Review
Clinical Neurology
Valentina Leta, Lisa Klingelhoefer, Katherine Longardner, Marta Campagnolo, Hafize Cotur Levent, Federico Aureli, Vinod Metta, Roongroj Bhidayasiri, Guy Chung-Faye, Cristian Falup-Pecurariu, Fabrizio Stocchi, Peter Jenner, Tobias Warnecke, K. Ray Chaudhuri
Summary: Levodopa is the gold standard treatment for Parkinson's disease, but it often leads to motor and non-motor fluctuations. Gastrointestinal barriers, such as dysphagia, delayed gastric emptying, and gut dysbiosis, can affect levodopa absorption and response. Managing gastrointestinal dysfunction is crucial for optimizing levodopa therapy.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Chemistry, Organic
Alexander D. Huters, James Stambuli, Russell C. Klix, Mark A. Matulenko, Vincent S. Chan, Justin Simanis, David R. Hill, Rajarathnam E. Reddy, Timothy B. Towne, John R. Bellettini, Brian J. Kotecki, Benoit Cardinal-David, Jianguo Ji, Eric A. Voight, Minshan Shou, Selvakumar Balaraman, Abhishek Ashok, Soma Ghosh
Summary: This article describes the asymmetric syntheses of foslevodopa and foscarbidopa and their manufacturing process at pilot scale. The synthesis of foslevodopa involves Horner-Wadsworth-Emmons olefination reaction and enantioselective hydrogenation, while the synthesis of foscarbidopa utilizes Mizoroki-Heck reaction and enantioselective hydrazination.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Tomasz Gutowski, Ryszard Antkiewicz, Stanislaw Szlufik
Summary: This paper presents a solution for creating personalized medicine intake schedules for Parkinson's disease patients. By using machine learning models and optimization algorithms, it can reduce treatment errors and the time required to establish medication schedules, with the potential to significantly improve treatment outcomes.
Article
Clinical Neurology
Matthew Rosebraugh, Eric A. Voight, Ehab M. Moussa, Feroz Jameel, Xiaochun Lou, Geoff G. Z. Zhang, Peter T. Mayer, Deanne Stolarik, Robert A. Carr, Brian P. Enright, Wei Liu, Maurizio F. Facheris, Philip R. Kym
Summary: This study demonstrates the effectiveness of continuous subcutaneous infusion of a soluble levodopa/carbidopa phosphate prodrug combination in delivering stable levodopa exposure, potentially treating Parkinson's disease patients who are not well controlled on oral medication. The prepared drugs show high water solubility, excellent chemical stability, and good tolerability in both animals and healthy volunteers. The prepared combination supports further clinical studies as a potentially transformative option for Parkinson's disease treatment.
ANNALS OF NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ana Gabrielle Bispo, Caio S. Silva, Camille Sena-dos-Santos, Dafne Dalledone Moura, Brenda Hanae Bentes Koshimoto, Bruno Lopes Santos-Lobato, Andrea Ribeiro-dos-Santos, Giovanna C. Cavalcante
Summary: Mitophagy dysfunction caused by gene mutations is associated with the development of Parkinson's Disease (PD). However, the association between the variants of mitophagy-related genes and the treatment with levodopa (LD) in PD patients has not been well explored. This study investigated the association of 14 variants of the PRKN gene with LD treatment in PD patients. The results suggest that while age at onset of symptoms, duration of PD, and LD treatment and dosage can influence the occurrence of dyskinesia, the investigated PRKN variants did not show a significant association.
Review
Pharmacology & Pharmacy
Peter Kempster, Andrew Ma
Summary: A large proportion of drugs for neurological disorders are derived from naturally occurring compounds, especially plant alkaloids. The treatment of Parkinson's disease has strong botanical origins, with plant-derived substances playing a significant role. The interaction between plant compounds and animal dopaminergic systems has deep evolutionary roots.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Clinical Neurology
Joaquim J. Ferreira, Werner Poewe, Olivier Rascol, Fabrizio Stocchi, Angelo Antonini, Joana Moreira, Bruno Guimaraes, Jose-Francisco Rocha, Patricio Soares-da-Silva
Summary: This study evaluated the effects of opicapone on levodopa plasma pharmacokinetics and motor response. The results showed that opicapone can increase the bioavailability of levodopa, decrease off time, and increase on time.
MOVEMENT DISORDERS
(2022)
Review
Pharmacology & Pharmacy
Ritam Bandopadhyay, Nainshi Mishra, Ruhi Rana, Gagandeep Kaur, Mohammed M. Ghoneim, Sultan Alshehri, Gulam Mustafa, Javed Ahmad, Nabil. A. Alhakamy, Awanish Mishra
Summary: This study focuses on the recent updates in molecular mechanisms and therapeutic approaches for the effective management of levodopa-induced dyskinesia (LID) in Parkinson's disease patients.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Clinical Neurology
Nir Giladi, Tanya Gurevich, Ruth Djaldetti, Liat Adar, Ryan Case, Shelly Leibman-Barak, Nissim Sasson, Yoseph Caraco
Summary: ND0612, a continuous subcutaneous levodopa/carbidopa delivery system, was well-tolerated and resulted in reduced OFF time and decreased plasma levodopa fluctuations when used adjunctively in PD patients. Although most patients experienced infusion site nodules, they all resolved without sequelae.
PARKINSONISM & RELATED DISORDERS
(2021)
Article
Neurosciences
Piniel Alphayo Kambey, Wen Ya Liu, Jiao Wu, Chuanxi Tang, Wokuheleza Buberwa, Adonira Saro, Alphonce M. K. Nyalali, Dianshuai Gao
Summary: This study revealed the crucial role of Amphiregulin (Areg) gene in levodopa-induced dyskinesia in Parkinson's disease. Inhibition of Areg was found to alleviate dyskinetic movements and decrease the expression of related proteins. Therefore, Areg may serve as a potential target for therapy development.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Clinical Neurology
Eva Schaeffer, Thomas Vaterrodt, Laura Zaunbrecher, Inga Liepelt-Scarfone, Kirsten Emmert, Benjamin Roeben, Morad Elshehabi, Clint Hansen, Sara Becker, Susanne Nussbaum, Jan-Hinrich Busch, Matthis Synofzik, Daniela Berg, Walter Maetzler
Summary: Our independent analysis of three PD cohorts consisting of a total of 1124 PD patients found that patients taking Levodopa CR reported a significantly higher burden of nocturnal akinesia. Higher Levodopa intake and MDS-UPDRS part IV scores predicted worse quality of sleep and higher subjective nocturnal immobility scores, while disease duration and severity were not predictive. Levodopa intake was not associated with objectively changed mobility during sleep.
JOURNAL OF NEUROLOGY
(2021)
Review
Clinical Neurology
Yu-tong Zhao, Li Liu, Yong Zhao, Zong-yi Xie
Summary: The study found that levodopa alone therapy may be superior in motor symptom relief for early Parkinson's disease patients compared to levodopa-sparing therapy, and the motor advantage of levodopa alone may increase over time. Levodopa alone therapy may increase the risk of wearing-off and dyskinesia, but the events between the two groups may not be different in the long term.
JOURNAL OF NEUROLOGY
(2022)
Review
Nutrition & Dietetics
Jacob E. Earp, Cristina Colon-Semenza, Dara L. LoBuono
Summary: Dietary habits play a significant role in individuals with Parkinson's disease (PD), as they impact disease symptoms, progression, and overall health. Specifically, protein consumption is of great interest due to its effects on disease progression and interference with levodopa medication. Proteins consist of 20 distinct amino acids (AAs), each with varying effects on health, disease progression, and medication interference. Therefore, considering the potential benefits and risks of each AA when supplementing PD patients is crucial. Additionally, the development of a precision nutritional supplement that targets the specific AAs needed for PD patients is discussed.
Article
Medicine, General & Internal
Valeria Conti, Viviana Izzo, Maria Claudia Russillo, Marina Picillo, Marianna Amboni, Cesa L. M. Scaglione, Alessandra Nicoletti, Ilaria Cani, Calogero E. Cicero, Emanuela De Bellis, Bruno Charlier, Valentina Giudice, Gerardina Somma, Graziamaria Corbi, Paolo Barone, Amelia Filippelli, Maria Teresa Pellecchia
Summary: This study revealed gender differences in LD pharmacokinetics in PD patients at their first-ever intake of LD. Women had significantly higher AUC and Cmax than men. Gender and BMI were significant predictors of AUC, while only gender predicted Cmax, and only BMI predicted t(1/2), especially in women.
FRONTIERS IN MEDICINE
(2022)
Review
Health Care Sciences & Services
Daniel van Poppelen, Annelie N. M. Tromp, Rob M. A. de Bie, Joke M. Dijk
Summary: Based on a retrospective case series and literature review, it was found that patients with Parkinson's disease who have persisting medication related motor response fluctuations despite DBS or CLI treatment may benefit from an additional or alternative treatment with either CLI or DBS.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Clinical Neurology
Valter Niemela, Anne-Marie Landtblom, Dag Nyholm, Maria Kneider, Radu Constantinescu, Martin Paucar, Per Svenningsson, Sandy Abujrais, Joachim Burman, Ganna Shevchenko, Jonas Bergquist, Jimmy Sundblom
Summary: Identifying molecular changes in Huntington's disease is crucial for therapy development. Mass-spectrometry analysis revealed differences in protein expression between HD patients and controls, with PENK levels potentially serving as a marker for the state of medium spiny neurons in HD.
MOVEMENT DISORDERS
(2021)
Review
Neurosciences
Dag Nyholm, Per M. Hellstrom
Summary: Certain studies have shown a 1.6-fold higher prevalence of Helicobacter pylori in Parkinson's disease patients compared to control populations. The eradication of Helicobacter pylori can lead to an improved response to levodopa therapy in Parkinson's disease, likely due to increased bioavailability of the drug. Patients with both Helicobacter pylori infection and Parkinson's disease on levodopa therapy tend to have worse motor control than those without the infection.
JOURNAL OF PARKINSONS DISEASE
(2021)
Article
Behavioral Sciences
Monica Scharfenort, Jonathan Timpka, Thomas Sahlstrom, Tove Henriksen, Dag Nyholm, Per Odin
Summary: This study investigated the development of close relationships between PD patients and their partners following the initiation of DAT. Results showed that partners are more likely to report changes in relationship satisfaction, with partners having higher avoidance scores and patients having higher anxiety scores.
BRAIN AND BEHAVIOR
(2021)
Article
Health Care Sciences & Services
Mezin Othman, Erik Widman, Ingela Nygren, Dag Nyholm
Summary: Patients in fluctuating stages of Parkinson's disease benefit from device-aided treatments such as continuous infusion of levodopa-carbidopa intestinal gel (LCIG). This study reports the first clinical experience of levodopa-entacapone-carbidopa intestinal gel (LECIG) therapy, showing potential for use in PD patients. Despite overall satisfaction with the size and usability of the pump, some patients experienced side effects and improvements in software technology are needed.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Clinical Neurology
Johan Virhammar, Harald Blohme, Dag Nyholm, Charalampos Georgiopoulos, David Fallmar
Summary: The study found that measuring sagittal midbrain area is more accurate and reliable than visual assessment in distinguishing between PSP patients, iNPH patients, and healthy controls. However, the presence of the hummingbird sign alone cannot fully differentiate between these two diseases, and other symptoms need to be considered in combination.
JOURNAL OF NEUROIMAGING
(2022)
Article
Neurosciences
Madelene Braun, Caroline Bjurnemark, Woosung Seo, Eva Freyhult, Dag Nyholm, Valter Niemela, Kaj Blennow, Henrik Zetterberg, David Fallmar, Kim Kultima, Johan Virhammar
Summary: Higher levels of NfL and T-tau were associated with less improvement after shunt surgery, but these CSF biomarker levels may also be elevated in patients who respond to surgery, therefore not suitable for excluding surgical candidates.
FLUIDS AND BARRIERS OF THE CNS
(2022)
Editorial Material
Health Care Sciences & Services
Dag Nyholm, Filip Bergquist
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Joao M. Sousa, Lieuwe Appel, Mathias Engstro, Stergios Papadimitriou, Dag Nyholm, Hakan Ahlstro, Mark Lubberink
Summary: In this study, a new PET/MR imaging attenuation correction (CTR-AC) method based on a composite database of Ge-68 transmission maps and T1w MR image pairs was evaluated. The results showed that CTR-AC had high accuracy and comparable performance with the best MRAC methods published so far.
PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS
(2022)
Article
Clinical Neurology
Filip Bergquist, Mats Ehrnebo, Dag Nyholm, Anders Johansson, Fredrik Lundin, Per Odin, Per Svenningsson, Fredrik Hansson, Leif Bring, Elias Eriksson, Nil Dizdar
Summary: This study compared the plasma concentrations of levodopa/carbidopa gel infusion given through subcutaneous or intravenous infusion to oral treatment in patients with advanced Parkinson disease. Results showed that subcutaneous administration achieved therapeutic levodopa concentrations quickly and stably, with good safety and tolerability outcomes.
Article
Ethics
Jennifer Drevin, Dag Nyholm, Hakan Widner, Trinette Van Vliet, Jennifer Viberg Johansson, Elena Jiltsova, Mats Hansson
Summary: This study investigated the perspectives and concerns of Parkinson's disease patients regarding the use of human embryonic stem cells (hESC) for treatment. The results showed that patients were generally positive towards the use of hESC for Parkinson's disease treatment, but also expressed concerns about transparency and prioritizing profit over patient interests.
BMC MEDICAL ETHICS
(2022)
Article
Ethics
Asa Grauman, Mats Hansson, Dag Nyholm, Elena Jiltsova, Hakan Widner, Trinette van Vliet, Jennifer Drevin
Summary: The Swedish public has a positive attitude towards using ES cells for the treatment of Parkinson's disease and other diseases. The attitude towards using ES cells for treatment of Parkinson's disease is more positive among those for whom religion is of little importance. The need to address diseases without effective treatments is considered the most important factor to consider when using ES cells for drug development.
BMC MEDICAL ETHICS
(2022)
Article
Clinical Neurology
Gustav Cedergren Weber, Jonathan Timpka, Filip Bergquist, David Backstrom, Nil Dizdar, Karin Gunnarsson, Dag Nyholm, Per Svenningsson, Per Odin
Summary: This study explored the impact of COVID-19 on motor, nonmotor, and general health aspects of Parkinson's disease and investigated the perception of symptom changes in PD patients after contracting COVID-19. The results showed that although SARS-CoV-2 infection does not seem to have a major impact on PD symptoms, COVID-19 patients reported slightly improved subjective experiences in pain, quality of life, and general motor function, sleep quality, and mood compared to the control group.
ACTA NEUROLOGICA SCANDINAVICA
(2023)
Article
Health Care Sciences & Services
Liran Karni, Ilir Jusufi, Dag Nyholm, Gunnar Oskar Klein, Mevludin Memedi
Summary: This article introduces a home monitoring system called EMPARK, aimed at improving patient empowerment and clinical care for Parkinson's Disease (PD) patients. Through design science research and user-centered design, patient and clinician interfaces were developed and evaluated. The evaluation results showed high utility and user acceptance for both the patient and clinician interfaces. The EMPARK system has the potential to empower PD patients and be used in daily care and research.
JMIR FORMATIVE RESEARCH
(2022)
Meeting Abstract
Clinical Neurology
T. Birnberg, L. Adar, W. Poewe, D. Nyholm, M. Bjornsson, M. Karlsson
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Review
Clinical Neurology
Dag Nyholm, Wolfgang H. Jost
Summary: As Parkinson's disease progresses, treatment needs to be adjusted to maintain symptom control. Device-aided therapy, such as levodopa-entacapone-carbidopa intestinal gel (LECIG) infusion, can provide continuous dopaminergic stimulation for patients with advanced PD. LECIG infusion has been shown to be clinically effective, with similar motor function improvement as standard levodopa-carbidopa intestinal gel (LCIG) infusion, but at lower overall levodopa doses. Real-world data will continue to be collected to establish the long-term efficacy and safety of LECIG infusion.
THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS
(2022)
