamster somatic cell hybrids. The human protein showed approximately 85% identity with CNTF of rat and rabbit. It is of note that brain-derived neurotrophic factor (BDNF; 113505) is located on 11p13 and that neurotrophic factor 3 (NTF3; 162660) is located on chromosome 12, which shows considerable homeology with chromosome 11. Kaupmann et al. (1991) demonstrated that the homologous gene is on mouse chromosome 19 and that its expression is unaffected in the mouse neurologic mutant Wobbler (wr), a form of spinal muscular atrophy. Using a rodent/human somatic cell DNA mapping panel and fluorescence in situ hybridization, Lev et al. (1993) localized the CNTF gene to the proximal region of 11q. In addition, they identified a polymorphic tandem CA/GT dinucleotide repeat associated with the human CNTF gene. To sublocalize the CNTF gene on chromosome 11, Giovannini et al. (1993) isolated cosmid clones containing the gene by use of a chromosome 11-specific library. Using these clones in fluorescence in situ hybridization, they found that the gene maps at an FLpter of 0.46, corresponding to a cytogenetic band position of 11q12.2, according to the method of Lichter et al. (1990). Homozygous pmn/pmn mice have a progressive motor neuronopathy which becomes evident in the hind limbs at the end of the third postnatal week; all the mice die of respiratory paralysis 6 or 7 weeks after birth. Sendtner et al. (1992) found that treatment with ciliary neurotrophic factor prolonged survival and greatly improved motor function in these mice and reduced the morphologic manifestations of the neural degeneration, even though treatment did not start until the first symptoms of disease had become apparent and substantial degenerative changes were already present. Because CNTF has a short half-life and because pmn mice do not tolerate daily injections of CNTF and are too small to accommodate infusion pumps, the agent was delivered by intraperitoneal injection of a mouse cell line transfected with a genomic construct that releases high quantities of biologically active CNTF. The mode of action is not known. The CNTF and the CNTF-processing pathways are not perturbed in pmn. Furthermore, CNTF appears not to be involved in motoneuron survival during development. The observations, whatever their explanation, hold hope for the treatment of amyotrophic lateral sclerosis (105400) and related disorders. Barbin, G.; Manthorpe, M. and Varon, S.: Purification of the chick eye ciliary neuronotrophic factor. J. Neurochem. 43: 1468-1478, 1984. Giovannini, M.; Romo, A. J. and Evans, G. A.: Chromosomal localization of the human ciliary neurotrophic factor gene (CNTF) to 11q12 by fluorescence in situ hybridization. Cytogenet. Cell Genet. 63: 62-63, 1993. Kaupmann, K.; Sendtner, M.; Stockli, K. A. and Jockusch, H.: The gene for ciliary neurotrophic factor (CNTF) maps to murine chromosome 19 and its expression is not affected in the hereditary motoneuron disease 'Wobbler' of the mouse. Europ. J. Neurosci. 3: 1182-1186, 1991. Lam, A.; Fuller, F.; Miller, J.; Kloss, J.; Manthorpe, M.; Varon, S. and Cordell, B.: Sequence and structural organization of the human gene encoding ciliary neurotrophic factor. Gene 102: 271-276, 1991. Lev, A. A.; Rosen, D. R.; Kos, C.; Clifford, E.; Landes, G.; Hauser, S. L. and Brown, R. H., Jr.: Human ciliary neurotrophic factor: localization to the proximal region of the long arm of chromosome 11 and association with CA/GT dinucleotide repeat. Genomics 16: 539-541, 1993. Lichter, P.; Chang Tang, C.; Call, K.; Hermanson, G.; Evans, G. A.; Housman, D. and Ward, D.: High-resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones. Science 247: 63-69, 1990. Sendtner, M.; Schmalbruch, H.; Stockli, K. A.; Carroll, P.; Kreutzberg, G. W. and Thoenen, H.: Ciliary neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuronopathy. Nature 358: 502-504, 1992. == end of als 46 ==