The Parkinson's-Reversing Breakthrough

Alternative Treatment for Parkinsons

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Approaches to the pharmacotherapy of the "atypical" parkinsonian or "Parkinson plus" disorders have, as yet, met with little success. Drugs attempting to replace or mimic specific neurotransmitters are relatively ineffective, as evidenced, for example, by the inconsistent response rates to dopamine (DA) replacement by the administration of levodopa. This variable and modest efficacy contrasts with the predictable and significant benefit obtained with dopaminomimetics in Parkinson's disease (PD); in this case, core symptoms arise from the loss of a single transmitter system. By contrast, clinical disability in the atypical parkinsonian disorders reflects more diffuse neuronal damage and multiple neurotransmitter involvement. Nigral dopaminergic neurons degenerate, but so do serotonergic, noradrenergic, and cholinergic neurons. Replacing DA thus can improve parkinsonian rigidity and bradykinesia, but the overall benefit is poor and generally disappears with disease progression. Studies of drugs targeting cholinergic and other monoaminergic systems have usually reported disappointing results. On the other hand, there is a paucity of well-controlled trials of single transmitter replacement strategies, and clinical studies that systematically address multiple system deficiencies are virtually unknown. Indeed, whether a transmitter replacement strategy can be effective in the symptomatic treatment of the Parkinson plus disorders remains uncertain. However, current neurosciences research is providing rapidly increasing insight into the pathogenesis of PD and atypical parkinsonian disorders. With this new understanding comes the possibility of discovering interventions that will slow or stop disease progression. Progress in the search for radiologic and biochemical surrogate markers promises not only earlier and more definitive diagnosis but also efficient and more reliable therapeutic trials.

For the purpose of this review, the atypical parkinsonian disorders have been categorized as follows: (a) multiple system atrophy (MSA), further grouped into MSA-C, previously called olivopontocerebellar atrophy, OPCA; MSA-A, previously called Shy-Drager, SD; MSA-P, previously called striatonigral degeneration SND; (b) progressive supranuclear palsy (PSP); (c) corticobasal degeneration (CBD); and (d) dementia with lewy bodies (DLB). An initial analysis of current therapeutic approaches, based on clinical trial results published since 1980 and organized by the major neu-rotransmitter system targeted, will be followed by consideration of possible directions for future therapeutic research.

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