| 摘要 |
This invention defines novel research and clinical laboratory methodology and compositions related thereto appropriate for use in (a) determining the presence of a neurodegenerative disease selected from the group limited solely to Charcot-Marie-Tooth disease, familial Alzheimer's disease, familial Parkinson's disease, Huntington's disease, spinal muscular atrophy, Friedreich'a ataxia, giant axon neuropathy, juvenile ceroid-lipofuscinosis, familial motor neuron diseases, juvenile diabetic polyneuropathy and Down's syndrome, (b) monitoring the ongoing status of the physiological expression of said disease and (c) screening candidate therapeutic drug agents for possible effectiveness. The invention is based on the new and novel observation that the presence of a neurodegenerative disease can be characterized in part by the expression in cultured fibroblasts obtained from the patient of one or more proteins which are not the product of a defective disease-inducing gene, but which are stress proteins, one or more other proteins modified by conditions of oxidative stress or one or more other disease-related proteins. The invention depends on living cell material, namely fibroblasts, which are readily and, if necessary, repeatedly available from a patient. When adapted as a method and composition useful for the screening candidate therapeutic drug agents for possible effectiveness, this technology offers advantages in terms of (a) providing research opportunities which, in some cases, never existed before, (b) cost effectiveness when compared to alternative technologies, (c) ability to be used readily on a large scale, (d) ability to generate meaningful data in a comparatively short period of time, and (e) providing an early stage opportunity to obtain information based on direct interaction of a candidate drug and a living tissue disease model. Various aspects of diagnostic methods and compositions are also disclosed.
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