Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied absorption, efficacy, and tolerability in Parkinson's disease (PD) of a new preparation of apomorphine included in a microemulsion and administered by transdermal route (Apo-MTD). Twenty-one PD patients were treated with levodopa plus oral dopamine-agonists (T0), with levodopa alone (T1), finally with levodopa plus Apo-MTD (T2). Apo-MTD provided therapeutic plasma levels for many hours, improved Unified Parkinson's Disease Rating Scale III scores, and reduced total duration of off periods compared to T0 and T1. We concluded that Apo-MTD is absorbed and demonstrates clinical efficacy and long action. Therefore, it seems a promising add-on treatment for uncontrolled prolonged off phases in PD patients, but chronic tolerability needs further study.
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PMID:Transdermal apomorphine permeation from microemulsions: a new treatment in Parkinson's disease. 1530 Jun 60

Neurodegeneration in Parkinson's disease (PD) affects mainly dopaminergic neurons in the substantia nigra, where age-related, increasing percentages of cells lose detectable respiratory activity associated with depletion of intact mitochondrial DNA (mtDNA). Replenishment of mtDNA might improve neuronal bioenergetic function and prevent further cell death. We developed a technology ("ProtoFection") that uses recombinant human mitochondrial transcription factor A (TFAM) engineered with an N-terminal protein transduction domain (PTD) followed by the SOD2 mitochondrial localization signal (MLS) to deliver mtDNA cargo to the mitochondria of living cells. MTD-TFAM (MTD = PTD + MLS = "mitochondrial transduction domain") binds mtDNA and rapidly transports it across plasma membranes to mitochondria. For therapeutic proof-of-principle we tested ProtoFection technology in Parkinson's disease cybrid cells, using mtDNA generated from commercially available human genomic DNA (gDNA; Roche). Nine to 11 weeks after single exposures to MTD-TFAM + mtDNA complex, PD cybrid cells with impaired respiration and reduced mtDNA genes increased their mtDNA gene copy numbers up to 24-fold, mtDNA-derived RNAs up to 35-fold, TFAM and ETC proteins, cell respiration, and mitochondrial movement velocities. Cybrid cells with no or minimal basal mitochondrial impairments showed reduced or no responses to treatment, suggesting the possibility of therapeutic selectivity. Exposure of PD but not control cybrid cells to MTD-TFAM protein alone or MTD-TFAM + mtDNA complex increased expression of PGC-1alpha, suggesting activation of mitochondrial biogenesis. ProtoFection technology for mitochondrial gene therapy holds promise for improving bioenergetic function in impaired PD neurons and needs additional development to define its pharmacodynamics and delineate its molecular mechanisms. It also is unclear whether single-donor gDNA for generating mtDNA would be a preferred therapeutic compared with the pooled gDNA used in this study.
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PMID:Mitochondrial gene therapy augments mitochondrial physiology in a Parkinson's disease cell model. 1937 90