Exploiting neurotrophic factors for the treatment of neurodegenerative conditions: An Australian perspective
✍ Scribed by Richard A. Hughes; Paul D. O'Leary
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 155 KB
- Volume
- 46
- Category
- Article
- ISSN
- 0272-4391
No coin nor oath required. For personal study only.
✦ Synopsis
Neurotrophic factors are proteins which promote the growth, survival, and differentiation of neurons. The ability of neurotrophic factors to prevent the degeneration of neurons following nerve lesion and in genetic models of neurodegeneration suggest that they offer therapeutic potential in the treatment of neurodegenerative diseases. However, despite their promising biology, Phase III clinical trials with recombinant neurotrophic factor proteins administered subcutaneously to patients with amyotrophic lateral sclerosis have yielded disappointing results. Australian research groups, in their studies on neurotrophic factor action, are examining alternative means of exploiting neurotrophic factor systems for clinical gains, including antisense techniques to shut down apoptosis signaling via the low-affinity neurotrophin receptor p75 in damaged neurons; ligand-based molecular design methods to develop small molecules from neurotrophic factor templates, with the goal of producing neurotrophic drugs with improved pharmacokinetic behaviour; and glycosaminoglycans as agents to stimulate endogenous fibroblast growth factors and their receptors in neurons, as well as preparing the groundwork for clinical studies with as yet untested factors, such as leukaemia inhibitory factor. Success with these approaches, along with other strategies such as improved drug delivery systems, increase the likelihood that neurotrophic factor systems will be used effectively in the near future for the treatment of neurodegenerative disorders.