Alternative Drug Delivery in the Treatment of Parkinson’s Disease

Parkinson’s disease is one of the most severe progressive neurodegenerative disorders, having a mortifying effect on the health of millions of people around the globe. The neural cells producing dopamine in the substantia nigra of the brain die out. This leads to symptoms like hypokinesia, rigidity, bradykinesia, and rest tremor. Parkinsonism cannot be cured, but the symptoms can be reduced with the intervention of medicinal drugs, surgical treatments, and physical therapies. Delivering drugs to the brain for treating Parkinson’s disease is very challenging. The blood-brain barrier acts as a highly selective semi-permeable barrier, which refrains the drug from reaching the brain. Conventional drug delivery systems used for Parkinson’s disease do not readily cross the blood barrier and further lead to several side-effects. Recent advancements in drug delivery technologies have facilitated drug delivery to the brain without flooding the bloodstream and by directly targeting the neurons. In the era of Nanotherapeutics, liposomes are an efficient drug delivery option for brain targeting. Liposomes facilitate the passage of drugs across the blood-brain barrier, enhances the efficacy of the drugs, and minimize the side effects related to it. The review aims at providing a broad updated view of the liposomes, which can be used for targeting Parkinson’s disease.

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Blood-brain barrier opening with focused ultrasound in Parkinson’s disease dementia

Nature Communications ◽

10.1038/s41467-021-21022-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Carmen Gasca-Salas ◽

Beatriz Fernández-Rodríguez ◽

José A. Pineda-Pardo ◽

Rafael Rodríguez-Rojas ◽

Ignacio Obeso ◽

...

Keyword(s):

Parkinson’S Disease ◽

Drug Delivery ◽

Parkinson's Disease ◽

Side Effects ◽

Neurodegenerative Disorders ◽

Focused Ultrasound ◽

Temporal Cortex ◽

Clinical State ◽

Cognitive Improvement ◽

Bbb Opening

AbstractMR-guided focused ultrasound (MRgFUS), in combination with intravenous microbubble administration, has been applied for focal temporary BBB opening in patients with neurodegenerative disorders and brain tumors. MRgFUS could become a therapeutic tool for drug delivery of putative neurorestorative therapies. Treatment for Parkinson’s disease with dementia (PDD) is an important unmet need. We initiated a prospective, single-arm, non-randomized, proof-of-concept, safety and feasibility phase I clinical trial (NCT03608553), which is still in progress. The primary outcomes of the study were to demonstrate the safety, feasibility and reversibility of BBB disruption in PDD, targeting the right parieto-occipito-temporal cortex where cortical pathology is foremost in this clinical state. Changes in β-amyloid burden, brain metabolism after treatments and neuropsychological assessments, were analyzed as exploratory measurements. Five patients were recruited from October 2018 until May 2019, and received two treatment sessions separated by 2–3 weeks. The results are set out in a descriptive manner. Overall, this procedure was feasible and reversible with no serious clinical or radiological side effects. We report BBB opening in the parieto-occipito-temporal junction in 8/10 treatments in 5 patients as demonstrated by gadolinium enhancement. In all cases the procedures were uneventful and no side effects were encountered associated with BBB opening. From pre- to post-treatment, mild cognitive improvement was observed, and no major changes were detected in amyloid or fluorodeoxyglucose PET. MRgFUS-BBB opening in PDD is thus safe, reversible, and can be performed repeatedly. This study provides encouragement for the concept of BBB opening for drug delivery to treat dementia in PD and other neurodegenerative disorders.

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Intraparenchymal Drug Delivery for Parkinson’s Disease

Textbook of Stereotactic and Functional Neurosurgery ◽

10.1007/978-3-540-69960-6_103 ◽

2009 ◽

pp. 1731-1742 ◽

Cited By ~ 1

Author(s):

R. D. Penn ◽

A. A. Linninger

Keyword(s):

Parkinson’S Disease ◽

Drug Delivery ◽

Parkinson's Disease

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Selected natural and synthetic agents effective against Parkinson’s disease with diverse mechanisms

Current Topics in Medicinal Chemistry ◽

10.2174/1568026621666211129141316 ◽

2021 ◽

Vol 21 ◽

Author(s):

Hayrettin Ozan Gulcan

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Treatment Options ◽

Treatment Strategies ◽

Current Treatment ◽

Dopamine Metabolism ◽

Dopaminergic Agonists ◽

Alternative Drug ◽

Synthetic Agents ◽

Disease Modifying

: Similar to other neurodegenerative diseases, Parkinson’s disease (PD) has been extensively investigated with respect to its neuropathological background and possible treatment options. Since the symptomatic outcomes are generally related to dopamine deficiency, the current treatment strategies towards PD mainly employ dopaminergic agonists as well as the compounds acting on dopamine metabolism. These drugs do not provide disease modifying properties; therefore alternative drug discovery studies focus on targets involved in the progressive neurodegenerative character of PD. This study has aimed to present the pathophysiology of PD concomitant to the representation of drugs and promising molecules displaying activity against the validated and non-validated targets of PD.

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