Ciba Foundation Symposium 196 - Growth Factors as Drugs for by CIBA Foundation Symposium

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Degeneration of sensory receptors or of the nerves innervating them results in a sensory deficit. a variety of recommendations were attempted for selling regrowth of sensory receptors, rather within the eye and ear. the most recent facts from experimental stories in animals are offered within the ebook together with functions of BDNF and CNTF within the eye and epidermal progress consider the ear.

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Kuplun: We don’t know. Rafl: What about in in vitro experiments? If you give a pulse of N G F for an hour and then remove it, is it still effective? Kuplun: Our main models have been in PC12 cells and 3T3 cells expressing Trk. There, NGF-induced TrkA tyrosine phosphorylation persists only for a few hours. So in vivo there’s a marked difference in what we see. Ruff; Presumably then, there’s a pool that stays around, even if no one has found it. Kaplun: Or it could be that in vivo there’s a desensitized receptor; or that the phosphatases that normally take those tyrosine phosphates off are not functioning.

Consequently, the motor neuron now innervates hundreds more endplates than normal. Over time, as you begin to drive this over-compensated neuronal population, the neuron simply gets ‘tired’ and becomes gradually ineffective. The projections tend to retract, the muscle weakens and deteriorates, there is a loss of function and the motor neuron dies. We have utilized the same models and rationale used for ALS to suggest utility of rhIGF-1 in post-polio. In the current trial that we are considering on postpolio, one challenge we face is that to show a positive clinical benefit will require six months to a year of dosing.

J Neurobiol 25~759-766 Neff NT, Prevette D, Houenou LJ et al 1993 Insulin-like growth factors: putative muscle-derived trophic agents that promote motoneuron survival. J Neurobiol 24: 1578-1 588 Rinderknecht E, Humbel R E 1978 Amino acid sequence of human insulin-like growth factor 1 and its structural homology with proinsulin. J Biol Chem 235:2769-2776 Rosenthal SM, Hsiao D, Cheng ZQ, Silverman LA 1994 Insulin-like growth factors and muscle cell differentiation. In: Baxter RC, Gluckman PD, Rosenfeld R G (eds) The insulin-like growth factors and their regulatory proteins: proceedings of the third international symposium on insulin-like growth factors, Sydney, February 1994.

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