Targets in ALS: designing multidrug therapies.

Abstract:

:Amyotrophic lateral sclerosis (ALS) is an incurable disease that arises from the progressive loss of motoneurons. Even when caused by a single gene defect, as in the case of mutations in the enzyme Cu-Zn superoxide dismutase (SOD1), ALS is the result of a complex cascade that involves crosstalk among motoneurons, glia and muscles, and evolves through the action of converging toxic mechanisms. Transgenic rodents that express human mutant SOD1 and develop a progressive paralytic disease are widely used to screen potential therapeutics. Treatments that interfere with a specific event in the neurotoxic cascade have been reported to produce a modest increase in rodent lifespan. Multi-intervention approaches, including novel methods to intercept the damage and to deliver molecules to vulnerable cells, have recently been shown to be more effective. Thus, new avenues for promising therapeutic approaches can be derived from multidrug treatments and/or the delivery of growth factors by viral vectors, in combination with exercise and/or diet regimens.

journal_name

Trends Pharmacol Sci

authors

Carrì MT,Grignaschi G,Bendotti C

doi

10.1016/j.tips.2006.03.009

subject

Has Abstract

pub_date

2006-05-01 00:00:00

pages

267-73

issue

5

eissn

0165-6147

issn

1873-3735

pii

S0165-6147(06)00083-6

journal_volume

27

pub_type

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