Targeting Parkinson's Disease

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8:00-9:00 am Morning Coffee, Pre-Conference Short Course & Symposia Registration

Program Scientific Advisor: Susan E. Browne, Ph.D., Director, Neuropharmacology, Merck Research Labs


9:00 Chairperson’s Remarks

Susan E. Browne, Ph.D., Director, Neuropharmacology, Merck Research Labs

9:05 The Discovery and Development of Positive Allosteric Modulators of mGlu4 for the Treatment of Parkinson’s Disease

Corey R. Hopkins, Ph.D., Research Assistant Professor, Associate Director, Medicinal Chemistry, Drug Discovery Program, Vanderbilt

9:35 Sirt1 Protects Against a-Synuclein Aggregation by Activating Molecular Chaperonesbio

Gizem Donmez, Ph.D., Assistant Professor, Neuroscience, Tufts University School of Medicine

We show that the lifespan of a mouse model with A53T α-synuclein mutation is increased by overexpressing SIRT1 and decreased by knocking out SIRT1 in brain. Further, α-synuclein aggregates are reduced in the brains of mice with SIRT1 overexpression, and increased by SIRT1 deletion. We show that SIRT1 deacetylates heat shock factor 1 (HSF1) and increases HSP70 RNA and protein levels, but only in the brains of mice with A53T and SIRT1 expression. Thus SIRT1 responds to α-synuclein aggregation-induced stress by activating molecular chaperones to protect against disease.

10:05 Glucocerebrosidase Associated Synucleinopathies: Potential Mechanisms

Grisel Lopez, M.D., Senior Staff Clinician, National Human Genome Research Institute, Section on Molecular Neurogenetics, Medical Genetics Branch, NIH

Mutations in the glucocerebrosidase gene (GBA) are the most common genetic risk factor for PD identified to date. The odds ratio for any GBA mutation in patients with PD is greater than 5. GBA encodes for the enzyme glucocerebrosidase. A subset of subjecs with at least one GBA mutation develop parkinsonism. The pathological mechanisms are not completely understood, but could be related alpha-synuclein processing. Theories proposed to explain this association will be discussed.

10:30 Coffee Break


10:45 Novel Tools for LRRK2 Research

Sonal S. Das, Ph.D., Associate Director, Research Programs, The Michael J. Fox Foundation for Parkinson’s Research

Mutations in LRRK2 represent the most frequently found genetic factors yet discovered for PD and its role as a putative kinase, combined with the fact that disease-associated mutations appear to enhance this activity, make it is an attractive target for therapeutic development. Given the unanswered questions surrounding basic biological aspects of LRRK2 function, MJFF has endeavored to generate, characterize and distribute those tools, including antibodies, assays, viral vectors and animal models, that will assist investigators in their pursuit of understanding how LRRK2 function is dysregulated in PD.

11:15 Targeting LRRK2 for Parkinson’s Disease Pathogenesis and Therapeutics

Wanli W. Smith, M.D., Ph.D., Assistant Professor, Head, Molecular Neuroscience Laboratory, Pharmaceutical Sciences, University of Maryland School of Pharmacy

We have found a number of positive compounds can reduce mutant LRRK2-induced neuronal degeneration in mouse primary neuronal cultures. Moreover one of these compounds can attenuate PD-like phenotypes in a LRRK2 Drosophila model, including increasing survival, improving locomotor impairment and reducing the loss of dopaminergic neurons. These findings suggest that these novel compounds targeting LRRK2 not only provide the useful probes for LRRK2-linked pathogenesis studies but also provide potential candidates for PD intervention.

11:45 The Challenges of LRRK2 as a Therapeutic Target

Warren Hirst, Ph.D., Associate Research Fellow, Neurodegeneration, Pfizer

Genetic mutations in Leucine Rich Repeat Kinase 2 (LRRK2) have been linked to a form of autosomal dominant Parkinson’s disease (PD). One of the most prevalent mutations, G2019S, results in increased LRRK2 kinase activity, which is believed to play a major role in the etiology of PD. . Despite challenges, we, and others, are developing LRRK2 kinase inhibitors which will be critical to increase our understanding of LRRK2 function and may potentially be developed into novel therapeutics for PD.

12:15 pm Enjoy Lunch on Your Own


1:40 Chairperson’s Remarks

Kuldip Dave, Ph.D., Associate Director, Research Programs, The Michael J. Fox Foundation for Parkinson’s Research

2:00 Exploring the Potential of Modified Release Aminoadamantanes in Parkinson’s Disease and Related Indications

Gregory Went, Ph.D., CEO & Chairman, Adamas Pharmaceuticals

2:30 Progress on Allosteric Modulation of mGluR5 and mGluR4: Towards New Treatment Paradigms in Parkinson’s Disease

Sonia-Maria Poli, Ph.D., Head, NCD and CNS programs, NCD, Addex Pharmaceuticals

Allosteric modulation is a unique opportunity to address undruggable targets of high therapeutic value for Parkinson’s disease and other indications mGluR5 negative allosteric modulation is a clinically proven mechanism for PD-LID. Examples of preclinical and clinical validation will be presented, including data on dipraglurant, a proprietary Addex compound in PhIIa testing for PD-LID. New targets relevant for PD treatment and accessible through allosteric modulation will be discussed (e.g. TrKB)

3:00 Targeting G Protein-Coupled Receptor Kinases to Combat Runaway Dopamine Receptor Signaling in L-DOPA-Induced Dyskinesia

Eugenia Gurevich, Ph.D., Associate Professor, Pharmacology, Vanderbilt University

The talk will discuss the role of G protein-coupled receptor kinases (GRKs), the key proteins mediating desensitization of G protein-coupled receptors, in regulating the signaling via dopamine receptors in the dopamine-depleted striatum and during L-DOPA therapy. We will show how specific functions of GRKs can be used to alleviate LID while enhancing the antiparkinsonian effect of L-DOPA, thus achieving an elusive goal of controlling both LID and motor fluctuations.

3:30 Refreshment Break

» 3:45 KEYNOTE ADDRESS: Repositioning Drugs for Parkinson’s Disease

Kuldip Dave, Ph.D., Associate Director, Research Programs, The Michael J. Fox Foundation for Parkinson’s Research

Drug repositioning refers to applying an existing compound (either an approved drug or a clinical candidate in testing) for one indication to another indication and offers several advantages over traditional drug discovery: reduced cost, risk and time to market. This talk will describe the initiatives undertaken by the Michael J. Fox Foundation for Parkinson’s research, in identifying and funding the repositioning of clinically safe compounds from other indications to Parkinson’s disease.

4:15 EXPERT PANEL: Next Steps in Parkinson’s Disease Research?

Moderator: Susan E. Browne, Ph.D., Director, Neuropharmacology, Merck Research Labs

What can we do to improve better translation from pre-clinical models to human trials?
Drug repositioning vs. drug discovery
What targets should we be looking at next?

5:00 End of Day


7:15 am Morning Coffee


8:00 Chairperson’s Opening Remarks

Marcelle Bergeron, Ph.D., Director, Neuropharmacology, Elan Pharmaceuticals

8:10 Talk Title to be Announced

Marcelle Bergeron, Ph.D., Director, Neuropharmacology, Elan Pharmaceuticals

8:40 Hunting for IgG Biomarkers for Alzheimer’s

Dwight German, Ph.D., Professor, Department of Psychiatry, University of Texas Southwestern Medical Center

Using a 15,000 peptoid library, we have identified 3 Alzheimer’s disease (AD)-related peptoids that capture markedly elevated serum IgGs compared to those found in normal controls and those with Parkinson’s disease. These peptoids also appear to be useful for the identification of the early stage of AD, i.e., mild cognitive impairment. Future studies will further validate these biomarkers, and identify the antigens that are recognized by the IgG antibodies

9:10 Sponsored Presentations (Opportunities Available)

9:40 Surgery and Anesthesia as Modifiers of Alzheimer’s Trajectory

Roderic G. Eckenhoff, M.D., Vice Chair for Research, Austin Lamont Professor of Anesthesiology & Critical Care, Perelman School of Medicine, University of Pennsylvania

Modern healthcare involves operative procedures that produce considerable stress, pain and inflammation. These procedures occur more frequent in the elderly, and are often followed by cognitive decline which is occasionally irreversible and associated with excess morbidity and mortality. Recent work has suggested that the trajectory of incipient Alzheimer pathology may be accelerated by features of the perioperative period, such as anesthetics or inflammation. I will summarize evidence from both pre-clinical and clinical studies, and point to the essential role for reliable biomarkers.

10:10 End of Symposium

4 Jun - 4 Jun 2012
United States of America
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