Animal models neurodegenerative diseases

It shows significant activity against a spectmm of neurodegenerative disorders in animal models that replicate many of the features of important human neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Parkinson s disease [147]. 

The use of a combination of neurotrophic factors in the treatment of neurodegenerative disease may well prove an avenue worthy of consideration. For example, pre-clinical studies reveal that administration of a combination of CNTF and BDNF to Wobbler mice (an animal model of motor neuron disease), prevented progression of motor neuron dysfuction, whereas administration of either factor on its own only slowed progression of the disease. 

In terms of clinical proof of neuroprotective effects in chronic neurodegenerative diseases, so far there are promising clinical results in ATS only with riluzole, and even then, the increase of survival obtained was only modest. The failure of r emacemide in a recent study in Huntington s disease was clearly a big setback. On the other hand, the moderate-affinity NMDA receptor antagonist memantine provides clear symptomatic improvement in dementia in both clinical and preclinical situations, and the precHnical data predict neuroprotective effects, substantiated by numerous animal models. 

AMPA receptor antagonists acting at the 2,3-benzodiazepine modulatory site seem to have a better safety profile than competitive agents such as NBQX, probably due to their better solubility and associated reduced side-effects such as renal toxicity. It is still not clear for which indications they might be useful, although their effects in animal models of acute and chronic neurodegenerative diseases look quite promising. 

StemCells, Inc. is developing a proprietary NSC product for cellular therapy, under license from NeuroSpheres Ltd., comprising well-characterized, normal human CNS stem cells (HuCNS-SCs) from brain tissue. HuCNS-SC is currently under investigation for the potential treatment of neurodegenerative disorders, particularly BD [180367], [540074]. Preclinical studies have been performed in various animal models of CNS diseases and injuries. Data from these studies has supported the therapeutic potential of HuCNS-SCs, and the therapy has recently been approved for a phase I clinical trial for the treatment of BD [629732]. 

In 1987, however, a study by Busto et al. (5) showed that small decreases in brain temperature (as little as 2-5°C below normal brain temperature) conferred a marked protective effect against experimental global cerebral ischemia. This finding, as well as subsequent animal studies that modeled neurodegenerative diseases and CNS injury, led to a resurgence of interest in mild hypothermia as a method of cerebral protection. 

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