Our clinical research is conducted in the Morton and Gloria Shulman Movement Disorders Clinic and with important support through the Edmond J. Safra Program in Parkinsons Disease and recently the Lily Safra Chair in Movement Disorders.
We are involved in a large number of clinical research trials including pharmacologic studies evaluating a number of drugs at various stages of Parkinson's disease. Several of these trials are in collaboration with the Parkinson Study Group.
The Toronto Western Hospital Movement Disorders Program remains a world leader in the surgical management of Parkinson's disease. Recent studies include evaluation of deep brain stimulation in novel sites or for new indications.
Collaborators in the surgical arm of the program include Drs. Alfonso Fasano and Renato Munhoz in neurology and Drs. Andres Lozano, Moji Hodaie, Suneil Kalia and Bill Hutchison in neurosurgery.
Neuropsychological and imaging evaluations of patients participating in these studies represent an important component of our collaborative research. Additional neurophysiologic studies in surgical patients as well as in other movement disorders are carried out by Dr. Robert Chen.
Clinical trials are very active in the program. Dr. Susan Fox directs a program in clinical neuropharmacology and early proof of principle studies. Dr. Connie Marras has a PhD in clinical epidemiology and is directing a program in this field as it applies to movement disorders.
Neuroimaging is an important component of our program and in addition to magnetic resonance imaging we are actively developing a positron-emission tomography program. Dr. Antonio Strafella directs a very active functional imaging research program using positron emission tomography and fMRI.
Molecular and cell biology and clinical genetics of movement disorders including Parkinson's disease is an areas of expanding interest in collaboration with Drs. Peter St George-Hyslop, Ekaterina Rogaeva and Lorraine Kalia and we continue active work in the field of neuropathology in collaboration with the division of neuropathology at UHN and Dr. Lili-Naz Hazrati.
Finally, we are actively collaborating with Dr. Jonathan Brotchie's laboratory in the study of animal models of movement disorders, particularly levodopa-induced dyskinesias.
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Dr. Anthony E. Lang recognized with 2007 Donald Calne Lectureship (professional)
The lectureship is awarded each year to a distinguished neuroscientist of international reputation, whose work is primarily in the area of Parkinson’s disease. The recipient delivers an annual “state of the illness” lecture to the Parkinson community. This year’s lecture will be given on Friday, January 18, 2008 in Ottawa, in conjunction with the Parkinson’s Disease Research Alliance Meeting.
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Colon may play role in Parkinson's diagnosis
CTV News online
Parkinson's disease is a disorder of the brain, but new research suggests the gut and bowel may play a much bigger role than anyone thought.
Parkinson's is a progressive condition that is characterized by tremors or shaking, and difficulties with walking and co-ordination. While it's unclear what causes the disease, it is characterized by the accumulation of a protein called "alpha-synuclein" in brain cells, which kills the cells.
The disease can't be definitively diagnosed until after a patient's death, when an autopsy can reveal alpha-synuclein. So for living patients, there is no test; most diagnoses are made by taking a thorough history of symptoms.
PTC3 and PTC5 are tripartite Tc (toxin complex) toxins from Photorhabdus luminescens, which consist of the binding component TcdA1, the linker component TcdB2 and the enzyme components TccC3 and TccC5, respectively. While PTC5 ADP-ribosylates Rho proteins at Gln61/63 resulting in constitutive activation of the GTPases, PTC3 ADP-ribosylates actin at Thr148 thereby inducing actin polymerization. Here, we identified amino acids involved in ADP-ribosyltransferase activity of TccC3 and TccC5 and analyzed the substrate specificity of Rho-activating TccC5. We compared the time-dependency of Rho protein activation by PTC5 in HeLa cells with the effects of Escherichia coli cytotoxic necrotizing factor 1 (CNF1), which activates Rho GTPases by deamidation of Gln61/63. Using a luciferase reporter assay, we show that PTC5 and PTC3 stimulated gene transcription via myocardin-related transcription factor A (also called MAL) and AP1. MAL activation by PTC5 involved Rho kinase and formins. Activation of AP1 by PTC5 occurred via two MAP kinase pathways involving ERK and Jun kinase, respectively.
The objective of this study is to clarify the role of (G4C2)n expansions in the etiology of Parkinson disease (PD) in the worldwide multicenter Genetic Epidemiology of Parkinson's Disease (GEO-PD) cohort.
Restless genital syndrome is a rare disorder that can be a source of distress and disability. In patients with PD, restless genital syndrome should be included in the differential diagnosis of genital symptoms and restlessness, along with nonmotor wearing off and akathisia. A detailed clinical history is essential for this diagnosis and treatment with dopamine agonists can provide benefit.
Subthalamic nucleus deep brain stimulation (STN-DBS) has revolutionized the management of disabling motor complications in Parkinson's disease. The EARLYSTIM trial applied this treatment to patients who had been experiencing motor complications for less than three years. STN-DBS significantly improved all primary and secondary outcome measures while best medical therapy failed to provide any improvement at the two-year follow-up time point. On face value these results strongly favor the application of STN-DBS far earlier than is currently applied, when patients are just beginning to experience problems with motor complications. Here we review the application of early DBS and the EARLYSTIM trial from the perspectives of clinical issues, health economics and study design and patient expectation of benefit. We conclude that the most relevant issue is not when to operate but on whom and that early is not always better. © 2014 International Parkinson and Movement Disorder Society.
Genetic analyses of patients with neurodegenerative disorders have identified multiple genes that need to be investigated for the presence of damaging variants. However, mutation analysis by Sanger sequencing is costly and time consuming. We tested the utility of a recently designed semi-custom genome-wide array (NeuroX; Illumina, Inc) tailored to study neurodegenerative diseases (e.g., mutation screening).