Browsing by Author "Naito, Anna"
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Item Finding useful biomarkers for Parkinson's disease(American Association for the Advancement of Science, 2018-08-15) Chen-Plotkin, Alice S.; Albin, Roger; Alcalay, Roy; Babcock, Debra; Bajaj, Vikram; Bowman, Dubois; Buko, Alex; Cedarbaum, Jesse; Chelsky, Daniel; Cookson, Mark; Dawson, Ted; Dewey, Richard; Foroud, Tatiana; Frasier, Mark; German, Dwight; Gwinn, Katrina; Huang, Xuemei; Kopil, Catherine; Kremer, Thomas; Lasch, Shirley; Marek, Ken; Marto, Jarrod; Merchant, Kalpana; Mollenhauer, Brit; Naito, Anna; Potashkin, Judith; Reimer, Alyssa; Rosenthal, Liana; Saunders-Pullman, Rachel; Scherzer, Clemens R.; Sherer, Todd; Singleton, Andrew; Sutherland, Margaret; Thiele, Ines; van der Brug, Marcel; Van Keuren-Jensen, Kendall; Vaillancourt, David; Walt, David; West, Andrew; Zhang, Jing; Medical and Molecular Genetics, School of MedicineParkinson’s Disease affects more than 4 million people worldwide, and biomarkers to bolster the therapeutic development pipeline are urgently needed. The recent advent of an “ecosystem” of shared biosample biorepositories and data enables us to consider how to focus PD biomarker activity to best translate efforts into real-world impact.Item Genetic Testing for Parkinson Disease: Are We Ready?(American Academy of Neurology, 2021-02) Cook, Lola; Schulze, Jeanine; Kopil, Catherine; Hastings, Tara; Naito, Anna; Wojcieszek, Joanne; Payne, Katelyn; Alcalay, Roy N.; Klein, Christine; Saunders-Pullman, Rachel; Simuni, Tatyana; Foroud, Tatiana; Medical and Molecular Genetics, School of MedicinePurpose of review: With the advent of precision medicine and demand for genomic testing information, we may question whether it is time to offer genetic testing to our patients with Parkinson disease (PD). This review updates the current genetic landscape of PD, describes what genetic testing may offer, provides strategies for evaluating whom to test, and provides resources for the busy clinician. Recent findings: Patients with PD and their relatives, in various settings, have expressed an interest in learning their PD genetic status; however, physicians may be hesitant to widely offer testing due to the perceived low clinical utility of PD genetic test results. The rise of clinical trials available for patients with gene-specific PD and emerging information on genotype-phenotype correlations are starting to shift this discussion about testing. Summary: By learning more about the various genetic testing options for PD and utility of results for patients and their care, clinicians may become more comfortable with widespread PD genetic testing in the research and clinical setting.Item Parkinson's disease variant detection and disclosure: PD GENEration, a North American study(Oxford University Press, 2024) Cook, Lola; Verbrugge, Jennifer; Schwantes-An, Tae-Hwi; Schulze, Jeanine; Foroud, Tatiana; Hall, Anne; Marder, Karen S.; Mata, Ignacio F.; Mencacci, Niccolò E.; Nance, Martha A.; Schwarzschild, Michael A.; Simuni, Tanya; Bressman, Susan; Wills, Anne-Marie; Fernandez, Hubert H.; Litvan, Irene; Lyons, Kelly E.; Shill, Holly A.; Singer, Carlos; Tropea, Thomas F.; Vanegas Arroyave, Nora; Carbonell, Janfreisy; Cruz Vicioso, Rossy; Katus, Linn; Quinn, Joseph F.; Hodges, Priscila D.; Meng, Yan; Strom, Samuel P.; Blauwendraat, Cornelis; Lohmann, Katja; Casaceli, Cynthia; Rao, Shilpa C.; Ghosh Galvelis, Kamalini; Naito, Anna; Beck, James C.; Alcalay, Roy N.; Medical and Molecular Genetics, School of MedicineVariants in seven genes (LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7 and VPS35) have been formally adjudicated as causal contributors to Parkinson's disease; however, individuals with Parkinson's disease are often unaware of their genetic status since clinical testing is infrequently offered. As a result, genetic information is not incorporated into clinical care, and variant-targeted precision medicine trials struggle to enrol people with Parkinson's disease. Understanding the yield of genetic testing using an established gene panel in a large, geographically diverse North American population would help patients, clinicians, clinical researchers, laboratories and insurers better understand the importance of genetics in approaching Parkinson's disease. PD GENEration is an ongoing multi-centre, observational study (NCT04057794, NCT04994015) offering genetic testing with results disclosure and genetic counselling to those in the US (including Puerto Rico), Canada and the Dominican Republic, through local clinical sites or remotely through self-enrolment. DNA samples are analysed by next-generation sequencing including deletion/duplication analysis (Fulgent Genetics) with targeted testing of seven major Parkinson's disease-related genes. Variants classified as pathogenic/likely pathogenic/risk variants are disclosed to all tested participants by either neurologists or genetic counsellors. Demographic and clinical features are collected at baseline visits. Between September 2019 and June 2023, the study enrolled 10 510 participants across >85 centres, with 8301 having received results. Participants were: 59% male; 86% White, 2% Asian, 4% Black/African American, 9% Hispanic/Latino; mean age 67.4 ± 10.8 years. Reportable genetic variants were observed in 13% of all participants, including 18% of participants with one or more 'high risk factors' for a genetic aetiology: early onset (<50 years), high-risk ancestry (Ashkenazi Jewish/Basque/North African Berber), an affected first-degree relative; and, importantly, in 9.1% of people with none of these risk factors. Reportable variants in GBA1 were identified in 7.7% of all participants; 2.4% in LRRK2; 2.1% in PRKN; 0.1% in SNCA; and 0.2% in PINK1, PARK7 or VPS35 combined. Variants in more than one of the seven genes were identified in 0.4% of participants. Approximately 13% of study participants had a reportable genetic variant, with a 9% yield in people with no high-risk factors. This supports the promotion of universal access to genetic testing for Parkinson's disease, as well as therapeutic trials for GBA1 and LRRK2-related Parkinson's disease.Item Participant-reported personal utility of genetic testing for Parkinson's disease and interest in clinical trial participation(Springer Nature, 2024-10-25) Oas, Hannah; Cook, Lola; Schwantes-An, Tae-Hwi; Walsh, Laurence E.; Wills, Anne-Marie; Mata, Ignacio F.; Nance, Martha A.; Beck, James C.; Naito, Anna; Marder, Karen; Alcalay, Roy N.; Verbrugge, Jennifer; Medical and Molecular Genetics, School of MedicineGenetic testing for Parkinson's disease (PD) is infrequently performed due to perceptions of low utility. We investigated the personal utility in PD GENEration and how results lead to enrollment in additional research studies. Participants (n = 972) underwent genetic testing, results disclosure, genetic counseling, and completed a survey examining the perceived personal utility of their results and interest in participating in additional studies. Most participants found their genetic test results useful, including satisfying curiosity (81%), feeling good about helping the medical community (80%), and having information to share with family (77%). There were no significant differences in responses based on result type. Forty-five percent of participants expressed interest in participating in research studies; whereas 16% of participants confirmed enrollment. Our results suggest that participants find personal utility in genetic testing regardless of results. Although participants may be interested in enrolling in additional research, they may need support and resources.Item Study in Parkinson's disease of exercise phase 3 (SPARX3): study protocol for a randomized controlled trial(BMC, 2022-10-06) Patterson, Charity G.; Joslin, Elizabeth; Gil, Alexandra B.; Spigle, Wendy; Nemet, Todd; Chahine, Lana; Christiansen, Cory L.; Melanson, Ed; Kohrt, Wendy M.; Mancini, Martina; Josbeno, Deborah; Balfany, Katherine; Griffith, Garett; Dunlap, Mac Kenzie; Lamotte, Guillaume; Suttman, Erin; Larson, Danielle; Branson, Chantale; McKee, Kathleen E.; Goelz, Li; Poon, Cynthia; Tilley, Barbara; Kang, Un Jung; Tansey, Malú Gámez; Luthra, Nijee; Tanner, Caroline M.; Haus, Jacob M.; Fantuzzi, Giamila; McFarland, Nikolaus R.; Gonzalez-Latapi, Paulina; Foroud, Tatiana; Motl, Robert; Schwarzschild, Michael A.; Simuni, Tanya; Marek, Kenneth; Naito, Anna; Lungu, Codrin; Corcos, Daniel M.; SPARX3-PSG Investigators; Medical and Molecular Genetics, School of MedicineBackground: To date, no medication has slowed the progression of Parkinson's disease (PD). Preclinical, epidemiological, and experimental data on humans all support many benefits of endurance exercise among persons with PD. The key question is whether there is a definitive additional benefit of exercising at high intensity, in terms of slowing disease progression, beyond the well-documented benefit of endurance training on a treadmill for fitness, gait, and functional mobility. This study will determine the efficacy of high-intensity endurance exercise as first-line therapy for persons diagnosed with PD within 3 years, and untreated with symptomatic therapy at baseline. Methods: This is a multicenter, randomized, evaluator-blinded study of endurance exercise training. The exercise intervention will be delivered by treadmill at 2 doses over 18 months: moderate intensity (4 days/week for 30 min per session at 60-65% maximum heart rate) and high intensity (4 days/week for 30 min per session at 80-85% maximum heart rate). We will randomize 370 participants and follow them at multiple time points for 24 months. The primary outcome is the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score (Part III) with the primary analysis assessing the change in MDS-UPDRS motor score (Part III) over 12 months, or until initiation of symptomatic antiparkinsonian treatment if before 12 months. Secondary outcomes are striatal dopamine transporter binding, 6-min walk distance, number of daily steps, cognitive function, physical fitness, quality of life, time to initiate dopaminergic medication, circulating levels of C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF). Tertiary outcomes are walking stride length and turning velocity. Discussion: SPARX3 is a Phase 3 clinical trial designed to determine the efficacy of high-intensity, endurance treadmill exercise to slow the progression of PD as measured by the MDS-UPDRS motor score. Establishing whether high-intensity endurance treadmill exercise can slow the progression of PD would mark a significant breakthrough in treating PD. It would have a meaningful impact on the quality of life of people with PD, their caregivers and public health.Item The Commercial Genetic Testing Landscape for Parkinson’s Disease(Elsevier, 2021) Cook, Lola; Schulze, Jeanine; Verbrugge, Jennifer; Beck, James C.; Marder, Karen S.; Saunders-Pullman, Rachel; Klein, Christine; Naito, Anna; Alcalay, Roy N.; ClinGen Parkinson’s Disease Gene Curation Expert Panel; MDS Task Force for Recommendations for Genetic Testing in Parkinson’s Disease; Medical and Molecular Genetics, School of MedicineIntroduction: There have been no specific guidelines regarding which genes should be tested in the clinical setting for Parkinson's disease (PD) or parkinsonism. We evaluated the types of clinical genetic testing offered for PD as the first step of our gene curation. Methods: The National Institutes of Health (NIH) Genetic Testing Registry (GTR) was queried on 12/7/2020 to identify current commercial PD genetic test offerings by clinical laboratories, internationally. Results: We identified 502 unique clinical genetic tests for PD, from 28 Clinical Laboratory Improvement Amendments (CLIA)-approved clinical laboratories. These included 11 diagnostic PD panels. The panels were notable for their differences in size, ranging from 5 to 62 genes. Five genes for variant query were included in all panels (SNCA, PRKN, PINK-1, PARK7 (DJ1), and LRRK2). Notably, the addition of the VPS35 and GBA genes was variable. Panel size differences stemmed from inclusion of genes linked to atypical parkinsonism and dystonia disorders, and genes in which the link to PD causation is controversial. Conclusion: There is an urgent need for expert opinion regarding which genes should be included in a commercial laboratory multi-gene panel for PD.