A neoteric annotation on the advances in combination therapy for Parkinson’s disease: nanocarrier-based combination approach and future anticipation. Part I: exploring theoretical insights and pharmacological advances

ABSTRACT

Introduction

Parkinson’s disease (PD) is a neurological condition defined by a substantial reduction in dopamine-containing cells in the substantia nigra. Levodopa (L-Dopa) is considered the gold standard in treatment. Recent research has clearly shown that resistance to existing therapies can develop. Moreover, the involvement of multiple pathways in the nigrostriatal dopaminergic neuronal loss suggests that modifying the treatment strategy could effectively reduce this degeneration.

Areas covered

This review summarizes the key concerns with treating PD patients and the combinations, aimed at effectively managing PD. Part I focuses on the clinical diagnosis at every stage of the disease as well as the pharmacological treatment strategies that are applied throughout its course. It methodically elucidates the potency of multifactorial interventions in attenuating the disease trajectory, substantiating the rationale for co-administration of dual or multiple therapeutic agents. Significant emphasis is laid on evidence-based pharmacological combinations for PD management.

Expert opinion

By utilizing multiple drugs in a combination fashion, this approach can leverage the additive or synergistic effects of these agents, amplify the spectrum of treatment, and curtail the risk of side effects by reducing the dose of each drug, demonstrating significantly greater efficacy.

KEYWORDS:

• Parkinson’s disease
• neuronal loss
• multifactorial
• dopamine
• blood-brain barrier
• levodopa
• combinatorial approach

Article highlights

• Multiple pathways involved in nigrostriatal dopaminergic neuronal loss are discussed.

• Current clinical diagnosis and pharmacological treatments for PD, detailing mechanisms of action and therapeutic outcomes have been discussed in detail.

• It provides information about FDA- approved combination therapies, highlighting their roles and benefits in PD treatment.

• Through discussion on the integration of surgical treatment options, such as Deep Brain Stimulation (DBS), in the PD treatment paradigm.

• There is a special focus on the requirement for multifactorial interventions for PD and in-depth analysis of the potential benefits of combining two synthetic molecules, or a synthetic molecule with a phytochemical, in treating PD.

• Focus on synergistic effects of these combinations, emphasizing how their corresponding mechanisms of action contribute to improved treatment outcomes.

• Analysis of recent studies investigating the outcomes of potential drug combinations in the treatment of PD.

• Assessment of the current challenges in PD treatment and the potential of upcoming therapies to address unmet needs in patient care.

This box encapsulates the salient features of the article, providing a concise yet comprehensive overview of the key takeaways.

List of abbreviations

PD	=	Parkinson’s Disease
SNc	=	Substantia nigra pars compacta
CNS	=	Central nervous system
LBs	=	Lewy bodies
Parkin	=	Parkinson juvenile disease protein 2
LRRK2	=	Leucine-rich repeat kinase 2
PINK1	=	PTEN-induced kinase 1
DJ1 or PARK7	=	Parkinsonism-associated deglycase protein
DAT	=	Dopamine active transporter]
DA	=	Dopamine
ROS	=	Reactive oxygen species
MPTP	=	1-methyl-4-phenyl-2,3,6-tetrahydropyridine
DBS	=	Deep brain stimulation
MAO-B	=	Monoamine oxidase type B
COMT	=	Catechol-O-methyl transferase
L-Dopa	=	Levodopa
BBB	=	Blood-brain barrier
6-OHDA	=	6-hydroxydopamine
RES	=	Resveratrol
EGCG	=	Epigallocatechin-3-gallate
TNF	=	Tumor necrosis factor
3-OMD	=	3-Ortho-methyl-dopa
NAD	=	Dinucleotide
CA	=	Caffeic acid
QOL	=	Quality of life

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors would like to acknowledge the UGC, for providing the Savitribai Jyotirao Phule Fellowship for Single Girl Child (SJSGC) fellowship to the first author [Registration ID: UGCES-22-GE-MAD-F-SJSGC-2090]. The authors would also like to acknowledge the funding from DST FIST program to the Department of Pharmaceutics, School of Pharmaceutical Education and Research (SPER), Jamia Hamdard, New Delhi-110062.