Parkinson’s Disease Medication Monitored with Fingertip Sweat Patch

Engineers and neuroscientists at the University of California (UC) San Diego have developed a soft, wearable fingertip patch that continuously tracks a Parkinson’s disease (PD) patient’s levodopa medication levels by measuring chemicals in their sweat, with no batteries required. Tests in healthy volunteers and in Parkinson’s disease patients showed that measurements generated using the device were comparable to those obtained by standard laboratory blood tests.

The wearable device offers a way to continuously track real-time concentrations of levodopa in the body and could enable doctors to precisely customize daily medication schedules for patients at home.

The research was led by Tamoghna Saha, PhD, a postdoctoral researcher in the lab of Joseph Wang, DSc, professor in the Aiiso Yufeng Li Family Department of Chemical and Nano Engineering at the UC San Diego Jacobs School of Engineering. Saha is co-first author of the team’s published paper in PNAS titled “A wearable patch for continuous levodopa monitoring in sweat: Towards exertion and power-free pharmacodynamic assessment in Parkinson’s disease.” In their paper the authors wrote in summary, “Overall, our easy-to-use, energy-efficient wearable supports real-time, stimulation-free monitoring, potentially enabling at-home dosage adjustments and paving the way for future autonomous closed-loop L-dopa therapeutic system development.”

Parkinson’s disease is the second most common and fastest-growing neurodegener­ative disorder worldwide, the author wrote. “While no cure for PD exists, levodopa (L-dopa) is the most effective symptomatic treatment, which is typically administered via oral tablets or capsules, and in advanced cases, through inhaled powder or continuous intrajejunal or subcutaneous infusions.” Prescribing the right dose is challenging: reducing levodopa leaves patients unable to move, while too much triggers severe, uncontrollable jerking movements. Initially, the drug’s effects can last several hours.

But as the disease progresses, the therapeutic window narrows down to two hours. Currently, clinicians must rely on subjective patient diaries to adjust treatment. Unfortunately, these methods fail to catch dangerous dosing gaps. “Precision management of Parkinson’s disease (PD) requires frequent levodopa (L-dopa) dose adjustments, yet current monitoring relies on subjective symptom reporting and infrequent blood testing,” the team continued.

Levodopa monitoring patch showing the assembly of the hydrogel and levodopa sensor with the paper fluidic channel on the fingertip. [Tamoghna Saha.]
Levodopa monitoring patch showing the assembly of the hydrogel and levodopa sensor with the paper fluidic channel on the fingertip. [Tamoghna Saha.]

Saha and the engineering team developed the new finger patch technology in joint collaboration with the lab of Irene Litvan, MD, MPhil, professor in the department of neurosciences at UC San Diego School of Medicine. The project is part of a longstanding collaboration between the Wang and Litvan teams to develop wearable levodopa monitors that can improve personalized care for people living with PD.

 

Worn on the fingertip, which is packed with a high density of sweat glands, the patch is equipped with a specially engineered absorbent gel that acts like a sweat sponge. The gel contains a highly-concentrated mixture of salts and benign solvents—and that draws sweat out of the pores, since water naturally flows toward areas with higher salt concentrations. Collected sweat is drawn into a serpentine fluidic channel with a self-powered levodopa biosensor connected to a wireless transmitter.

When levodopa in the patient’s sweat comes into contact with enzymes embedded in the patch it triggers a chemical reaction, which in turn generates a small, measurable voltage. This chemical reaction is what powers the patch. The amount of voltage generated also serves as an indicator of the patient’s levodopa level, such that lower voltage signals low levels, while higher voltage signals high levels.

Unassembled integrated levodopa monitoring patch. [David Baillot (University of California, San Diego, San Diego, CA).]
Unassembled integrated levodopa monitoring patch. [David Baillot (University of California, San Diego, San Diego, CA).]

Experimental results from three to five healthy participants and four individuals with PD indicated that levodopa concentrations in sweat measured by the patch are strongly correlated with blood concentrations measured by high-performance liquid chromatography. The patches captured pharmacodynamic responses and patient-specific levodopa clearance trends that could be used to calibrate dosage estimates for individuals.

The data revealed that individuals with Parkinson’s clear levodopa from their systems significantly faster than healthy individuals. This result explains why a patient’s Parkinson’s symptoms can deteriorate so suddenly, the researchers noted.

This technology could lay the groundwork for a closed-loop system, where a levodopa monitoring patch could communicate with a pump to automatically deliver the precise doses of the drug right when the body needs it, the authors suggested. “This approach establishes a foundation for real-time, at-home therapeutic optimization and advances the development of future closed-loop treatment systems for PD.”

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Research progress on the α-synuclein-lysosome axis in Parkinson’s disease: molecular mechanisms of protein aggregation, autophagy dysfunction, and therapeutic targeting

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder worldwide, characterized pathologically by the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies, which predominantly consist of misfolded α-synuclein (α-Syn) aggregates. Recent advances have highlighted the critical role of the interplay between α-Syn and lysosomal function, termed the α-Syn-lysosome axis, as a central mechanism underlying PD pathogenesis. This review systematically summarizes the molecular mechanisms driving α-Syn aggregation and the lysosomal dysfunction contributing to impaired autophagy-lysosome pathway (ALP) activity. We further discuss emerging therapeutic strategies targeting this axis to restore lysosomal function and mitigate α-Syn toxicity. By integrating the latest findings from molecular biology, cell biology, and preclinical studies, this article aims to elucidate the complex regulatory network of the α-Syn-lysosome axis and provide a theoretical foundation for the development of novel therapeutic interventions for PD.

From clinical phenotypes to molecular precision: multimodal biomarkers for progressive supranuclear palsy

Progressive Supranuclear Palsy (PSP) is the most prevalent primary 4R-tauopathy, characterized by the pathogenic accumulation of misfolded tau protein within neurons and glial cells. Historically, clinical diagnosis relied upon the identification of Richardson’s Syndrome, however, the recognition of diverse clinical phenotypes that overlap with Parkinson’s disease, corticobasal syndrome, and frontotemporal dementia has complicated the diagnostic landscape and hindered the success of developing therapeutic interventions. As the field transitions toward a precision medicine paradigm, there is a growing need for validated biomarkers that can provide molecular specificity, facilitate early diagnosis, and accurately track disease progression. This paper reviews the recent advancements in neuroimaging and fluid-based biomarkers, assessing their potential to delineate PSP from similar neurodegenerative conditions and unlock the 4R-tau therapeutic pipeline. In the domain of neuroimaging, while structural magnetic resonance imaging (MRI) and the Magnetic Resonance Parkinsonism Index (MRPI) continue to provide measures of subcortical atrophy, the emergence of second-generation tau-selective positron emission tomography (PET) radioligands represents a transformative shift. New tau PET tracers offer the ability to visualize tau pathology in vivo, providing a more direct assessment of the underlying proteinopathy than traditional volumetric measures. These advancements are complemented by significant progress in fluid biomarkers. Plasma phosphorylated tau at residue 217 (p-tau217) has gained prominence as a robust marker for Alzheimer’s disease, and its primary utility in PSP research currently serves as a critical negative signature to exclude amyloid-associated co-pathology. In contrast, novel assays targeting microtubule-binding region tau fragments show burgeoning potential for the specific identification of 4R-tau isoforms. Furthermore, neurofilament light chain (NfL) has been firmly established as a sensitive, albeit non-specific, indicator of neuroaxonal injury and clinical severity. Additional advancements with digital health approaches and electrophysiological assessments add to the opportunities for improved objective measures. This review concludes that the shift from clinical-only diagnostic criteria to a biomarker-enabled molecular framework is the necessary catalyst for developing effective disease-modifying therapies for PSP and related 4R-tauopathies. The synthesis of these multimodal biomarkers into a unified framework will be essential to improve participant stratification, enable the use of adaptive trial models, and provide supportive evidence of target engagement for future clinical trials.

Opinion: Pete Hegseth, ‘The Odyssey,’ and the testosterone myth

The past week has brought us two similar ideas of masculinity, separated by 4,000 years. When Defense Secretary Pete Hegseth announced the initiation of testosterone screening in all U.S. servicemembers 30 and older under the title “The High T Department of War,” his vision was as clear as an IMAX projection of Odysseus: a warrior in his physical prime, lethal in battle, unquestionably ascendant in the home, anointed by god.

Both of these men, the classical hero and the optimized modern soldier, are fantasies. But I’m worried Hegseth’s vision is a tragedy in the making

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Curcumin attenuates α-synuclein pathology in Parkinson’s disease model mice through modulation of UBC9-associated SUMOylation signaling

BackgroundPost-translational modifications, particularly SUMOylation, plays a crucial role in α-synuclein (α-syn) aggregation, a key pathological feature of Parkinson’s disease (PD). Curcumin, a natural polyphenol, has shown neuroprotective potential, but its effects on SUMOylation-related signaling in PD remain unclear.ObjectiveThis study aimed to investigate whether curcumin modulates α-syn SUMOylation and to elucidate the underlying molecular mechanisms in PD model mice.MethodsA PD model was established in male C57BL/6 mice via unilateral intrastriatal injection of α-syn preformed fibrils (PFFs). Six months after α-syn PFFs injection, mice were treated intravenously with curcumin (25 mg/kg/day) or vehicle for 1 month. Behavioral tests (open field, rotarod) assessed motor function. Neuropathology was evaluated by immunohistochemistry and western blotting for tyrosine hydroxylase (TH), phosphorylated α-syn (p-syn), SUMOylation pathway components (SUMO1, SAE2, UBC9, PIAS1/2), and ubiquitin. Striatal dopamine levels were measured by HPLC.ResultsCurcumin treatment ameliorated motor deficits and anxiety-like behaviors in PD mice. It partially preserved dopaminergic neurons and reduced p-syn aggregation in the substantia nigra, accompanied by increased striatal dopamine levels. Mechanistically, curcumin was associated with reduced SUMO1 and increased ubiquitin levels, suggesting modulation of SUMOylation-related signaling. Among SUMOylation enzymes, UBC9 expression was decreased, whereas E1 (SAE2) and E3 (PIAS1/2) components were not substantially affected.ConclusionOur findings demonstrated that curcumin exerted neuroprotective effects in a PD model by attenuating α-syn pathology. The protective mechanism involves the inhibition of α-syn SUMOylation, primarily through the downregulation of the UBC9 enzyme. This study identifies UBC9-mediated SUMOylation as a potential target for curcumin and highlight a promising strategy for modifying α-syn-associated pathology in PD.

Targeting mitochondria for the treatment of neurodegenerative diseases

Mitochondria are central regulators of cellular metabolism, redox balance, calcium signaling, and cell survival, making them essential for neuronal function. Because neurons rely heavily on mitochondrial oxidative phosphorylation to meet their high energetic demands, mitochondrial dysfunction has emerged as a key pathogenic driver in major neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Defects in mitochondrial bioenergetics, excessive reactive oxygen species production, impaired mitochondrial dynamics, disrupted mitophagy, and dysregulated calcium handling collectively contribute to neuronal damage, synaptic dysfunction, and neuroinflammation. These insights have prompted growing interest in therapeutic strategies that directly target mitochondria to restore organelle homeostasis. Recent advances in chemical biology and nanomedicine have enabled the development of mitochondria-targeted ligands, peptide-based targeting systems, and carrier or nanotechnology-enabled delivery platforms designed to overcome biological barriers and selectively deliver therapeutic cargos to mitochondria within the central nervous system. In this Review, we summarize mitochondrial pathological mechanisms in neurodegenerative diseases and discuss emerging mitochondria-targeted therapeutic strategies, highlighting delivery technologies, therapeutic modalities, and translational challenges. Although most strategies remain at the preclinical or proof-of-principle stage, these advances are beginning to shape a conceptual framework for precision mitochondrial medicine, with the longer-term goal of developing disease-modifying interventions for neurodegenerative disorders.

Blood Protein Panel May Help Distinguish Major Dementia Types

Diagnosing dementia is rarely straightforward, particularly early in the disease course. Alzheimer’s disease, dementia with Lewy bodies, and frontotemporal dementia can overlap clinically, while mixed pathology is common in older patients. This creates a major barrier for precision medicine: treatment selection, trial enrolment, prognosis, and patient counselling increasingly require a more biologically grounded diagnosis.

Blood biomarkers have already begun to change Alzheimer’s disease diagnostics, especially for detecting amyloid and tau pathology. But the field still lacks robust plasma tools for distinguishing Alzheimer’s disease from dementia with Lewy bodies (DLB) or frontotemporal dementia (FTD).

Proteomics across dementia cohorts

A new study, published in Nature Aging, used proximity extension assay proteomics to profile plasma proteins across international dementia cohorts. In the discovery phase, researchers analyzed more than 1,300 plasma samples, including controls and individuals across preclinical, mild cognitive impairment, and dementia stages of Alzheimer’s disease, dementia with Lewy bodies, and frontotemporal dementia.

The analysis identified more than 200 dysregulated proteins across disease groups. For Alzheimer’s disease, glial fibrillary acidic protein, or GFAP, showed the strongest increase across the disease continuum. Neurofilament light chain also rose with clinical stage, while several other proteins declined as Alzheimer’s disease progressed. However, the authors emphasize that these proteomic markers did not outperform established plasma markers of amyloid and tau pathology for detecting Alzheimer’s disease.

The more clinically novel findings came from the non-Alzheimer’s dementias. In dementia with Lewy bodies, integrin alpha-V and integrin alpha-M were consistently reduced, including in analyses stratified by amyloid status and in autopsy-confirmed Lewy body disease. The same integrin-related signal was also seen in Parkinson’s disease data from the PPMI cohort, supporting a broader link to Lewy body pathology.

For frontotemporal dementia, neurofilament light chain remained one of the strongest markers, consistent with its role as a general marker of neuroaxonal injury. Lower GFAP helped distinguish frontotemporal dementia from Alzheimer’s disease, while proteins such as OSM appeared more relevant in earlier frontotemporal degeneration.

A 21-protein dementia panel

The researchers then refined these signals into a custom 21-protein plasma panel and tested it in an independent multicenter cohort. The panel showed its strongest value in differential diagnosis, helping separate dementia with Lewy bodies and frontotemporal dementia from both controls and Alzheimer’s disease dementia. Its performance was moderate to good across these comparisons, suggesting that plasma proteomics may be most useful as an added layer of biological stratification when clinical symptoms overlap.

These values are not sufficient to replace specialist clinical assessment, CSF testing, imaging, or established Alzheimer’s blood biomarkers. But they suggest that plasma proteomics could provide clinically useful support where diagnostic uncertainty remains high.

Toward biomarker-based dementia stratification

The immediate relevance is not simply another biomarker list. The study addresses a practical gap in dementia medicine: identifying scalable blood-based tools that help separate biologically different diseases with overlapping symptoms. That could improve referral pathways, enrich clinical trials with the right patient populations, and support future disease-modifying therapies beyond Alzheimer’s disease.

Important limitations remain. Many DLB and FTD diagnoses were clinical rather than autopsy-confirmed, prodromal groups were relatively small, and biomarker performance may depend on assay platform and cohort calibration. Mixed pathology, especially coexisting Alzheimer’s and Lewy body disease, remains a major challenge.

Even so, the study provides a strong proof of concept. Plasma proteomics may help move dementia diagnostics from broad syndromic categories toward molecular stratification, an essential step if precision neurology is to match the progress already seen in Alzheimer’s biomarker development.

The post Blood Protein Panel May Help Distinguish Major Dementia Types appeared first on Inside Precision Medicine.

Opinion: Beware the unintended consequences of testosterone screening for military servicemembers

When I first heard the announcement on Wednesday that the Department of Defense will begin a mandatory testosterone screening program for service members, my mind naturally leapt to a series of questions derived from my career studying men’s health and population-level screening in men’s health. In particular, I fear that the widespread rollout of testosterone screening may lead to some surprising and unintended consequences that must be carefully weighed if we want to prioritize the health of U.S. servicemembers.

As a practicing urologist and health outcomes researcher, I have seen firsthand how testosterone supplementation has received growing interest in recent years. I have also studied the impacts and implementation other types of screening tests, including among military servicemembers.  As with any type of population-level medical screening, a careful examination of risks and benefits is vital.

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Circuit logic of oxytocin and vasopressin complementary actions

Oxytocin (OT) and vasopressin (VP) are evolutionarily conserved neuropeptides that regulate social behavior, emotional processing and physiological homeostasis. Although traditionally studied as individual modulators of affiliation, stress and autonomic function, emerging evidence indicates that their actions are best understood at the level of neural circuits. Advances in optogenetics, cell-type-specific electrophysiology and systems neuroscience have revealed that OT and VP act within distributed networks through receptor-defined microcircuits composed of excitatory and inhibitory neuronal populations, astrocytes and long-range projections. Within these circuits, OT and VP can exert complementary, synergistic or opposing effects depending on receptor localization, cellular identity and network state. Here, we synthesize recent circuit-level and electrophysiological evidence to propose a framework in which OT and VP operate as a coordinated neuromodulatory axis. We argue that the functional consequences of OT/VP signaling emerge not from peptide identity alone, but from their engagement of recurrent circuit motifs that redistribute excitation and inhibition across neural networks. These motifs provide a mechanistic substrate for regulating transitions between competing behavioral and physiological states, including social safety vs. threat, affiliation vs. avoidance, and parasympathetic vs. sympathetic dominance. We further discuss how disruption of receptor topology, synaptic integration and circuit architecture may contribute to neurodevelopmental, psychiatric and stress-related disorders. By shifting the focus from peptide-centric models to circuit-level mechanisms, this framework reconciles seemingly contradictory findings across brain regions and behavioral paradigms, and provides a foundation for the development of next-generation circuit-based therapeutic strategies targeting the oxytocin-vasopressin axis.

Parkinson’s in the Clinic, Insilico enters Phase III, Vertex Acquires Crinetics

Promise hits Parkinson’s disease therapy, as a Phase I/II clinical study has demonstrated the feasibility of transplanting stem-cell-derived dopamine progenitor cells into the brain. In preclinical research, a new platform uses the brain’s fluid transport pathways to effectively deliver AAVs to therapeutic targets in mice. We’ll also cover the accelerating infrastructure moment for AI-driven drug discovery, with billion-dollar investments flowing into end-to-end platforms driven by models and compute, rather than single drug assets. In business, Insilico’s revenue leaps as the company’s AI-developed lead candidate moves to Phase III, while Vertex acquires Crinetics for $10 billion.

 

Listed below are links to the GEN stories referenced in this episode of Touching Base:

Engineered AAVs Harness Glymphatic System to Reach Brain Targets in Mice
GEN, July 9, 2026

Stem Cell Therapy Shows Promise in First Human Parkinson’s Disease Trial
GEN, July 9, 2026

Pharma Races to Scale AI as Billions Flow into Drug Discovery
By Fay Lin, PhD, GEN Edge, July 6, 2026

StockWatch: Insilico Projects Profit, Revenue Leaps as AI-Developed Lead Candidate Moves to Phase III
By Alex Philippidis, GEN Edge, July 12, 2026

Vertex Eyes Expansion Beyond Cystic Fibrosis with Planned $10B Crinetics Buyout
By Alex Philippidis, GEN Edge, July 7, 2026

Top 20 Drugs Heading for the Patent Cliff, 2026-2029
By Alex Philippidis, GEN Magazine, Nov 1, 2025

Touching Base Podcast
Hosted by Corinna Singleman, PhD

Behind the Breakthroughs
Hosted by Jonathan D. Grinstein, PhD

The State of Biologics Testing 2026
Charles River Laboratories and GEN, June 10, 2026  

 


 

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