Acupuncture Treatment for Parkinson’s Disease: From Clinical Efficacy to Biomarker Discovery

1. Acupuncture treatment in patients with PD

The clinical application of acupuncture treatment for PD began in the early 1970s, when Dr. Li applied Chinese herbal drugs, acupuncture, and moxibustion. The effectiveness and efficacy of the PD drug Madopar (levodopa 50 mg and benserazide 12.5 mg, 3 to 4 times per day) alone or combining with acupuncture were reviewed by Dr. Li’s team (RCTs n = 11, patients n = 831) and indicated that the combination may improve clinical efficacy [5]. In 2008, a study by Ren showed that acupuncture combined with Madopar significantly improved treatment outcomes and reduced the dose of the drug in a study involving 50 patients with PD [6].

Based on prior research, functional magnetic resonance imaging (fMRI) signals were measured during acupuncture at the GB34 acupoint (Yanglingquan) in patients with PD. As a result, significant changes in brain signals were observed in areas commonly impacted by PD, including the substantia nigra, caudate, thalamus, and putamen [7]. In a study conducted by Yeo et al [8], after 8 weeks of acupuncture treatment at various acupoints, including GB34, which is known to be effective in the treatment of PD [9], the total unified Parkinson’s disease rating scale (UPDRS) score, indicating the severity of PD (clinician-scored and monitored), decreased from 18 points to 9 points. This improvement was sustained during an 8-week nontreatment observation period. Other individual scores, including the UPDRS 3 motor function evaluation score, were significantly reduced by acupuncture treatment and remained low during the observation period [8]. Examination of changes in brain signals induced by acupuncture, measured by fMRI in these patients, revealed changes in signals within regions associated with PD [8]. In particular, patients with significantly lower thalamic signals showed a marked increase after acupuncture treatment compared with baseline levels, and a positive correlation was observed between their fMRI signals in the thalamus and UPDRS 3 scores [8]. Given that the thalamus is a crucial brain region for transmitting sensory and motor signals, it can be inferred that acupuncture regulates the thalamic motor nuclei, thus controlling abnormalities in the motor system in PD. Since these results were observed 8 weeks after starting acupuncture treatment, extending the duration of acupuncture could potentially reveal significant signal changes and correlations in other regions of the brain affected by PD (Figure 1).

Figure 1

Research flowchart for acupuncture in PD treatment.

PD = Parkinson’s disease.

2. Acupuncture stimulation in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mouse model

Based on these clinical effects, changes in gene expression regulated by acupuncture were observed in a PD mouse model [10,11]. Among these genes, serum- and glucocorticoid-inducible kinase 1 (Sgk1) was identified as being involved in controlling α-synuclein, a biomarker of PD [12]. Sgk1 has been shown to have diverse cellular functions, including promoting cell survival [13–15]. Sgk1 has been reported to exhibit protective function under oxidative stress conditions [16]. A characteristic feature of neurodegenerative disorders such as PD is oxidative stress [17]. In a PD mouse model induced by MPTP, α-synuclein expression, which was elevated compared with normal mice, was regulated back to normal levels in the group receiving combined acupuncture treatment at GB34 and LR3 with MPTP (hereinafter “acupuncture group”), demonstrating a neuroprotective effect [12]. Furthermore, in the acupuncture group, the expression of Sgk1, which was reduced due to PD, was maintained at normal levels [12]. To examine the correlation between Sgk1 and α-synuclein expression, Sgk1 was knocked out of SH-SY5Y cells (a model for dopaminergic neurons) using small interference RNA targeting Sgk1. Analysis of this model revealed increased expression of α-synuclein and phosphorylated α-synuclein (at y125), both associated with the pathogenesis of PD, in Sgk1-deficient SH-SY5Y cells [12,18]. These findings indicate that changes in Sgk1 gene expression, regulated by acupuncture, are associated with PD pathogenesis. In particular, a decrease in Sgk1 could exacerbate PD, but acupuncture could control this deterioration at the gene expression level, demonstrating a neuroprotective effect.

Among the intensification of research efforts related to the gut-brain axis as a method to identify causes and develop treatments for PD [19,20], gastrointestinal symptoms and changes in α-synuclein expression have been reported to influence the pathogenesis of PD [21,22]. PD mouse model data has revealed that Sgk1 expression, regulated by acupuncture, was markedly reduced in the intestines of the PD-induced group compared with normal mice [23]. A reduction in Sgk1 was associated with an increase in α-synuclein in the intestines [23]. These findings suggest that Sgk1, a PD-related factor that responds to acupuncture, could play a role in the pathogenesis or exacerbation of PD.

Additionally, genes involved in the neuroprotective mechanisms of acupuncture can serve as foundational data to identify treatment targets and uncover the underlying causes of PD. Therefore, the evaluation of acupuncture treatment should go beyond simple efficacy tests. Examining the roles of responsive genes and biomarkers is essential, as it significantly enhances the research value of acupuncture by identifying potential treatment targets and the underlying causes of PD.