Intraventricular dopamine infusion alleviates motor symptoms in a primate model of Parkinson's disease

Moreau, Caroline; Rolland, Anne Sophie; Pioli, Elsa Y.; Li, Qin; Odou, Pascal; Barthélémy, Christine; Lannoy, Damien; Demailly, A.; Carta, Natacha; Deramecourt, Vincent; Auger, F.; Kuchcinski, Grégory; Laloux, Charlotte; Defebvre, Luc; Bordet, Régis; Duce, James A.; Devedjian, Jean Christophe; Bézard, Erwan; Fisichella, Matthieu; Devos, David

doi:10.1016/j.nbd.2020.104846

Cited by 13 publications

(10 citation statements)

References 20 publications

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“…136 This approach is currently considered for dopamine administration. 137,138 With such procedures, high local concentrations of drugs and personalized concentrations can be achieved with minimal or no systemic adverse effects. This strategy can be also combined with NPs.…”

Section: Intrathecal Intracerebroventricular and Intraparenchymal Adm...mentioning

confidence: 99%

Enhancing paracellular and transcellular permeability using nanotechnological approaches for the treatment of brain and retinal diseases

Khalil,

Barras,

Boukherroub

et al. 2024

Nanoscale Horiz.

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Section: Intrathecal Intracerebroventricular and Intraparenchymal Adm...mentioning

confidence: 99%

Enhancing paracellular and transcellular permeability using nanotechnological approaches for the treatment of brain and retinal diseases

Khalil,

Barras,

Boukherroub

et al. 2024

Nanoscale Horiz.

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“…The most astounding preclinical finding was that even at very high doses of dopamine, no dyskinesia was observed in any of the three models. Conversely, oral L-DOPA induced dyskinesia even with the smallest effective dose [51,52]. A Phase I/IIB clinical trial involving 12 patients is in progress (ClinicalTrials.gov ID: NCT04332276) [53].…”

Section: How Can Continuous Dopaminergic Delivery Therapies Be Improved?mentioning

confidence: 99%

“…Conversely, oral L-DOPA induced dyskinesia even with the smallest effective dose [51,52]. A Phase I/IIB clinical trial involving 12 patients is in progress (ClinicalTrials.gov ID: NCT04332276) [53]. Although clinical data and further Pk analysis are required, it is consistent to hypothesize that central administration of A-dopamine could limit peripheral and central Pk problems and Pd issues (i.e., pulsatile stimulation and dopamine misdistribution).…”

Section: How Can Continuous Dopaminergic Delivery Therapies Be Improved?mentioning

confidence: 99%

Effectiveness of Continuous Dopaminergic Therapies in Parkinson’s Disease: A Review of L-DOPA Pharmacokinetics/Pharmacodynamics

Demailly,

Moreau,

Devos

2024

Journal of Parkinson’s Disease

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Background: Parkinson’s disease (PD) is characterized by striatal dopamine deficiency. Since dopamine cannot cross the digestive and blood-brain barriers, its precursor, levodopa (L-DOPA), remains the mainstay of treatment. However, the significant pharmacokinetic (Pk) and pharmacodynamic (Pd) limitations of L-DOPA, combined with the severity of PD, may trigger motor and non-motor complications, for which continuous dopaminergic delivery therapies have been developed. Objective: The aim of this study was to review the literature on the Pk/Pd limitations of L-DOPA and how current treatments of continuous dopaminergic administration ameliorate these problems, in order to identify the need for new therapeutic avenues. Methods: A comprehensive literature search was carried out using PubMed and 75 articles were initially extracted. Following independent screening by two reviewers and consideration of eligibility, 10 articles were chosen for further analysis. Information concerning the Pk/Pd of L-DOPA was classified for each article. Results: Pk/Pd problems notably include: (i) restricted digestive and cerebral absorption; (ii) unnecessary peripheral distribution; (iii) short half-life; (iv) age- and PD-induced decline of central aromatic L-amino acid decarboxylase; (v) misdistribution in many cells; and (vii) pulsatile stimulation of dopaminergic receptors. Current treatments only slightly ameliorate some of these problems. Conclusions: Many Pk/Pd constraints are not resolved by existing continuous dopaminergic delivery therapies. This highlights the significant gap between these treatments and the ideal of continuous dopaminergic stimulation.

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“…Intracranial or intracerebroventricular administrations are the best options currently available to ensure precise control of the dose of product administered to the brain. However, this mode of delivery is invasive and requests the implantation of a device allowing continuous or intermittent delivery [ 267 ]. Such procedure would be possibly attractive to patients with the most advanced cases or short pejorative outcomes, e.g., patients with amyotrophic lateral sclerosis or advanced stages of Alzheimer’s or Parkinson’s diseases, pending associated surgery remains possible.…”

Section: Platelet Lysates For Brain Administration: Pending Questionsmentioning

confidence: 99%

Can the administration of platelet lysates to the brain help treat neurological disorders?

Nebie

Buée

Blum

et al. 2022

Cell. Mol. Life Sci.

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Neurodegenerative disorders of the central nervous system (CNS) and brain traumatic insults are characterized by complex overlapping pathophysiological alterations encompassing neuroinflammation, alterations of synaptic functions, oxidative stress, and progressive neurodegeneration that eventually lead to irreversible motor and cognitive dysfunctions. A single pharmacological approach is unlikely to provide a complementary set of molecular therapeutic actions suitable to resolve these complex pathologies. Recent preclinical data are providing evidence-based scientific rationales to support biotherapies based on administering neurotrophic factors and extracellular vesicles present in the lysates of human platelets collected from healthy donors to the brain. Here, we present the most recent findings on the composition of the platelet proteome that can activate complementary signaling pathways in vivo to trigger neuroprotection, synapse protection, anti-inflammation, antioxidation, and neurorestoration. We also report experimental data where the administration of human platelet lysates (HPL) was safe and resulted in beneficial neuroprotective effects in established rodent models of neurodegenerative diseases such as Parkinson’s disease, Alzheimer's disease, traumatic brain injury, and stroke. Platelet-based biotherapies, prepared from collected platelet concentrates (PC), are emerging as a novel pragmatic and accessible translational therapeutic strategy for treating neurological diseases. Based on this assumption, we further elaborated on various clinical, manufacturing, and regulatory issues that need to be addressed to ensure the ethical supply, quality, and safety of HPL preparations for treating neurodegenerative and traumatic pathologies of the CNS. HPL made from PC may become a unique approach for scientifically based treatments of neurological disorders readily accessible in low-, middle-, and high-income countries. Graphical abstract

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Intraventricular dopamine infusion alleviates motor symptoms in a primate model of Parkinson's disease

Cited by 13 publications

References 20 publications

Enhancing paracellular and transcellular permeability using nanotechnological approaches for the treatment of brain and retinal diseases

Enhancing paracellular and transcellular permeability using nanotechnological approaches for the treatment of brain and retinal diseases

Effectiveness of Continuous Dopaminergic Therapies in Parkinson’s Disease: A Review of L-DOPA Pharmacokinetics/Pharmacodynamics

Can the administration of platelet lysates to the brain help treat neurological disorders?

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