Hope in Motion: Clinical Progress and Social Support for Parkinson’s

Parkinson’s disease (PD) remains an incurable neurological disorder that disproportionately affects the aging population, profoundly impacting patients and their families. In pursuit of better management strategies, extensive research and clinical trials are underway. Many of these efforts have yielded promising breakthroughs that offer hope for improving quality of life, despite the limited understanding of PD’s underlying aetiology.

This article highlights recent advances in PD management, including novel therapeutic approaches such as α-synuclein–targeted treatments, induced pluripotent stem cell replacement therapy, drug repurposing, deep brain stimulation, and non-pharmacological interventions. While much of this research is still in progress, these developments provide an encouraging outlook for the future of PD treatment and underscore the need for sustained, large-scale, and rigorous investigation to move beyond the current status quo.

Introduction

Parkinson’s Disease (PD) is a progressively deteriorating neurological disorder. PD most commonly affects populations over the age of 60, while it is comparatively less prevalent in younger populations.1,2 The disease is characterised by motor symptoms such as tremors, bradykinesia, poor balance and posture, speech changes, muscle stiffness; and non-motor symptoms such as depression, anxiety, and sleep disturbance, among others.1-3 In 2021 the prevalent cases of PD reached 11,767,271.97, suggesting a 2.74-fold increase in the number of cases compared to that in 1990.4 The situation is even more dire in China: the estimated prevalence rose from 66.3 per 100,000 people in 1990 to 240.8 in 2023 (Figure 1).5 Symptoms of PD are caused by a loss of dopaminergic neurons, primarily in the substantia nigra pars compacta.2,6 A number of mechanisms have been proposed for the pathogenesis of PD, ranging from the formation of misfolded α-synuclein and protein aggregation, malfunctions in the protein clearance system, to dysfunctional mitochondria.6 Despite extensive efforts to elucidate its underlying causes, the aetiology of PD remains unclear. Nevertheless, these ongoing research efforts have led to significant recent advances in its management.

Treatments Targeting α-Synuclein

As aforementioned, α-synuclein is critical in PD development. Encoded by the SNCA gene, α-synuclein exists natively as an aqueous-soluble, unfolded protein without a rigid tertiary conformation.6,7 The natively unfolded α-synuclein monomer undergoes a significant structural transition to an α-helical conformation upon interacting with negatively charged lipids or pre-existing β-sheet-rich structures (such as oligomers or fibrils).6,7 The aggregation of α-synuclein monomers into protofibrils and oligomers is a critical step in the pathogenesis of PD.7 These prefibrillar intermediates are considered highly neurotoxic, causing cellular dysfunction before eventually maturing into insoluble fibrils that make up Lewy bodies (LB).7 LBs are central to both PD and Lewy body dementia, and they can also overlap with Alzheimer's disease (AD).8 Therefore, targeting and reducing α-synuclein formation is the most heavily pursued disease-modifying strategy in PD.9

Reducing α-Synuclein

Recent research targeting α-synuclein has demonstrated potential disease-modifying effects. One such example is buntanetap, which acts by reducing α-synuclein production in neurons.9 Buntanetap is a small molecule that blocks the translation of mRNAs into proteins (including α-synuclein) specifically in diseased cells.10 In a study involving 53 patients with early PD and 14 patients with AD over a 25 ± 2 day period, Fang et al. demonstrated that buntanetap’s rapid effects support its potential as a symptomatic treatment, while also hypothesising that it may possess long-term disease-modifying properties for PD.10 However, the treatment effect is only nominally significant.11 Currently, a phase III trial is underway to ascertain buntanetap’s long-term effects (NCT06709014).11

Preventing α-Synuclein Propagation

Another example of an α‑synuclein–targeting therapy is prasinezumab, the first monoclonal antibody designed to bind α‑synuclein aggregates and inhibit their intercellular propagation.12 Although in the PASADENA phase 2 study, prasinezumab did not demonstrate significant effects in Parts I and II of the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS‑UPDRS), it was associated with a slowing of motor function decline in Part III.12 An exploratory analysis of PASADENA might suggest that prasinezumab slows the progression of motor signs in individuals with characteristics usually associated with more rapid progression within a 1-year timeframe.12 To this end, PADOVA, a larger-scaled clinical trial, is underway (NCT04777331).13,14

Targeting α-Synuclein with Vaccines

A proposed way to neutralise α-synuclein is through immunotherapy. PD01A and PD03A vaccines represent the first active immunotherapies developed to target the C‑terminal region of the α‑synuclein protein.15,16 To produce the vaccines, the antigenic peptides PD01 and PD03 are conjugated to keyhole limpet hemocyanin and adsorbed onto aluminium hydroxide.15,16 These vaccine designs utilise antigenic B-cell epitopes to stimulate the production of anti-α-synuclein antibodies, while relying on the conjugated carrier protein to provide foreign helper T-cell epitopes for sustained antibody production without triggering auto-reactive T-cell responses15,16 In both phase I studies, the vaccines were safe and well-tolerated, with significant humoral immunity against α-synuclein (n=21 for PD01A; n=36 for PD03A).15,16 The immunogenicity of PD01A was higher than that of PD03A.16 However, the therapeutic efficacies of these vaccines have not been studied and are the central focus of coming phase II research.15,16

Figure 1. Estimated worldwide Parkinson’s Disease prevalence 2023 (per 100,000 people)5

Induced Pluripotent Stem Cell Therapy for PD

As is well known, PD symptoms primarily originate from the loss of dopaminergic neurons in the substantia nigra pars compacta region. Replenishing dopaminergic neurons has long been pursued as a therapeutic strategy for PD, with efforts dating back as early as 1989.17 Yet, owing to technological limitations and ethical concerns regarding the use of human embryonic stem cells for the said purpose, researching cell replacement therapies for PD has been arduous.17 The advent of induced pluripotent stem cell (iPSC) technology has significantly advanced research into cell replacement therapies for PD.17 Notably, Japan completed a phase I/II clinical trial of iPSC‑derived dopaminergic cells for PD in 2025.18

While iPSCs have facilitated progress in developing cell replacement therapies for PD, the process remains highly complex and challenging. The iPSC cells were obtained from an established master cell bank and were then subjected to neural induction via SMAD inhibition and floor plate induction protocol.19,20 Yet the importance of cell sorting and quality control must be underscored —as the undesirable cells may limit treatment efficacy or even exacerbate dyskinesia, and worse still, form tumours.20 Using Fluorescence-Activated Cell Sorting (FACS) to isolate CORIN+ cells is a well-established strategy to enrich midbrain dopaminergic (mDA) progenitors.20 Following transplantation into hemi-parkinsonian rat models, these sorted populations exhibited robust post-graft survival, integrated functionally into the host striatum, and induced significant, quantifiable improvements in motor behaviour.20 Using the method described above, the iPSC-derived dopaminergic progenitors were prepared for the transplantation in the clinical trial.18

The encouraging results from Sawamoto et al.’s trial demonstrated both the safety and efficacy of cell replacement therapy for PD using iPSC‑derived dopaminergic progenitors. Over the two years following bilateral transplantation in 7 patients (PD01–06, PD08) included in the safety analysis, no serious adverse events were reported. The adverse events that did occur were largely transient and unlikely to be attributable to the transplanted cells. Furthermore, magnetic resonance imaging revealed no evidence of tumour formation or growth. The efficacy of the treatment was further investigated in 6 of the 7 patients, excluding the patient with unilateral transplants performed separately (PD01). The Unified Dyskinesia Rating Scale (UDysRS) total scores improved in 5 of the 6 patients over 24 months, with an average increase of 12.3 points from baseline. As another secondary endpoint, treatment efficacy was assessed using the MDS‑UPDRS Part III. Surprisingly, 4 of the 6 eligible patients demonstrated improved motor function during the off‑time period (more than 12 hours without medication), while 5 of the 6 showed improvement during the on‑time period (with medication). The combined MDS‑UPDRS Parts I + II + III (OFF) revealed a modest average improvement of -3.1 points over 24 months.18 These findings suggest that cell replacement therapy may confer therapeutic benefits in addition to demonstrating a favourable safety profile (Figure 2). As noted in the study, future investigations that are double‑blinded, placebo‑controlled, and conducted with larger sample sizes may address its limitations and provide further benefits to the development of cell replacement therapy.18

Figure 2. Chronological changes in clinical end points.18 MDS-UPDRS: Movement Disorder Society-sponsored revision

of the Unified Parkinson’s Disease Rating Scale; UDysRS: Unified Dyskinesia Rating Scale

Drug Repurposing for PD

Glucagon-like peptide-1receptor (GLP-1R) agonists, widely used in diabetes treatment, may potentially be beneficial to PD treatment. Meta‑analyses and reviews have indicated that treatment with GLP‑1R agonists may enhance both motor and cognitive functions in PD patients.21,22 The neuroprotective effects of GLP-1R agonists such as exendin-4 and liraglutide have been well documented in mouse models.20 In addition to preclinical evidence supporting the benefits of GLP‑1R agonists in PD, clinical trials have also demonstrated that these agents can produce favourable outcomes.21,22 In a meta‑analysis of five eligible studies comprising 484 patients, in the off-medication state, GLP-1R agonists improved the MDS-UPDRS Part III score by -1.22 points compared to placebo (95% confidence interval [CI] -2.46, 0.22; P = 0.05); and in the on-medication state, there was a -2.52 point improvement (95% CI -4.02, −1.01; P = 0.001).22 In addition, cognitive performance, assessed via the Mattis Dementia Rating Scale-2 (MATTIS-DRS2), improved by 1.32 points (95% CI 0.16, 2.52; P = 0.03).22 These improvements may stem from the anti‑inflammatory properties of GLP‑1R agonists, their capacity to reduce oxidative stress and protein misfolding, and their ability to promote autophagy.21 These data showed that GLP-1 receptor agonists improved motor and cognitive performance in PD, suggesting potential symptomatic benefits. However, further studies are needed to evaluate their long-term effects and their role in disease modification.22

Deep Brain Stimulation (DBS)

Deep brain stimulation (DBS) is a highly effective surgical treatment for managing PD, typically considered when medication and other therapeutic options are no longer sufficient. The procedure involves implanting electrodes into specific brain regions—such as the globus pallidus internus (GPi), subthalamic nucleus (STN), and ventral intermediate nucleus (VIM)—which are then connected to a pacemaker‑like device that delivers electrical impulses to modulate neural activity.23,24 Each targeted region serves distinct functions, and stimulation should be tailored to the patient’s individual therapeutic goals.24 Future research on DBS may explore its potential disease‑modifying effects, novel stimulation targets, multi-target approaches, and the integration of artificial intelligence into adaptive DBS systems.25,26

Non-pharmacological Support for PD Patients

Beyond medical advances in PD treatment, equal attention must be given to societal care, non-pharmacological interventions, psychological support, and caregiver assistance. A qualitative collective case study conducted in Northern and Midland regions of England examined the impact of societal care interventions.27 The findings indicated that effective societal care yields a wide range of interconnected benefits—physical, psychological, social, and service-related—as illustrated in Figure 3.27

Figure 3. Benefits of social care.27 GP: general practitioner

Notably, the study highlighted the role of timely, high-quality societal care in mitigating the overall cost burden associated with managing PD.27 Physical non-pharmacological interventions—such as dietary modification and structured exercise—have also demonstrated clear benefits in disease management. In addition to physical improvements, exercise has been shown to enhance cognitive function and mental well-being,28 and to slow the decline in postural control and gait stability among PD patients.29 Dietary patterns, including adherence to a Mediterranean diet, consumption of unprocessed foods, and moderate coffee intake, have similarly been associated with slower disease progression.29 These findings are particularly significant given that pharmacological treatments, despite their widespread use and potential side effects, often have limited impact on maintaining or improving mental health.28 However, the evidence base supporting non-pharmacological interventions remains limited, largely due to challenges inherent in studying lifestyle-based approaches. Furthermore, public awareness of PD continues to be inadequate, as noted in the study by Tod et al.27

In Hong Kong, there are a limited number of organisations that provide support for patients with PD. Notably, the Hong Kong Parkinson’s Disease Foundation offers a range of services to patients and their caregivers, including day care programmes, transportation services, and a personal emergency link service.30 Additionally, a range of resources are available, including information on treatment options, caregiving advice, publications on the foundation’s activities, updates on PD, and recreational programmes such as table tennis competitions and Tai Chi classes.30 The Elderly Health Service under the Department of Health also provides information and guidance on caring for individuals with PD.31

Conclusion

PD is a progressive neurological disorder caused by the loss of dopamine-producing neurons, leading to motor and non-motor symptoms. Although it is currently incurable, recent advances aim to improve management and slow disease progression. New treatments focus on targeting α‑synuclein, a key protein in PD, through drugs, antibodies, and vaccines. Stem cell therapy has also shown promise in replacing damaged neurons, while diabetes drugs (GLP‑1 agonists) may improve symptoms. Deep brain stimulation remains an effective option for advanced cases. In addition, lifestyle changes, exercise, and social support are important in improving patients’ quality of life. Overall, these developments offer hope for better treatment and future breakthroughs.

References

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