To: National Desk, Health Reporter

Contact: Holly Barkhymer, 212-509-0995 ext. 242 or hbarkhymer@michaeljfox.org; Todd Sherer, 212-509-0995 ext. 243 or tsherer@michaeljfox.org, both of the Michael J. Fox Foundation

NEW YORK, Nov. 3 /U.S. Newswire/ -- The Michael J. Fox Foundation has awarded $2.3 million in total funding for six research projects under its Dopamine Non-Responsive Symptoms of PD initiative. The funding will drive both increased pre-clinical focus on and expanded clinical development for the range of Parkinson's symptoms that do not respond to existing dopamine replacement therapies.

Parkinson's is best known by the general public as a movement disorder whose cardinal symptoms are resting tremor, slowness of movement and rigidity. PD patients also experience a wide range of lesser-known symptoms, however, many of which are non-motor or autonomic in nature, and which are not responsive to existing dopamine replacement therapies. These include depression, constipation, postural instability and gait, cognitive dysfunction, sleep disorders, fatigue and pain, among others. Many patients report that they are among the most debilitating aspects of the disease.

"The clinical features of Parkinson's that do not respond to dopamine replacement are poorly understood and frequently go untreated - yet little work is currently being done to address them," said Deborah W. Brooks, president and CEO of the Foundation. "We launched our Dopamine Non-Responsive initiative to focus researchers on the pursuit of therapies for these unmet symptomatic needs that rob patients of their quality of life."

Studies on postural instability and gait disorders

Three of the funded studies address postural instability and gait disorders, whose causes are not known and for which there is currently no effective treatment.

Pierre Pollak, PhD, of INSERM - University of Grenoble, France, will work to confirm preliminary studies suggesting that deep brain stimulation (DBS) surgery of the pedunculopontine nucleus (PPN) - a specific brainstem nucleus implicated by previous studies in posture/gait disturbances in Parkinson's disease - may be effective in treating gait disorders. (Traditional DBS of the subthalamic nucleus region of the brain does not treat this symptom.) Dr. Pollak was part of the original team that pioneered DBS surgery.

Chantal Franois, PhD, of INSERM - Hpital de la Salptrire, Paris, also will focus on the PPN in an effort to increase understanding of how it contributes to posture and gait dysfunction. Dr. Franois will conduct behavioral tests and molecular analysis of cholinergic degeneration, a pathological feature of Parkinson's disease, in the PPN of primate PD models. Results of Dr. Franois's work will provide direct evidence for a role of the PPN in postural instability and gait disorders, as well as potentially furnish a preclinical model that can be used to test therapies to treat them.

Lisa Shulman, MD, of the University of Maryland School of Medicine will conduct a clinical trial to evaluate the effectiveness of treadmill training with significant aerobic exercise on gait and mobility. Dr. Shulman's team will also evaluate the effects of these exercise therapies on other non- dopamine-responsive symptoms of Parkinson's, including depression, apathy and fatigue. Positive results from this trial would provide physicians with an optimal exercise regimen to prescribe patients suffering from postural instability and gait disorders, something that does not currently exist.

Studies on depression/apathy, constipation and non- dopaminergic degeneration

Three other studies will examine apathy, constipation and potential PD-related degeneration outside the dopaminergic system.

Hubert Fernandez, MD, of the University of Florida will evaluate depression and apathy/depression, enormous problems that significantly detract from quality of life for PD patients as well as their families and caregivers. Dr. Fernandez will conduct a double-blind, placebo-controlled study to test the effectiveness of repetitive transcranial magnetic stimulation (rTMS) on apathy and depression in 36 PD patients. RTMS, which has shown some efficacy in treating depression in non-PD patients, is a noninvasive method for altering the biochemistry and firing patterns of neurons in the cortex. In this treatment, typically conducted a few minutes a day over the course of several weeks, a physician holds a powerful magnet over the frontal regions of a patient's skull and delivers magnetic pulses.

James Greene, MD, PhD, a neurologist at Emory University, will work with an expert gastroenterologist to address constipation, a painful and difficult symptom that affects innumerable people with Parkinson's. Dr. Greene and colleagues will work to develop a preclinical model that reproduces PD-related constipation. The team will evaluate and conduct molecular analysis of gastric function and colonic motility in four rodent models of PD. Results from this study could uncover novel targets for the development of therapies for PD-related constipation, as well as a preclinical model in which to test them.

Kenneth Marek, MD, of the Institute for Neurodegenerative Disorders is a world leader in the development and validation of neuroimaging markers. Dr. Marek and colleagues will test two novel imaging markers in PD patients - one for the serotonin transporter and one for the norepinephrine transporter. The team seeks to identify and validate critical research tools that could be used to test the emerging hypothesis that PD-related degeneration may be occurring outside the dopaminergic system, and that this degeneration may contribute to the development of dopamine-non-responsive symptoms.

Like all Foundation funding initiatives, Dopamine Non- Responsive Symptoms of PD requires the designation of time- dependent milestones. Continued funding will be dependent upon successful completion of these milestones.

Researcher bios and grant abstracts are available on the Foundation's Web site at http://www.michaeljfox.org.

About The Michael J. Fox Foundation

Founded in 2000, The Michael J. Fox Foundation for Parkinson's Research is dedicated to ensuring the development of a cure for Parkinson's disease within this decade through an aggressively funded research agenda. The Foundation has funded more than $82 million in research to date, either directly or through partnerships.

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/© 2006 U.S. Newswire 202-347-2770/

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