Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030552 (paresis)
 5,831 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sterol storage disorder cerebrotendinous xanthomatosis (CTX) is characterized by abnormal deposition of cholesterol and cholestanol in multiple tissues. Deposition in the central nervous system leads to neurological dysfunction marked by dementia, spinal cord paresis, and cerebellar ataxia. Deposition in other tissues causes tendon xanthomas, premature atherosclerosis, and cataracts. In two unrelated patients with CTX, we have identified different point mutations in the gene (CYP27) encoding sterol 27-hydroxylase, a key enzyme in the bile acid biosynthesis pathway. Transfection of mutant cDNAs into cultured cells results in the synthesis of immunoreactive sterol 27-hydroxylase protein with greatly diminished enzyme activity. We have localized the CYP27 gene to the q33-qter interval of human chromosome 2, and to mouse chromosome 1, in agreement with the autosomal recessive inheritance pattern of CTX. These findings underscore the essential role played by sterols in the central nervous system and suggest that mutations in other sterol metabolizing enzymes may contribute to diseases with neurological manifestations.
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PMID:Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis. 201 2

Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid storage disease caused by mutations in the cytochrome P450(27) (CYP27) gene. This disease is characterized by the accumulation of a bile alcohol, cholestanol, in diverse tissues. Accumulation in the central nervous system leads to neurological dysfunction including dementia, spinal cord paresis, and cerebellar ataxia. Accumulation in other tissues causes tendon xanthomas, premature atherosclerosis, and cataracts. In a Japanese family with CTX, we identified two points mutations in the CYP27 gene at different sites. One is a novel transversion, which substitutes G for C at Pro 368 (CCC) to Arg (CGC). The other is a transition, which substitutes A for G at Arg441 (CGG) to Gln (CAG), this being the same mutation that Kim et al. reported (1994. J. Lipid Res. 35: 1031 - 1039). Allele-specific polymerase chain reaction analysis indicated that the father and mother of this family, who themselves had no clinical manifestations of CTX, had the former and latter mutations heterozygously, respectively. On the other hand, the patients each had both mutations heterozygously. These results are highly suggestive, but not conclusive, that the newly identified transversion in the CYP27 gene accounts for the sterol 27-hydroxylase (EC 1.14.13.15) deficiency in these patients.
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PMID:A novel mutation in the cytochrome P450(27) (CYP27) gene caused cerebrotendinous xanthomatosis in a Japanese family. 872 24

Chronic disability after stroke represents a major unmet neurologic need. ReNeuron's development of a human neural stem cell (hNSC) therapy for chronic disability after stroke is progressing through early clinical studies. A Phase I trial has recently been published, showing no safety concerns and some promising signs of efficacy. A single-arm Phase II multicenter trial in patients with stable upper-limb paresis has recently completed recruitment. The hNSCs administrated are from a manufactured, conditionally immortalized hNSC line (ReNeuron's CTX0E03 or CTX), generated with c-mycERTAM technology. This technology has enabled CTX to be manufactured at large scale under cGMP conditions, ensuring sufficient supply to meets the demands of research, clinical development, and, eventually, the market. CTX has key pro-angiogenic, pro-neurogenic, and immunomodulatory characteristics that are mechanistically important in functional recovery poststroke. This review covers the progress of CTX cell therapy from its laboratory origins to the clinic, concluding with a look into the late stage clinical future.
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PMID:Human Neural Stem Cell Therapy for Chronic Ischemic Stroke: Charting Progress from Laboratory to Patients. 2844 71