Immunotherapies for Parkinson’s Disease: Progression of Clinical Development

Teng, Jet Shee; Ooi, Yin Yin; Chye, Soi Moi; Ling, Anna Pick Kiong; Koh, Rhun Yian

doi:10.2174/1871527320666210526160926

Cited by 7 publications

(6 citation statements)

References 90 publications

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“…Another promising approach is to promote the clearance of and prevent the cellular spread of α-synuclein through immunotherapy [ 120 ]. There are several agents currently under study, including Cinpanemab and Prasinezumab, which are both used in passive immunotherapy.…”

Section: Resultsmentioning

confidence: 99%

Current Treatments and New, Tentative Therapies for Parkinson’s Disease

Pardo-Moreno¹,

García‐Morales

Suleiman‐Martos

et al. 2023

Pharmaceutics

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Parkinson’s disease (PD) is a neurodegenerative pathology, the origin of which is associated with the death of neuronal cells involved in the production of dopamine. The prevalence of PD has increased exponentially. The aim of this review was to describe the novel treatments for PD that are currently under investigation and study and the possible therapeutic targets. The pathophysiology of this disease is based on the formation of alpha-synuclein folds that generate Lewy bodies, which are cytotoxic and reduce dopamine levels. Most pharmacological treatments for PD target alpha-synuclein to reduce the symptoms. These include treatments aimed at reducing the accumulation of alpha-synuclein (epigallocatechin), reducing its clearance via immunotherapy, inhibiting LRRK2, and upregulating cerebrosidase (ambroxol). Parkinson’s disease continues to be a pathology of unknown origin that generates a significant social cost for the patients who suffer from it. Although there is still no definitive cure for this disease at present, there are numerous treatments available aimed at reducing the symptomatology of PD in addition to other therapeutic alternatives that are still under investigation. However, the therapeutic approach to this pathology should include a combination of pharmacological and non-pharmacological strategies to maximise outcomes and improve symptomatological control in these patients. It is therefore necessary to delve deeper into the pathophysiology of the disease in order to improve these treatments and therefore the quality of life of the patients.

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Section: Resultsmentioning

confidence: 99%

Current Treatments and New, Tentative Therapies for Parkinson’s Disease

Pardo-Moreno¹,

García‐Morales

Suleiman‐Martos

et al. 2023

Pharmaceutics

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“…Following selection, a nanobody, PFFNB2, was identified that could not inhibit the aggregation of αSyn monomer, though it can specifically recognize and significantly dissociate αSyn fibrils. A series of humanized monoclonal antibodies BIIB054 (cinpanemab), MEDI1341, AFFITOPE, and PRX002 (prasinezumab) were under clinical development [ 422 ]. However, despite the huge financial costs, the results of these developments were rather discouraging.…”

Section: Treatment and Optimization Of The Condition Of Patients With Pdmentioning

confidence: 99%

Molecular and Cellular Interactions in Pathogenesis of Sporadic Parkinson Disease

Dolgacheva

Зинченко

Гончаров

2022

IJMS

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An increasing number of the population all around the world suffer from age-associated neurodegenerative diseases including Parkinson’s disease (PD). This disorder presents different signs of genetic, epigenetic and environmental origin, and molecular, cellular and intracellular dysfunction. At the molecular level, α-synuclein (αSyn) was identified as the principal molecule constituting the Lewy bodies (LB). The gut microbiota participates in the pathogenesis of PD and may contribute to the loss of dopaminergic neurons through mitochondrial dysfunction. The most important pathogenetic link is an imbalance of Ca2+ ions, which is associated with redox imbalance in the cells and increased generation of reactive oxygen species (ROS). In this review, genetic, epigenetic and environmental factors that cause these disorders and their cause-and-effect relationships are considered. As a constituent of environmental factors, the example of organophosphates (OPs) is also reviewed. The role of endothelial damage in the pathogenesis of PD is discussed, and a ‘triple hit hypothesis’ is proposed as a modification of Braak’s dual hit one. In the absence of effective therapies for neurodegenerative diseases, more and more evidence is emerging about the positive impact of nutritional structure and healthy lifestyle on the state of blood vessels and the risk of developing these diseases.

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“…They reported the pharmacokinetics, safety and tolerability in phase I, prasinezumab did not show relevant clinical benefits according to MDS-UPDRS outcomes. [98][99][100][101] Inhibition of RGMa: The Future Concept?…”

Section: Current Ongoing Disease Modifying Interventions In Pdmentioning

confidence: 99%

View Point: Disease Modification and Cell Secretome Based Approaches in Parkinson’s Disease: Are We on the Right Track?

Müller¹

2021

BTT

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The term idiopathic Parkinson’s disease describes an entity of various not well-characterized disorders resembling each other. They are characterized by chronic neuronal dying originating from various disease mechanisms. They result in the onset of motor and related non-motor features, both of which respond to administration of personalized drug combinations and surgical therapies. The unmet need is beneficial disease course modification with repair and neurogenesis. Objectives are to discuss the value of cell secretome based treatments including neuronal graft transplantation and to suggest as an alternative the stimulation of an endogenous available approach for neuronal repair. Chronic neurodegenerative processes result from different heterogeneous, but complementing metabolic, pathological cascade sequences. Accumulated evidence from experimental research suggested neuron transplantation, stem cell application and cell secretome-based therapies as a promising future treatment with cure as an ultimate goal. To date, clinical testing of disease-modifying treatments has focused on substitution or repair of the remaining dopamine synthesizing neurons following diagnosis. At diagnosis, many of the still surviving and functioning, but already affected neurons have lost most of their axons and are primed for cell death. A more promising therapeutic concept may be the stimulation of an existing, endogenous repair system in the peripheral and central nervous systems. The abundant protein repulsive guidance molecule A blocks restoration and neurogenesis, both of which are mediated via the neogenin receptor. Inhibition of the physiological effects of repulsive guidance molecule A is an endogenous available repair pathway in chronic neurodegeneration. Antagonism of this protein with antibodies or stimulation of the neogenin receptor should be considered as an initial repair step. It is an alternative to cell replacement, stem cell or associated cell secretome concepts.

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Immunotherapies for Parkinson’s Disease: Progression of Clinical Development

Cited by 7 publications

References 90 publications

Current Treatments and New, Tentative Therapies for Parkinson’s Disease

Current Treatments and New, Tentative Therapies for Parkinson’s Disease

Molecular and Cellular Interactions in Pathogenesis of Sporadic Parkinson Disease

View Point: Disease Modification and Cell Secretome Based Approaches in Parkinson’s Disease: Are We on the Right Track?

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