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Innovations in Parkinson’s Disease

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Dr. Sneha Mantri

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Guest Editor

1. Department of Neurology, Duke University School of Medicine, 932 Morreene Rd, Box 3333, Durham, NC 27705 USA
2. Parkinson’s Foundation,1359 Broadway, Ste 1509, New York, NY 10018, USA
Interests: Parkinson’s disease; movement disorders; chronic neurodegenerative conditions; integrative medicine; health systems science; narrative medicine

Special Issue Information

Dear Colleagues,

Parkinson’s disease (PD) is the fastest-growing neurodegenerative disease in the world. By 2050, an estimated 25 million individuals will be affected, an increase of more than 100% since 2020. The rapid rise in both incidence and prevalence of PD will require novel and innovative approaches to identification, treatment, and prevention.

This Special Issue will highlight research studies, articles, and reviews that address the unmet needs of people with PD. Articles on any of the following topics, identified by the National Roundtable on Parkinson’s Disease, are welcome:

Diagnostic Advances;
Therapeutic Innovations;
Patient Perspectives;
Disease Prevention;
Home-Based Medical Care;
Clininical Care Team Dynamics;
Clinical Value-Based Care.

Scalable innovations will receive special attention.

Dr. Sneha Mantri
Guest Editor

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19 pages, 1724 KB

Open AccessArticle

Speech Impairment in Early Parkinson’s Disease Is Associated with Nigrostriatal Dopaminergic Dysfunction

by Sotirios Polychronis, Grigorios Nasios, Efthimios Dardiotis, Rayo Akande and Gennaro Pagano

J. Clin. Med. 2026, 15(3), 1006; https://doi.org/10.3390/jcm15031006 - 27 Jan 2026

Abstract

Background/Objectives: Speech difficulties are an early and disabling manifestation of Parkinson’s disease (PD), affecting communication and quality of life. This study aimed to examine demographic, clinical, dopaminergic imaging and cerebrospinal fluid (CSF) correlates of speech difficulties in early PD, comparing treatment-naïve and levodopa-treated patients. Methods: A cross-sectional analysis was conducted using data from the Parkinson’s Progression Markers Initiative (PPMI). The sample included 376 treatment-naïve and 133 levodopa-treated early PD participants. Speech difficulties were defined by Movement Disorder Society—Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III, with Item 3.1 ≥ 1. Group comparisons and binary logistic regression identified predictors among demographic, clinical, dopaminergic and CSF biomarker variables, including [¹²³I]FP-CIT specific binding ratios (SBRs). All analyses were cross-sectional, and findings reflect associative relationships rather than treatment effects or causal mechanisms. Results: Speech difficulties were present in 44% of treatment-naïve and 57% of levodopa-treated participants. In both cohorts, higher MDS-UPDRS Part III ON scores—reflecting greater motor severity—and lower mean putamen SBR values were significant independent predictors of speech impairment. Age was an additional predictor in the treatment-naïve group. No significant differences were found in CSF biomarkers (α-synuclein, amyloid-β, tau, phosphorylated tau). These findings indicate that striatal dopaminergic loss, particularly in the putamen, and motor dysfunction relate to early PD-related speech difficulties, whereas CSF neurodegeneration markers do not differentiate affected patients. Conclusions: Speech difficulties in early PD are primarily linked to dopaminergic and motor dysfunction rather than global neurodegenerative biomarker changes. Longitudinal and multimodal studies integrating acoustic, neuroimaging, and cognitive measures are warranted to elucidate the neural basis of speech decline and inform targeted interventions. Full article

(This article belongs to the Special Issue Innovations in Parkinson’s Disease)

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20 pages, 3051 KB

Open AccessArticle

Five-Year Follow-Up of Photobiomodulation in Parkinson’s Disease: A Case Series Exploring Clinical Stability and Microbiome Modulation

by Brian Bicknell, Ann Liebert, Craig McLachlan and Hosen Kiat

J. Clin. Med. 2026, 15(1), 368; https://doi.org/10.3390/jcm15010368 - 4 Jan 2026

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Abstract

Background: Parkinson’s disease (PD) involves progressive neurodegeneration with clinical or subclinical disturbance of the gut–brain axis, including altered gastrointestinal motility and enteric nervous system involvement. Clinical studies have reported gut microbiome alterations in PD, with shifts in taxa associated with inflammatory signalling and short-chain fatty acid (SCFA) metabolism. Photobiomodulation (PBM), a non-invasive light therapy, has been investigated as a potential adjunctive treatment for PD, with proposed effects on neural, metabolic, and immune pathways. We previously reported the five-year clinical outcomes in a PBM-treated Parkinson’s disease case series. Here we report the five-year gut microbiome outcomes based on longitudinal samples collected from the same participants. This was an exploratory, open-label longitudinal study without a control group. Objective: Our objective was to assess whether long-term PBM was associated with changes in gut microbiome diversity and composition in the same Parkinson’s disease cohort as previously assessed for changes in Parkinson’s symptoms. Methods: Six participants from the earlier PBM proof-of-concept study who had been diagnosed with idiopathic PD and who had continued treatment (transcranial light emitting diode [LED] plus abdominal and neck laser) for five years had their faecal samples analysed by 16S rDNA sequencing to assess microbiome diversity and taxonomic composition. Results: Microbiome analysis revealed significantly reduced evenness (α-diversity) and significant shifts in β-diversity over five years, as assessed by Permutational Multivariate Analysis of Variance (PERMANOVA). At the phylum level, Pseudomonadota and Methanobacteriota decreased in four of the six participants. Both of these phyla are often increased in the Parkinson’s microbiome compared with the microbiomes of healthy controls. Family-level changes included increased acetate-producing Bifidobacteriaceae (five of the six participants); decreased pro-inflammatory, lipopolysaccharide (LPS)-producing Enterobacteriaceae (two of the three participants who have this bacterial family present); and decreased LPS- and H₂S-producing Desulfovibrionaceae (five of six). At the genus level, Faecalibacterium, a key butyrate producer, increased in four of the six participants, potentially leading to more SCFA availability, although other SCFA-producing bacteria were decreased. This was accompanied by reductions in pro-inflammatory LPS and H₂S-producing genera that are often increased in the Parkinson’s microbiome. Conclusions: This five-year case series represents the longest follow-up of microbiome changes in Parkinson’s disease, although the interpretation of results is limited by very small numbers, the lack of a control group, and the inability to control for lifestyle influences such as dietary changes. While causal relationships cannot be inferred, the parallel changes in improvements in mobility and non-motor Parkinson’s symptoms observed in this cohort, raises the hypothesis that PBM may interact with the gut–brain axis via the microbiome. Controlled studies incorporating functional multi-omics are needed to clarify potential mechanistic links between microbial function, host metabolism, and clinical outcomes. Full article

(This article belongs to the Special Issue Innovations in Parkinson’s Disease)

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