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Continuous Drug Delivery Aiming Continuous Dopaminergic Stimulation in Parkinson's Disease.

ABSTRACT: Continuous dopaminergic stimulation in Parkinson's disease (PD) has several advantages over pulsatile, non-continuous, stimulation. These therapies currently consist of pump-based and transcutaneous therapies and are based on a more constant delivery of the dopaminergic drug resulting in continuous dopaminergic stimulation and a more stable treatment effect. Several clinical and experimental observations have shown that continuous stimulation of dopaminergic receptors induces fewer complications, such as dyskinesia, compared to pulsatile stimulation. Currently available non-oral pharmacological continuous therapies in PD include the transdermal Rotigotine (RTG) patch, infusion therapies with Apomorphine and Intrajejunal Levodopa (IJLI) and the Rivastigmine patch. Here we aim to provide a concise review of these current therapies and discuss ongoing and future developments of continuous non-oral pharmacological dopaminergic therapies in PD.

SUBMITTER: van Wamelen DJ

PROVIDER: S-EPMC6311379 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Continuous Drug Delivery Aiming Continuous Dopaminergic Stimulation in Parkinson's Disease.

van Wamelen Daniel J DJ Grigoriou Sotirios S Chaudhuri K Ray KR Odin Per P

Journal of Parkinson's disease 20180101 s1

Continuous dopaminergic stimulation in Parkinson's disease (PD) has several advantages over pulsatile, non-continuous, stimulation. These therapies currently consist of pump-based and transcutaneous therapies and are based on a more constant delivery of the dopaminergic drug resulting in continuous dopaminergic stimulation and a more stable treatment effect. Several clinical and experimental observations have shown that continuous stimulation of dopaminergic receptors induces fewer complications ...[more]

PMID: 30584160

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Project description:Background:Spinal cord stimulation (SCS) exerts neuroprotective effects in animal models of Parkinson's disease (PD). Conventional stimulation techniques entail limited stimulation time and restricted movement of animals, warranting the need for optimizing the SCS regimen to address the progressive nature of the disease and to improve its clinical translation to PD patients. Objective:Recognizing the limitations of conventional stimulation, we now investigated the effects of continuous SCS in freely moving parkinsonian rats. Methods:We developed a small device that could deliver continuous SCS. At the start of the experiment, thirty female Sprague-Dawley rats received the dopamine (DA)-depleting neurotoxin, 6-hydroxydopamine, into the right striatum. The SCS device was fixed below the shoulder area of the back of the animal, and a line from this device was passed under the skin to an electrode that was then implanted epidurally over the dorsal column. The rats were divided into three groups: control, 8-h stimulation, and 24-h stimulation, and behaviorally tested then euthanized for immunohistochemical analysis. Results:The 8- and 24-h stimulation groups displayed significant behavioral improvement compared to the control group. Both SCS-stimulated groups exhibited significantly preserved tyrosine hydroxylase (TH)-positive fibers and neurons in the striatum and substantia nigra pars compacta (SNc), respectively, compared to the control group. Notably, the 24-h stimulation group showed significantly pronounced preservation of the striatal TH-positive fibers compared to the 8-h stimulation group. Moreover, the 24-h group demonstrated significantly reduced number of microglia in the striatum and SNc and increased laminin-positive area of the cerebral cortex compared to the control group. Conclusions:This study demonstrated the behavioral and histological benefits of continuous SCS in a time-dependent manner in freely moving PD animals, possibly mediated by anti-inflammatory and angiogenic mechanisms.

Dataset Information

Continuous Drug Delivery Aiming Continuous Dopaminergic Stimulation in Parkinson's Disease.

Publications

Continuous Drug Delivery Aiming Continuous Dopaminergic Stimulation in Parkinson's Disease.

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