Gene therapy against neurological insults: sparing neurons versus sparing function.
Increasing knowledge of neuron death mediators has led to gene therapy techniques for neuroprotection. Overexpression of numerous genes enhances survival after necrotic or neurodegenerative damage. Nonetheless, although encouraging, little is accomplished if a neuron is spared from death, but not from dysfunction. This article reviews neuroprotection experiments that include some measure of function, and synthesizes basic principles relating to its maintenance. Variations in gene delivery systems, including virus-type and latency between damage onset and vector delivery, probably impact the therapeutic outcome. Additionally, functional sparing might depend on factors related to insult severity, neuron type involved or the step in the death cascade that is targeted.
Dumas
T C
TC
Dept of Biological Sciences, Stanford University, Stanford, CA 94305, USA. tedd1@stanford.edu
Sapolsky
R M
RM
D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000503:physiopathology* / Q000628:therapy*; D009474:Neurons / Q000502:physiology*