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Michael J Fox Foundation

Daryl J Wile, Pankaj A Agarwal, Michael Schulzer, Edwin Mak, Katherine Dinelle, Elham Shahinfard, Nasim Vafai, Kazuko Hasegawa, Jing Zhang, Jessamyn McKenzie, Nicole Neilson, Audrey Strongosky, Ryan J Uitti, Mark Guttman, Cyrus P Zabetian, Yu-Shin Ding, Mike Adam, Jan Aasly, Zbigniew K Wszolek, Matthew Farrer, Vesna Sossi, A Jon Stoessl
BACKGROUND: People with Parkinson's disease can show premotor neurochemical changes in the dopaminergic and non-dopaminergic systems. Using PET, we assessed whether dopaminergic and serotonin transporter changes are similar in LRRK2 mutation carriers with Parkinson's disease and individuals with sporadic Parkinson's disease, and whether LRRK2 mutation carriers without motor symptoms show PET changes. METHODS: We did two cross-sectional PET studies at the Pacific Parkinson's Research Centre in Vancouver, BC, Canada...
May 2017: Lancet Neurology
John M Lee, Pascal Derkinderen, Jeffrey H Kordower, Roy Freeman, David G Munoz, Thomas Kremer, Wagner Zago, Samantha J Hutten, Charles H Adler, Geidy E Serrano, Thomas G Beach
The neuropathological hallmark of Parkinson disease (PD) is abnormal accumulation of α-synuclein (α-syn). Demonstrating pathological α-syn in live patients would be useful for identifying and monitoring PD patients. To date, however, imaging and biofluid approaches have not permitted premortem assessment of pathological α-syn. α-syn pathology in the peripheral nervous system of patients with PD has been demonstrated in studies dating back more than 40 years. More recent work suggests that colon, submandibular gland and skin biopsies could be useful as expedient biomarkers but histological differentiation of pathological and normal peripheral α-syn has been challenging and multiple research groups have reported variable results...
January 1, 2017: Journal of Neuropathology and Experimental Neurology
Lauren Heusinkveld, Mallory Hacker, Maxim Turchan, Madelyn Bollig, Christina Tamargo, William Fisher, Lauren McLaughlin, Adria Martig, David Charles
The FDA has approved a multicenter, double-blind, Phase III, pivotal trial testing deep brain stimulation (DBS) in 280 people with very early stage Parkinson's disease (PD; IDE#G050016). In partnership with The Michael J. Fox Foundation for Parkinson's Research, we conducted a survey to investigate motivating factors, barriers, and gender differences among potentially eligible patients for participation in a trial testing DBS in early PD compared to standard medical treatment. The majority of survey respondents (72%) indicated they would consider learning more about participating...
2017: Journal of Parkinson's Disease
Joanne Trinh, Emil K Gustavsson, Carles Vilariño-Güell, Stephanie Bortnick, Jeanne Latourelle, Marna B McKenzie, Chelsea Szu Tu, Ekaterina Nosova, Jaskaran Khinda, Austen Milnerwood, Suzanne Lesage, Alexis Brice, Meriem Tazir, Jan O Aasly, Laura Parkkinen, Hazal Haytural, Tatiana Foroud, Richard H Myers, Samia Ben Sassi, Emna Hentati, Fatma Nabli, Emna Farhat, Rim Amouri, Fayçal Hentati, Matthew J Farrer
BACKGROUND: Leucine-rich repeat kinase 2 (LRRK2) mutation 6055G→A (Gly2019Ser) accounts for roughly 1% of patients with Parkinson's disease in white populations, 13-30% in Ashkenazi Jewish populations, and 30-40% in North African Arab-Berber populations, although age of onset is variable. Some carriers have early-onset parkinsonism, whereas others remain asymptomatic despite advanced age. We aimed to use a genome-wide approach to identify genetic variability that directly affects LRRK2 Gly2019Ser penetrance...
November 2016: Lancet Neurology
Balint Otvos, Daniel J Silver, Erin E Mulkearns-Hubert, Alvaro G Alvarado, Soumya M Turaga, Mia D Sorensen, Patricia Rayman, William A Flavahan, James S Hale, Kevin Stoltz, Maksim Sinyuk, Qiulian Wu, Awad Jarrar, Sung-Hak Kim, Paul L Fox, Ichiro Nakano, Jeremy N Rich, Richard M Ransohoff, James Finke, Bjarne W Kristensen, Michael A Vogelbaum, Justin D Lathia
Shifting the balance away from tumor-mediated immune suppression toward tumor immune rejection is the conceptual foundation for a variety of immunotherapy efforts currently being tested. These efforts largely focus on activating antitumor immune responses but are confounded by multiple immune cell populations, including myeloid-derived suppressor cells (MDSCs), which serve to suppress immune system function. We have identified immune-suppressive MDSCs in the brains of GBM patients and found that they were in close proximity to self-renewing cancer stem cells (CSCs)...
August 2016: Stem Cells
Un Jung Kang, Jennifer G Goldman, Roy N Alcalay, Tao Xie, Paul Tuite, Claire Henchcliffe, Penelope Hogarth, Amy W Amara, Samuel Frank, Alice Rudolph, Cynthia Casaceli, Howard Andrews, Katrina Gwinn, Margaret Sutherland, Catherine Kopil, Lona Vincent, Mark Frasier
BACKGROUND: Identifying PD-specific biomarkers in biofluids will greatly aid in diagnosis, monitoring progression, and therapeutic interventions. PD biomarkers have been limited by poor discriminatory power, partly driven by heterogeneity of the disease, variability of collection protocols, and focus on de novo, unmedicated patients. Thus, a platform for biomarker discovery and validation in well-characterized, clinically typical, moderate to advanced PD cohorts is critically needed. METHODS: BioFIND (Fox Investigation for New Discovery of Biomarkers in Parkinson's Disease) is a cross-sectional, multicenter biomarker study that established a repository of clinical data, blood, DNA, RNA, CSF, saliva, and urine samples from 118 moderate to advanced PD and 88 healthy control subjects...
June 2016: Movement Disorders: Official Journal of the Movement Disorder Society
Dolores Vilas, Leslie M Shaw, Peggy Taylor, Daniela Berg, Kathrin Brockmann, Jan Aasly, Connie Marras, Claustre Pont-Sunyer, José Ríos, Ken Marek, Eduardo Tolosa
BACKGROUND: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of inherited Parkinson's disease (PD). Nonmanifesting carriers of LRRK2 mutations are at high risk for developing PD. Information available on cerebrospinal fluid (CSF) biomarkers in LRRK2 carriers remains preliminary. OBJECTIVES: To measure CSF levels of α-synuclein, β amyloid1-42 , total-tau, and phospho-tau181 , in LRRK2-associated PD, idiopathic PD, nonmanifesting carriers, and first-degree relatives of LRRK2-associated PD patients without the mutation (nonmanifesting noncarriers)...
June 2016: Movement Disorders: Official Journal of the Movement Disorder Society
Eric M Thompson, Thomas Hielscher, Eric Bouffet, Marc Remke, Betty Luu, Sridharan Gururangan, Roger E McLendon, Darell D Bigner, Eric S Lipp, Sebastien Perreault, Yoon-Jae Cho, Gerald Grant, Seung-Ki Kim, Ji Yeoun Lee, Amulya A Nageswara Rao, Caterina Giannini, Kay Ka Wai Li, Ho-Keung Ng, Yu Yao, Toshihiro Kumabe, Teiji Tominaga, Wieslawa A Grajkowska, Marta Perek-Polnik, David C Y Low, Wan Tew Seow, Kenneth T E Chang, Jaume Mora, Ian F Pollack, Ronald L Hamilton, Sarah Leary, Andrew S Moore, Wendy J Ingram, Andrew R Hallahan, Anne Jouvet, Michelle Fèvre-Montange, Alexandre Vasiljevic, Cecile Faure-Conter, Tomoko Shofuda, Naoki Kagawa, Naoya Hashimoto, Nada Jabado, Alexander G Weil, Tenzin Gayden, Takafumi Wataya, Tarek Shalaby, Michael Grotzer, Karel Zitterbart, Jaroslav Sterba, Leos Kren, Tibor Hortobágyi, Almos Klekner, Bognár László, Tímea Pócza, Peter Hauser, Ulrich Schüller, Shin Jung, Woo-Youl Jang, Pim J French, Johan M Kros, Marie-Lise C van Veelen, Luca Massimi, Jeffrey R Leonard, Joshua B Rubin, Rajeev Vibhakar, Lola B Chambless, Michael K Cooper, Reid C Thompson, Claudia C Faria, Alice Carvalho, Sofia Nunes, José Pimentel, Xing Fan, Karin M Muraszko, Enrique López-Aguilar, David Lyden, Livia Garzia, David J H Shih, Noriyuki Kijima, Christian Schneider, Jennifer Adamski, Paul A Northcott, Marcel Kool, David T W Jones, Jennifer A Chan, Ana Nikolic, Maria Luisa Garre, Erwin G Van Meir, Satoru Osuka, Jeffrey J Olson, Arman Jahangiri, Brandyn A Castro, Nalin Gupta, William A Weiss, Iska Moxon-Emre, Donald J Mabbott, Alvaro Lassaletta, Cynthia E Hawkins, Uri Tabori, James Drake, Abhaya Kulkarni, Peter Dirks, James T Rutka, Andrey Korshunov, Stefan M Pfister, Roger J Packer, Vijay Ramaswamy, Michael D Taylor
BACKGROUND: Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner. METHODS: We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium...
April 2016: Lancet Oncology
Nicolas Dzamko, Dominic B Rowe, Glenda M Halliday
BACKGROUND: We aimed to determine if peripheral or central inflammatory cytokines are altered in healthy subjects carrying a leucine-rich repeat kinase 2 (LRRK2) G2019S mutation, and thus genetically at risk of Parkinson's disease (PD). We also aimed to identify differences in inflammatory cytokines between LRRK2 G2019S-associated and idiopathic PD once the disease manifests. METHODS: Participants were genetically screened and phenotyped, and biological samples were collected and stored by the Michael J...
June 2016: Movement Disorders: Official Journal of the Movement Disorder Society
Domenick T Zero, Michael T Brennan, Troy E Daniels, Athena Papas, Carol Stewart, Andres Pinto, Ibtisam Al-Hashimi, Mahvash Navazesh, Nelson Rhodus, James Sciubba, Mabi Singh, Ava J Wu, Julie Frantsve-Hawley, Sharon Tracy, Philip C Fox, Theresa Lawrence Ford, Stephen Cohen, Frederick B Vivino, Katherine M Hammitt
BACKGROUND: Salivary dysfunction in Sjögren disease can lead to serious and costly oral health complications. Clinical practice guidelines for caries prevention in Sjögren disease were developed to improve quality and consistency of care. METHODS: A national panel of experts devised clinical questions in a Population, Intervention, Comparison, Outcomes format and included use of fluoride, salivary stimulants, antimicrobial agents, and nonfluoride remineralizing agents...
April 2016: Journal of the American Dental Association
Mike A Nalls, Cory Y McLean, Jacqueline Rick, Shirley Eberly, Samantha J Hutten, Katrina Gwinn, Margaret Sutherland, Maria Martinez, Peter Heutink, Nigel M Williams, John Hardy, Thomas Gasser, Alexis Brice, T Ryan Price, Aude Nicolas, Margaux F Keller, Cliona Molony, J Raphael Gibbs, Alice Chen-Plotkin, Eunran Suh, Christopher Letson, Massimo S Fiandaca, Mark Mapstone, Howard J Federoff, Alastair J Noyce, Huw Morris, Vivianna M Van Deerlin, Daniel Weintraub, Cyrus Zabetian, Dena G Hernandez, Suzanne Lesage, Meghan Mullins, Emily Drabant Conley, Carrie A M Northover, Mark Frasier, Ken Marek, Aaron G Day-Williams, David J Stone, John P A Ioannidis, Andrew B Singleton
BACKGROUND: Accurate diagnosis and early detection of complex diseases, such as Parkinson's disease, has the potential to be of great benefit for researchers and clinical practice. We aimed to create a non-invasive, accurate classification model for the diagnosis of Parkinson's disease, which could serve as a basis for future disease prediction studies in longitudinal cohorts. METHODS: We developed a model for disease classification using data from the Parkinson's Progression Marker Initiative (PPMI) study for 367 patients with Parkinson's disease and phenotypically typical imaging data and 165 controls without neurological disease...
October 2015: Lancet Neurology
Sil Kordes, Michael N Pollak, Aeilko H Zwinderman, Ron A Mathôt, Mariëtte J Weterman, Aart Beeker, Cornelis J Punt, Dick J Richel, Johanna W Wilmink
BACKGROUND: In preclinical work and retrospective population studies, the anti-diabetic drug metformin has been associated with antineoplastic activity and decreased burden of many cancers, including pancreatic cancer. There is therefore interest in the hypothesis that this drug might be repurposed for indications in oncology. We aimed to assess the efficacy of the addition of metformin to a standard systemic therapy in patients with advanced pancreatic cancer, and provide the first report of a clinical trial with a survival endpoint of metformin for an oncological indication...
July 2015: Lancet Oncology
Charlotte Rocker, Lily Cappelletti, Claudia Marshall, Claire C Meunier, Deborah W Brooks, Todd Sherer, Sohini Chowdhury
BACKGROUND: As in other therapeutic areas, clinical studies in Parkinson's disease (PD) face significant recruitment challenges. However, qualitative surveys suggest that individuals with PD are willing to participate in clinical research. The Michael J. Fox Foundation therefore established Fox Trial Finder in 2011 to facilitate connection between PD research teams and volunteers. OBJECTIVE: Characterize the research volunteers (with and without PD) registered on Fox Trial Finder as of June 2014, and the published, recruiting studies to identify trends and highlight gaps between research requirements and available volunteers...
2015: Journal of Parkinson's Disease
Thomas G Beach, Charles H Adler, Lucia I Sue, Geidy Serrano, Holly A Shill, Douglas G Walker, LihFen Lue, Alex E Roher, Brittany N Dugger, Chera Maarouf, Alex C Birdsill, Anthony Intorcia, Megan Saxon-Labelle, Joel Pullen, Alexander Scroggins, Jessica Filon, Sarah Scott, Brittany Hoffman, Angelica Garcia, John N Caviness, Joseph G Hentz, Erika Driver-Dunckley, Sandra A Jacobson, Kathryn J Davis, Christine M Belden, Kathy E Long, Michael Malek-Ahmadi, Jessica J Powell, Lisa D Gale, Lisa R Nicholson, Richard J Caselli, Bryan K Woodruff, Steven Z Rapscak, Geoffrey L Ahern, Jiong Shi, Anna D Burke, Eric M Reiman, Marwan N Sabbagh
The Brain and Body Donation Program (BBDP) at Banner Sun Health Research Institute ( started in 1987 with brain-only donations and currently has banked more than 1600 brains. More than 430 whole-body donations have been received since this service was commenced in 2005. The collective academic output of the BBDP is now described as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Most BBDP subjects are enrolled as cognitively normal volunteers residing in the retirement communities of metropolitan Phoenix, Arizona...
August 2015: Neuropathology: Official Journal of the Japanese Society of Neuropathology
Lorraine Iacovitti, Xiaotao Wei, Jingli Cai, Eric W Kostuk, Ruihe Lin, Alexander Gorodinsky, Philip Roman, Gretchen Kusek, Sonal S Das, Audrey Dufour, Terina N Martinez, Kuldip D Dave
Parkinson disease (PD) is the second leading neurodegenerative disease in the US. As there is no known cause or cure for PD, researchers continue to investigate disease mechanisms and potential new therapies in cell culture and in animal models of PD. In PD, one of the most profoundly affected neuronal populations is the tyrosine hydroxylase (TH)-expressing dopaminergic (DA) neurons of the substantia nigra pars compacta (SNpc). These DA-producing neurons undergo degeneration while neighboring DA-producing cells of the ventral tegmental area (VTA) are largely spared...
2014: PloS One
Emilie Lalonde, Adrian S Ishkanian, Jenna Sykes, Michael Fraser, Helen Ross-Adams, Nicholas Erho, Mark J Dunning, Silvia Halim, Alastair D Lamb, Nathalie C Moon, Gaetano Zafarana, Anne Y Warren, Xianyue Meng, John Thoms, Michal R Grzadkowski, Alejandro Berlin, Cherry L Have, Varune R Ramnarine, Cindy Q Yao, Chad A Malloff, Lucia L Lam, Honglei Xie, Nicholas J Harding, Denise Y F Mak, Kenneth C Chu, Lauren C Chong, Dorota H Sendorek, Christine P'ng, Colin C Collins, Jeremy A Squire, Igor Jurisica, Colin Cooper, Rosalind Eeles, Melania Pintilie, Alan Dal Pra, Elai Davicioni, Wan L Lam, Michael Milosevic, David E Neal, Theodorus van der Kwast, Paul C Boutros, Robert G Bristow
BACKGROUND: Clinical prognostic groupings for localised prostate cancers are imprecise, with 30-50% of patients recurring after image-guided radiotherapy or radical prostatectomy. We aimed to test combined genomic and microenvironmental indices in prostate cancer to improve risk stratification and complement clinical prognostic factors. METHODS: We used DNA-based indices alone or in combination with intra-prostatic hypoxia measurements to develop four prognostic indices in 126 low-risk to intermediate-risk patients (Toronto cohort) who will receive image-guided radiotherapy...
December 2014: Lancet Oncology
Roy N Alcalay, Helen Mejia-Santana, Anat Mirelman, Rachel Saunders-Pullman, Deborah Raymond, Christina Palmese, Elise Caccappolo, Laurie Ozelius, Avi Orr-Urtreger, Lorraine Clark, Nir Giladi, Susan Bressman, Karen Marder
BACKGROUND: Ashkenazi Jewish (AJ) LRRK2 carriers are more likely to manifest the postural instability gait difficulty (PIGD) motor phenotype than non-carriers but perform similarly to non-carriers on cognitive screening tests. OBJECTIVE: To compare the cognitive profiles of AJ with Parkinson's disease (PD) with and without LRRK2 G2019S mutations using a comprehensive neuropsychological battery. METHODS: We administered a neuropsychological battery to PD participants in the Michael J...
February 2015: Parkinsonism & related Disorders
Diana W Shineman, John Alam, Margaret Anderson, Sandra E Black, Aaron J Carman, Jeffrey L Cummings, Penny A Dacks, Joel T Dudley, Donald E Frail, Allan Green, Rachel F Lane, Debra Lappin, Tanya Simuni, Richard G Stefanacci, Todd Sherer, Howard M Fillit
Repurposing Food and Drug Administration (FDA)-approved drugs for a new indication may offer an accelerated pathway for new treatments to patients but is also fraught with significant commercial, regulatory, and reimbursement challenges. The Alzheimer's Drug Discovery Foundation (ADDF) and the Michael J. Fox Foundation for Parkinson's Research (MJFF) convened an advisory panel in October 2013 to understand stakeholder perspectives related to repurposing FDA-approved drugs for neurodegenerative diseases. Here, we present opportunities on how philanthropy, industry, and government can begin to address these challenges, promote policy changes, and develop targeted funding strategies to accelerate the potential of FDA-approved repurposed drugs...
July 2014: Annals of Clinical and Translational Neurology
Jacki Liddle, David Ireland, Simon J McBride, Sandra G Brauer, Leanne M Hall, Hang Ding, Mohan Karunanithi, Paul W Hodges, Deborah Theodoros, Peter A Silburn, Helen J Chenery
BACKGROUND: Lifespace is a multidimensional construct that describes the geographic area in which a person lives and conducts their activities, and reflects mobility, health, and well-being. Traditionally, it has been measured by asking older people to self-report the length and frequency of trips taken and assistance required. Global Positioning System (GPS) sensors on smartphones have been used to measure Lifespace of older people, but not with people with Parkinson's disease (PD). OBJECTIVE: The objective of this study was to investigate whether GPS data collected via smartphones could be used to indicate the Lifespace of people with PD...
2014: JMIR MHealth and UHealth
Bram Rochwerg, Waleed Alhazzani, Anees Sindi, Diane Heels-Ansdell, Lehana Thabane, Alison Fox-Robichaud, Lawrence Mbuagbaw, Wojciech Szczeklik, Fayez Alshamsi, Sultan Altayyar, Wang-Chun Ip, Guowei Li, Michael Wang, Anna Wludarczyk, Qi Zhou, Gordon H Guyatt, Deborah J Cook, Roman Jaeschke, Djillali Annane
BACKGROUND: Fluid resuscitation is the cornerstone of sepsis treatment. However, whether balanced or unbalanced crystalloids or natural or synthetic colloids confer a survival advantage is unclear. PURPOSE: To examine the effect of different resuscitative fluids on mortality in patients with sepsis. DATA SOURCES: MEDLINE, EMBASE, ACP Journal Club, CINAHL, HealthSTAR, the Allied and Complementary Medicine Database, and the Cochrane Central Register of Controlled Trials through March 2014...
September 2, 2014: Annals of Internal Medicine
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