Hi cl!
Another article which show importance of the continuos and site-specific delivery of the NT-3, CNTF, and BDNF for therapeutic effects in PD and ALS.
From Nature-Medicine:
medicine.nature.com
Adenoviral gene transfer of ciliary neurotrophic factor and brain-derived neurotrophic factor leads to long-term survival of axotomized motor neurons
Claude Gravel1, Rudolf G”tz2, Ann Lorrain1 & Michael Sendtner2 1Laboratoire de transfert de gŠnes, Centre de recherche Universit‚ Laval Robert-Giffard, 2601, de la CanardiŠre, Beauport,
Que., Canada G1J 2G3 2Klinische Forschergruppe Neuroregeneration, Department of Neurology, University of Wuerzburg, Josef-Schneider-Strasse 11, D-97080 Wuerzburg, Germany Correspondence should be addressed to M.S.
The neurotrophic factors ciliary neurotrophic factor and brain-derived neurotrophic factor can prevent motor neuron cell death during development1,2 and after nerve lesion in neonatal rodents3,4. However, local and systemic application of these factors to newborn rats with damaged motor nerves rescues motor neurons only transiently during the first two weeks after axotomy5,6. In order to test the effect of continuous delivery of these factors, the effect of localized injection of CNTF- or BDNF-transducing recombinant adenoviruses into the lesioned nerves was investigated. Under such conditions, survival of axotomized motor neurons is maintained for at least 5 weeks. This way of delivery corresponds to the physiological situation in adult rodents, under which endogenous CNTF is present in the cytosol of Schwann cells and BDNF expression is upregulated after nerve lesion, making these factors available to the damaged motor neurons7,8. Recent results show that overexpression of muscle-derived neurotrophin-3 prevents degeneration of axons and motor endplates, but has only little effect on the number of motor neuron cell bodies in a murine animal model of motor neuron disease9 . Therefore, techniques suitable for tonic exposure to both nerve- and muscle-derived neurotrophic factors may have implications for the design of future therapeutic strategies against human motor neuron disease.
mz |
