EFFECT OF L-DOPA ON COURSE OF PARKINSON'S DISEASE

doi:10.1016/S0140-6736(84)90493-8

The Lancet

Volume 324, Issue 8396, 28 July 1984, Pages 211-212

https://doi.org/10.1016/S0140-6736(84)90493-8 Get rights and content

Abstract

A review of the progress of 176 patients with Parkinson's disease who were given maximum tolerated doses of L-dopa between November, 1969, and December, 1972, showed that the ratio of observed to expected deaths after 12 years' sustained therapy was 2·59 (2·14 for males and 3·64 for females). This contrasts with the overall 6-year follow-up figure for the same patients of 1·45 (1·29 for males and 1·85 for females). These findings indicate that although L-dopa may improve life expectancy during the first 6 years of therapy the protective effect subsequently declines.

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Citation Excerpt :
PD progresses through the five stages defined by the Hoehn and Yahr scale [19] and as rated by the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) used in PD diagnosis [20]. PD is an incurable disease, but Levodopa (L-DOPA) therapy raises the life expectancy [21]. L-DOPA is converted into dopamine in the dopaminergic and other neurons containing enzyme Aromatic Amino Acid Decarboxylase (AAAD), also known as DOPA decarboxylase (DDC).
Parkinson's disease (PD) is a common disorder of the central nervous system in the elderly. The pathogenesis of PD is a complex process, with genetics as an important contributing factor. This factor may stem from mitochondrial gene variations and mutations as well as from nuclear gene variations and mutations. More recently, a particular role of mitochondrial dysfunction has been suggested, arising from mitochondrial DNA variations or acquired mutations in PD pathogenesis. The present review summarizes and weighs the evidence in support of mitochondrial DNA (mtDNA) variations as important contributors to the development and course of PD.
Gene therapy approaches for the treatment of Parkinson's disease
2007, Handbook of Clinical Neurology
Levodopa is considered gold-standard treatment by which all other therapies for the long-term treatment of PD patients are compared. Despite being an outstanding therapy, levodopa loses its usefulness because benefit is accompanied by debilitating side-effects that limit its utility. This chapter describes gene therapy approaches for the treatment of Parkinson's disease. When considering a gene therapy strategy to treat any human disease, there are two major unknowns that must be conquered. These are: (1) the safety of the gene transfer itself, and (2) the efficacy of the transgene product. Gene therapies can drive the dose of the therapeutic molecule by placing the vectors in site-specific loci and thus does not affect an unintended brain region that makes delivery of therapeutic genes superior to the delivery of pharmacological agents. For prodopaminergic gene therapy approaches, the postcommissural putamen are regarded the most critical site. Rigorous screening of patients must be conducted before the commencement of gene therapy. Some of the candidates for gene therapy in PD include trophic factors and dopamine-synthesizing enzymes. The transfection of trophic factors offer the greatest benefit, as it can prevent the progressive degeneration of the dopaminergic nigrostriatal system, while enhancing the function of surviving neurons.
Behavioural and immunohistochemical changes following supranigral administration of sonic hedgehog in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets
2002, Neuroscience
Sonic hedgehog (SHH) has trophic actions on dopaminergic cell cultures and protects them from MPP⁺ toxicity but its in vivo actions have not been explored. We now investigate the effects of unilateral supranigral administration of SHH on nigro-striatal function in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets. SHH (0.1 or 1.0 μg) or vehicle was stereotaxically injected into the region of the right substantia nigra twice with an interval of 5 weeks between administrations.
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SHH may improve nigro-striatal function by restoring tyrosine hydroxylase positivity. This is reflected by an improvement in basal disability and a reduction in the lesion-induced response to L-DOPA.
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Occasional SurveyEFFECT OF L-DOPA ON COURSE OF PARKINSON'S DISEASE

Abstract

Parkinsonian onset, progression and mortality

Neurology

Present mortality in Parkinson's disease: the ratio of observed to expected deaths with a method to calculate expected deaths

J Neural Transm

Five years treatment of Parkinson's disease with levodopa-therapeutic results and survival of 100 patients

Ann Intern Med

Evaluation of long-term therapy m Parkinson's disease. Mortality and therapeutic efficacy

Parkinson's disease and levodopa a 5 year follow-up and review

West J Med

Occasional Survey
EFFECT OF L-DOPA ON COURSE OF PARKINSON'S DISEASE