Parkinson's Disease: Difference between revisions

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== General information ==
== General information ==


The theme of 2025/26 is Parkinson's disease and levodopa monitoring. Parkinson's disease is a progressive neurodegenerative disorder caused by the loss of dopamine-producing neurons in the substantia nigra region of the brain. This results in a severe dopamine deficiency in the basal ganglia, which are critical for initiating and smoothing movement. The primary motor symptoms advancing from this deficit include tremor, muscle rigidity, slowness of movement, and postural instability.<ref>AANS. (2024, April 30). ''Parkinson’s Disease''. American Association of Neurological Surgeons. <nowiki>https://www.aans.org/patients/conditions-treatments/parkinsons-disease</nowiki></ref> Generally, the management of motor symptoms relies on the administration of levodopa (L-Dopa), a dopamine precursor that can cross the blood-brain barrier, unlike dopamine itself.<ref>StatPearls. (n.d.). ''Levodopa''. In NCBI Bookshelf. <nowiki>https://www.ncbi.nlm.nih.gov/books/NBK482140/</nowiki> — “Unlike dopamine, levodopa can cross the blood-brain barrier (BBB).”</ref> <ref>Chen, Y., et al. (2025). ''Translation-Neurodegeneration'', 14:10. “Unlike dopamine, levodopa crosses the blood–brain barrier …” <nowiki>https://doi.org/10.1186/s40035-025-00467-8</nowiki></ref>Levodopa is absorbed from the gastrointestinal tract and transported via the bloodstream to the brain, where it is decarboxylated into dopamine to restore motor function. Consequently, the concentration of levodopa in the blood serum directly influences the therapeutic effect and the onset of motor complications. A standard therapeutic range for plasma levodopa is typically considered to be between 2 - 7.6 µM following a dose.<ref name=":0">Probst, D.; Batchu, K.; Younce, J. R.; Sode, K. Levodopa: From Biological Significance to Continuous Monitoring. ACS Sensors 2024, 9 (8), 3828–3839.\href{<nowiki>https://doi.org/10.1021/acssensors.4c00602}{https://doi.org/10.1021/acssensors.4c00602}</nowiki> </ref> As the disease progresses, the relationship between dose and clinical response becomes unpredictable, leading to motor fluctuations and dyskinesias. Therefore, monitoring levodopa levels serves as a crucial tool for optimizing dosing regimens. There is no cure for Parkinson's disease, although medications and therapies can manage the symptoms. In advanced cases, patients may undergo surgical treatments like deep brain stimulation to help control motor symptoms.<ref>Perestelo-Pérez, L., et al. (2019). ''Efficacy and Safety of Deep Brain Stimulation in the Treatment of Parkinson’s Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials.'' ''Frontiers in Neurology'', 10, 857. <nowiki>https://doi.org/10.3389/fneur.2019.00857</nowiki></ref><ref>Odekerken, V. J. J., et al. (2015). ''Deep brain stimulation in Parkinson's disease: meta-analysis of randomized controlled trials.'' ''Movement Disorders'', 30(10), 1501–1510. <nowiki>https://doi.org/10.1002/mds.26237</nowiki></ref>
The theme of 2026 is Parkinson's disease and levodopa monitoring. Parkinson's disease is a progressive neurodegenerative disorder caused by the loss of dopamine-producing neurons in the substantia nigra region of the brain. This results in a severe dopamine deficiency in the basal ganglia, which are critical for initiating and smoothing movement. The primary motor symptoms advancing from this deficit include tremor, muscle rigidity, slowness of movement, and postural instability.<ref>AANS. (2024, April 30). ''Parkinson’s Disease''. American Association of Neurological Surgeons. <nowiki>https://www.aans.org/patients/conditions-treatments/parkinsons-disease</nowiki></ref> Generally, the management of motor symptoms relies on the administration of levodopa (L-Dopa), a dopamine precursor that can cross the blood-brain barrier, unlike dopamine itself.<ref>StatPearls. (n.d.). ''Levodopa''. In NCBI Bookshelf. <nowiki>https://www.ncbi.nlm.nih.gov/books/NBK482140/</nowiki> — “Unlike dopamine, levodopa can cross the blood-brain barrier (BBB).”</ref> <ref>Chen, Y., et al. (2025). ''Translation-Neurodegeneration'', 14:10. “Unlike dopamine, levodopa crosses the blood–brain barrier …” <nowiki>https://doi.org/10.1186/s40035-025-00467-8</nowiki></ref>Levodopa is absorbed from the gastrointestinal tract and transported via the bloodstream to the brain, where it is decarboxylated into dopamine to restore motor function. Consequently, the concentration of levodopa in the blood serum directly influences the therapeutic effect and the onset of motor complications. A standard therapeutic range for plasma levodopa is typically considered to be between 2 - 7.6 µM following a dose.<ref name=":0">Probst, D.; Batchu, K.; Younce, J. R.; Sode, K. Levodopa: From Biological Significance to Continuous Monitoring. ACS Sensors 2024, 9 (8), 3828–3839.\href{<nowiki>https://doi.org/10.1021/acssensors.4c00602}{https://doi.org/10.1021/acssensors.4c00602}</nowiki> </ref> As the disease progresses, the relationship between dose and clinical response becomes unpredictable, leading to motor fluctuations and dyskinesias. Therefore, monitoring levodopa levels serves as a crucial tool for optimizing dosing regimens. There is no cure for Parkinson's disease, although medications and therapies can manage the symptoms. In advanced cases, patients may undergo surgical treatments like deep brain stimulation to help control motor symptoms.<ref>Perestelo-Pérez, L., et al. (2019). ''Efficacy and Safety of Deep Brain Stimulation in the Treatment of Parkinson’s Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials.'' ''Frontiers in Neurology'', 10, 857. <nowiki>https://doi.org/10.3389/fneur.2019.00857</nowiki></ref><ref>Odekerken, V. J. J., et al. (2015). ''Deep brain stimulation in Parkinson's disease: meta-analysis of randomized controlled trials.'' ''Movement Disorders'', 30(10), 1501–1510. <nowiki>https://doi.org/10.1002/mds.26237</nowiki></ref>


== History and Current Situation 0f Parkinson's Disease ==
== History and Current Situation 0f Parkinson's Disease ==
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== Levodopa Biosensors ==
== Levodopa Biosensors ==
A continuous wearable L-Dopa sensor would help doctors to make informed decisions about personalized patient treatment and how to adjust medication in real-time to reduce Levodopa fluctuations. Continuous sensing would also help researchers better understand the pharmacokinetics of Levodopa across different bodily fluids, namely ISF, blood, and cerebrospinal fluid (CSF). This could improve treatment strategies for late-stage PD patients and also help make a step towards the long-term vision of closed-loop Levodopa therapy for PD wherein continual oral administration would no longer be required, improving the patients’ quality of life.<ref>Probst, D.; Kartheek Batchu; Younce, J. R.; Sode, K. Levodopa: From Biological Significance to Continuous Monitoring. ''ACS Sensors'' '''2024''', ''9'' (8), 3828–3839. <nowiki>https://doi.org/10.1021/acssensors.4c00602</nowiki></ref>
A continuous wearable L-Dopa sensor would help doctors to make informed decisions about personalized patient treatment and how to adjust medication in real-time to reduce Levodopa fluctuations. Continuous sensing would also help researchers better understand the pharmacokinetics of Levodopa across different bodily fluids, namely ISF, blood, and cerebrospinal fluid (CSF). This could improve treatment strategies for late-stage PD patients and also help make a step towards the long-term vision of closed-loop Levodopa therapy for PD wherein continual oral administration would no longer be required, improving the patients’ quality of life.<ref name=":0" />

Latest revision as of 11:06, 19 November 2025

General information

The theme of 2026 is Parkinson's disease and levodopa monitoring. Parkinson's disease is a progressive neurodegenerative disorder caused by the loss of dopamine-producing neurons in the substantia nigra region of the brain. This results in a severe dopamine deficiency in the basal ganglia, which are critical for initiating and smoothing movement. The primary motor symptoms advancing from this deficit include tremor, muscle rigidity, slowness of movement, and postural instability.[1] Generally, the management of motor symptoms relies on the administration of levodopa (L-Dopa), a dopamine precursor that can cross the blood-brain barrier, unlike dopamine itself.[2] [3]Levodopa is absorbed from the gastrointestinal tract and transported via the bloodstream to the brain, where it is decarboxylated into dopamine to restore motor function. Consequently, the concentration of levodopa in the blood serum directly influences the therapeutic effect and the onset of motor complications. A standard therapeutic range for plasma levodopa is typically considered to be between 2 - 7.6 µM following a dose.[4] As the disease progresses, the relationship between dose and clinical response becomes unpredictable, leading to motor fluctuations and dyskinesias. Therefore, monitoring levodopa levels serves as a crucial tool for optimizing dosing regimens. There is no cure for Parkinson's disease, although medications and therapies can manage the symptoms. In advanced cases, patients may undergo surgical treatments like deep brain stimulation to help control motor symptoms.[5][6]

History and Current Situation 0f Parkinson's Disease

Although tremor-like syndromes appeared in historical accounts, Parkinson’s disease was first clearly defined in 1817, when James Parkinson published An Essay on the Shaking Palsy, describing six cases with trembling at rest, slowness, and a peculiar posture. [7] In the late 19th century, Jean-Martin Charcot refined this clinical picture, distinguishing rigidity and bradykinesia, and popularized the eponym “Parkinson’s disease.” [8] Pathological and biochemical studies in the 20th century uncovered degeneration of the substantia nigra and the presence of Lewy bodies, leading to the understanding of dopamine deficiency as a core mechanism. [9] Treatment evolved from early anticholinergic drugs to the introduction of levodopa in the 1960s, and later to surgical and neuromodulation techniques such as deep brain stimulation (DBS). [9]

Parkinson’s disease (PD) is now a rapidly growing global health challenge. In 2021, about 11.77 million people worldwide were estimated to be living with PD, with age-standardized prevalence at ~ 138.6 per 100,000 and incidence at ~ 15.63 per 100,000.[10] Over the past three decades, rates of PD incidence, prevalence, and disability (DALYs) have all increased, particularly in men. [10] Projections suggest that by 2050, the number of people with PD could more than double to ~ 25.2 million, largely driven by aging populations. [11]

On a biological level, PD is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta and accumulation of α-synuclein aggregates (Lewy bodies). [9] Both genetic factors (e.g. LRRK2, GBA) and environmental exposures (e.g. pesticides) contribute to disease risk. [9] Clinically, PD manifests with motor symptoms (bradykinesia, rigidity, resting tremor, postural instability) and non-motor features (such as loss of smell, sleep disorder, autonomic problems, depression), many of which may begin years before motor onset. [9] Diagnosis is primarily clinical, based on a neurological examination and response to dopaminergic therapy; research into biomarkers and imaging (e.g. DAT scans) is ongoing but not yet standard. [9] Treatment remains symptomatic: levodopa is the cornerstone, although long-term use often leads to motor fluctuations and dyskinesias, and DBS is an option for selected patients. [9] Major challenges include disease heterogeneity, the lack of reliable biomarkers for early detection or progression, and unequal access to advanced therapies — but wearable and biosensor technologies are promising tools for monitoring and early diagnosis.

Role of Levodopa(L-Dopa) in the Treatment of Parkinson's Disease

Levodopa has remained the benchmark treatment for PD since its introduction around 1970. It has a therapeutic reference range of 0.76-1.25 μM in cerebrospinal fluid (CSF) and 2-7.6 μM in blood plasma [4]. It has a short half-life of 30-90 minutes, so it is typically administered in combination with an AAADI (aromatic L-amino acid decarboxylase inhibitor), like carbidopa (exclusively an L- isomer) or benserazide (a racemic mixture), to increase the efficacy of L-Dopa entering into the CNS (central nervous system) by minimizing the peripheral conversion of L-Dopa to dopamine [12].

Long-term usage of L-Dopa can lead to complications. Early in PD, the brain can store and regulate dopamine well, providing stable symptom relief. However, as the disease progresses to later stages, this ability of the brain weakens, resulting in greater fluctuations in L-Dopa levels [4]. This highlights the need for precise L-Dopa dosing. Figure 1 illustrates how the narrowing of the L-Dopa therapeutic window over time leads to levodopa-induced dyskinesia (LID; involuntary, uncontrolled movements) and off-time (return of PD symptoms).

State of the Art

Current Methods to Measure L-Dopa

The current gold standards to measure L-Dopa are Liquid-Chromatography-Mass Spectrometry (LC-MS) and High Performance Liquid Chromatography (HPLC). However, these methods are time-consuming, costly, and are performed in centralized laboratories, making them impractical for timely adjustment of L-Dopa does for PD patients. This causes a need for reliable, affordable, quick, and more user-friendly L-Dopa testing.[13]

Matrix

Several matrices are available in which L-Dopa can be measured by a biosensor, namely blood (plasma), sweat, or interstitial fluid (ISF). ISF has been selected as the matrix for SensUs 2026, due to the ease of accessibility compared to blood plasma and the more stable composition compared to sweat [14].

Currently, ISF is used for continuous glucose monitoring. Interstitial skin fluid (ISF) makes up 75% of extracellular fluid and 15-25% of body weight [15]. It surrounds cells and tissues, serving as an interface between blood and cells. It may be a source of biomarkers in addition to blood biomarkers, as research shows that 83% of proteins found in blood serum are also present in ISF, but 50% of proteins in ISF are not found in serum [15].

The approximate concentration range of L-Dopa in ISF is 3-50 μM. SensUs 2026 proposes to focus on the upper ranges of the concentration, in order to manage levodopa-induced dyskinesia.

Test Stability

In solution, L-Dopa is chemically unstable and naturally degrades over time due to interactions with proteins and oxidative processes, leading to its conversion to dopamine or other byproducts in the L-Dopa metabolic pathway. The degradation rate can be slowed down by [16]:

  • refrigeration or freezing: stable for approximately one week;
  • ascorbate addition: stable for approximately three days.

Levodopa Biosensors

A continuous wearable L-Dopa sensor would help doctors to make informed decisions about personalized patient treatment and how to adjust medication in real-time to reduce Levodopa fluctuations. Continuous sensing would also help researchers better understand the pharmacokinetics of Levodopa across different bodily fluids, namely ISF, blood, and cerebrospinal fluid (CSF). This could improve treatment strategies for late-stage PD patients and also help make a step towards the long-term vision of closed-loop Levodopa therapy for PD wherein continual oral administration would no longer be required, improving the patients’ quality of life.[4]

  1. ↑ AANS. (2024, April 30). Parkinson’s Disease. American Association of Neurological Surgeons. https://www.aans.org/patients/conditions-treatments/parkinsons-disease
  2. ↑ StatPearls. (n.d.). Levodopa. In NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK482140/ — “Unlike dopamine, levodopa can cross the blood-brain barrier (BBB).”
  3. ↑ Chen, Y., et al. (2025). Translation-Neurodegeneration, 14:10. “Unlike dopamine, levodopa crosses the blood–brain barrier …” https://doi.org/10.1186/s40035-025-00467-8
  4. ↑ 4.0 4.1 4.2 4.3 Probst, D.; Batchu, K.; Younce, J. R.; Sode, K. Levodopa: From Biological Significance to Continuous Monitoring. ACS Sensors 2024, 9 (8), 3828–3839.\href{https://doi.org/10.1021/acssensors.4c00602}{https://doi.org/10.1021/acssensors.4c00602}
  5. ↑ Perestelo-Pérez, L., et al. (2019). Efficacy and Safety of Deep Brain Stimulation in the Treatment of Parkinson’s Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Frontiers in Neurology, 10, 857. https://doi.org/10.3389/fneur.2019.00857
  6. ↑ Odekerken, V. J. J., et al. (2015). Deep brain stimulation in Parkinson's disease: meta-analysis of randomized controlled trials. Movement Disorders, 30(10), 1501–1510. https://doi.org/10.1002/mds.26237
  7. ↑ Parkinson, J. (1817). An Essay on the Shaking Palsy. London: Whittingham & Rowland.
  8. ↑ LaFia, D. J. (1967). The Shaking Palsy 1817–1967. JAMA.
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 Lees, A. J. (2017). The history of Parkinson’s disease: early clinical descriptions and neurological therapies. Brain, 140(3), 843–848. https://doi.org/10.1093/brain/awx035
  10. ↑ 10.0 10.1 GBD 2021 Parkinson’s Disease Collaborators. (2024). Global burden of Parkinson’s disease from 1990 to 2021: a population-based study. Lancet Neurology / GBD Data.
  11. ↑ Xie, Y., et al. (2024). Projections for prevalence of Parkinson’s disease by 2050: modeling study based on Global Burden of Disease 2021. BMJ / PubMed.
  12. ↑ Carvey, P. M. Dopa-Decarboxylase Inhibitors. Encyclopedia of Movement Disorders 2010, 313–316. https://doi.org/10.1016/b978-0-12-374105-9.00318-x
  13. ↑ Kuldeep Mahato; Moon, J.-M.; Chochanon Moonla; Longardner, K.; Ghodsi, H.; Litvan, I.; Wang, J. Biosensor Strip for Rapid On‐Site Assessment of Levodopa Pharmacokinetics along with Motor Performance in Parkinson’s Disease. Angewandte Chemie International Edition 2024. https://doi.org/10.1002/anie.202403583
  14. ↑ Peterson, K. L.; Shukla, R. P.; Daniele, M. A. Percutaneous Wearable Biosensors: A Brief History and Systems Perspective. Advanced Sensor Research 2024. https://doi.org/10.1002/adsr.202400068
  15. ↑ 15.0 15.1 Samant, P. P., Niedzwiecki, M. M., Raviele, N., Tran, V., Mena-Lapaix, J., Walker, D. I., Felner, E. I., Jones, D. P., Miller, G. W., Prausnitz, M. R. (2020). Sampling interstitial fluid from human skin using a microneedle patch. Science Translational Medicine, 12(571). https://doi.org/10.1126/scitranslmed.aaw0285
  16. ↑ Pappert, E. J.; Buhrfiend, C.; Lipton, J. W.; Carvey, P. M.; Stebbins, G. T.; Goetz, C. G. Levodopa Stability in Solution: Time Course, Environmental Effects, and Practical Recommendations for Clinical Use. Movement Disorders 1996, 11 (1), 24–26. https://doi.org/10.1002/mds.870110106
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