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Updates on PD from the latest Udall Center: A conference at Northwestern Memorial Hospital

The Parkinson Alliance/DBS-STN Research Team

In October, 2005, The Parkinson Alliance attended a conference, Parkinson's Disease: New Developments, New Awareness in Chicago, IL. We are excited to share with you the information given from The Northwestern Parkinson's Disease and Movement Disorders Center (National Parkinson Foundation Center of Excellence) and Northwestern Memorial Hospital's Healthy Transitions Program. This was an all day conference that did a great job of presenting information relevant to the Parkinson's patient, carer, as well as for medical professionals. The conference also presented information from multiple vantage points, all of which the Parkinson's patient will come in to contact with throughout the course of their illness.

Part I: The Neurologist/Stem Cell Researcher.

The first speaker was Dr. John Kessler, a neurologist, Chair of the Davee Department of Neurology, and the Director of the Feinberg Neuroscience Institute in Chicago who is also the principle investigator on 4 National Institute of Health grants in the field of stem cell research. His talk was titled, Stem Cell Research in Parkinson's Disease: Today and Future. Dr. Kessler began his talk by describing the different types of stem cells (totipotent, pleuripotent, and multipotent) and that each type will lead to a different final product. He explained that there are many potential uses for stem cells including finding treatment/cures for heart disease, diabetes, kidney disease, hair loss, and disorders of the nervous system. Although very promising in many areas, he cautioned that the use of stem cells is not without medical and political problems. For example, he stated that tissue created by stem cells is treated like any other transplanted tissue in the body and the person receiving the stem cells may be required to take large doses of mediations to prevent the rejection of the tissue by one's body. Additionally, he stated that researchers have not been able to control for genetic mismatches in tissues, for example the donor and host would have to be genetically similar (e.g. both from the South Pacific). Politically the problems are vast, including legal limitations, religious differences, ethical challenges, and general fears about manipulating biology. Dr. Kessler also discussed problems with the current policy regarding stem cell usage. He stated that half or more of the current stem cell lines are not proven embryonic stem cells, the cells have been derived with dated technology, cells that were derived with animal cells cannot be used for humans, and there is a general lack of federal funding for developing new lines of stem cells. Dr. Kessler was well versed in the common objections to stem cell research and convincingly answered some of the religious and more general concerns with this research.

Stem cell research is far from perfect. Dr. Kessler noted that there has been previous research looking at fetal tissue implantation that has not demonstrated very promising results. However, the earlier research has provided useful information for stem cell researchers and encouraged them to continue searching for improved technology, modes of transportation/gene therapy for the cells, and the need for genetic engineering to further tailor the cells for optimal results.
A timeline for stem cell research and clinical usage has not been clearly identified, however, Dr. Kessler indicated that he would be surprised if stem cells would be used in patients with PD within 2 years and also surprised if it wasn't used within 7 years. He presented more promising results with a recent study he sent for publication looking at stem cell use in patients with spinal cord injuries. He stated the study should be published in mid November and showed very promising neuronal growth from both the top and bottom portions in damaged spinal cords of rodents. Typically, the scar tissue related to the spinal cord injury prevents neuron growth at both the top and bottom portions of the injury within the spinal cord. Dr. Kessler injected a specific gel with stem cells into the damaged area of the spinal cord and showed microscopic slides of neuronal regrowth around the scar tissue. His results suggest the possibility of improving feeling, sensation, and movement in areas previously affected by the spinal cord injury. He noted that the neuron growth did not fully repair the spinal cord, nor did the subject have full return of motor functioning, but the rodent was able to have some movement in the lower extremities.

He concluded with the predictions that stem cells will revolutionize treatment for many disorders, including Parkinson's disease. Research will continue on the various types of stem cells and of which he indicated that embryonic stem cells have the most utility. He stated that his vision was to use stem cells to regenerate the central nervous system for various diseases but that the more complicated diseases, such as Alzheimer's disease, likely will not be the first target for this research. He did not indicate where Parkinson's disease would fall in the order of diseases appropriate for treatment with stem cells. However, he noted that the US will continue to do this type of research, as will other countries (e.g. China, Australia) and strongly suggested that this type of research will be very promising.

Part II: The Neurologist.

The second speaker, Dr. Tanya Simuni, an Assistant Professor of Neurology at Northwestern University's Feinberg School of Medicine, Medical Director of the Parkinson's Program at Northwestern, and Residency Program Director at Northwestern gave a talk about the general updates for 2005 regarding Parkinson's disease. Dr. Simuni began by discussing the importance of new treatments for motor and nonmotor symptoms as well as focusing on the quality of life in the PD patient and their support networks. Her first objective was to briefly review the potential neuroprotective treatments available for patients with PD. Sadly, there are no proven neuroprotective treatments, however there are experimental treatments (dopamine agonists, Coenzyme Q10, Rasagiline a new MAO-B antagonist, PRECEPT, Minocycline, Creatine, and Neuroimmunophilin ligands) that have been researched and published in the last few years. The results of these studies are mixed and each study Dr. Simuni mentioned had either design weaknesses (no comparison to placebo), was conducted on animals, or was only preliminary. She indicated that research in this area continues and that there are two large studies, one looking at Coenzyme Q10 (funding should be approved 1/06) and another studying Rasagiline (results coming out the first quarter of 2006) that may help shed light on whether or not patients should be taking these medications and if they are neuroprotective as hypothesized. Dr. Simuni reported that the study on PRECEPT was terminated early due to a lack of efficacy in 800 enrolled patients. Additionally, she indicated that the NIH supported an initiative looking at potential neuroprotective agents and that the results of Creatine, Minocycline, and Neuroimmunophilin will be reported in November of 2005.

Dr. Simuni then moved on to talk about new symptomatic treatment for PD. She noted that several new dopamine agonists will be coming out in 2006, including a Rotigotine patch and injectible apokyn. She noted that there are also pending approvals on sublingual (situated or administered under the tongue) Zydis selegiline, and orally dissolvable Parcopa. Dr. Simuni also discussed three experimental treatment options that have shown treatment for dyskinesias and improvement in motor fluctuations including caffeine (protection is thought to come from the adenosine A2A Antagonist), Sarizotan, and Amantadine/Namenda. She strongly suggested that if patients have concerns or questions about the new treatments that they speak with their doctors about possible benefits and risks in changing their medications.

Dr. Simuni also discussed nonmotor symptoms in PD. The first nonmotor symptom she discussed was cognitive dysfunction, which she stated is the number one unmet need in treating this disease. She reported current prevalence rates, from Emre 2003, of cognitive dysfunction at approximately 40% of patients with PD. Risk factors include advanced age, advanced age at onset of PD, early onset levodopa psychosis, PD severity, and presence of axial symptoms (Emre 2003). She noted that cognitive symptoms may be present from early stages of the disease and typically include what is called a dysexecutive syndrome. According to Dr. Simuni a dysexecutive syndrome includes impaired attention, difficulties with planning, initiating, and sequencing, visuospatial skills, poor verbal fluency, impaired free recall of memory, and personality changes. She discussed that the dementia in PD can be caused by multiple factors including Lewy Bodies as well as the same disease process that causes Alzheimer's disease. Sadly, patients with PD can concurrently have Alzheimer's disease. There are drugs that slow dementia if one does or does not have PD, but at this time there is no miracle drug or cure for dementia. Dr. Simuni then went on to discuss depression in PD. She indicated that the prevalence for depression in PD is approximately 42% as compared to 3-8% in persons without PD. She noted that depression is the most common neuropsychiatric symptom of PD and also a very strong factor impacting quality of life of both the patient and the carer. It is notable that depression seen in PD can be due to medications and can also precede the onset of motor symptoms. She encouraged management of depression with either psychotherapy/counseling or medications, both of which have shown promise for patients with PD. Lastly she discussed sleep disorders in PD. She indicated the prevalence cited in Olanow et al. 2001 and Larsen 2003 was 74-89%. It is very important to evaluate and treat sleep disorders as they can severely disrupt the life of the PD patient (excessive daytime sleepiness, apnea, etc.) as well as suggest the presence of other conditions.

Dr. Simuni concluded her talk by discussing alternative nonmedical/nonFDA approved treatments for PD. She highly stressed the importance of exercise for the patient with PD. She indicated this therapy is not an alternative that instead it is essential for the patient as it improves their function, mood, and cognition. Additionally, animal studies have shown that mice with brain degeneration that underwent vigorous exercise did better than those that did not exercise. Dr. Simuni explained that not everyone can run marathons but there are many exercises that most people can do. She suggested structured routines, with onset a gradual increase of intensity, and encouraged regular but safe exercises. If a patient is concerned about the type of exercise they should or should not do she recommended discussing exercise with their physician. Along with exercise she stressed the importance of good nutrition. Dr. Simuni suggested a balanced diet was important and also acknowledged that people need to be aware of the levodopa protein interactions as well as the unestablished role of natural supplements in regard to PD. She again encouraged people that if they have questions regarding their diet that they consult their physician for guidance and support.

Lastly, Dr. Simuni suggested a comprehensive care model for the PD patient including medical management, education, patient and family support, physical therapy, occupational therapy, nutrition, and social services. She discussed that all of these services are available through their comprehensive treatment program at Northwestern as well as other comprehensive centers. Her recommendations for living better with PD included education about the disease, being a partner in decision making with MDs, exercise, healthy nutrition, and having a positive outlook. The future directions she stated for PD include finding a cure, expanding therapeutic choices, supporting new trials for neuroprotective agents, finding treatments for nonmotor symptoms, and generally improving the quality of life of persons living with PD.

Part III: The Neurosurgeon.

Dr. Joshua Rosenow, director of Functional Neurosurgery at Northwestern University's Feinberg School of Medicine Department of Neurosurgery and at Northwestern Memorial Hospital, whom specializes in movement disorders. Dr. Rosenow's talk was titled, Surgery for Parkinson's Disease: Current Status and Future Prospects. Dr. Rosenow briefly discussed prior surgical options for PD up through Deep Brain Stimulation in the later 80's and early 90's. He spent a considerable amount of time discussing DBS and went through the motor and reduced medication benefits from DBS-STN but also discussed that DBS does not prevent PD and the disease continues to worsen with time regardless of current treatments. Interestingly Dr. Rosenow addressed possible theories for the reason that DBS works but agreed that there is no consensus on exactly how this treatment is efficacious. Dr. Rosenow briefly discussed the continuing debate regarding placement site for DBS (subthalamic nucleus or the globus pallidus interna) and suggested that a VA randomized trial that should come out in 18-24 months may help to differentiate which site has fewer side effects and better outcomes.
Dr. Rosenow also discussed technical advances in treating PD. He showed pictures of a new frame that holds the patient's head in place during surgery that has reportedly been less aversive to patients. He then went on to talk about new targets for stimulation for PD. He indicated that stimulation of the posterior subthalamic area (above and next to the STN) has been evaluated in a small series of studies of PD patients, which showed improvement in various types of tremors. He also discussed motor cortex stimulation, which is a method already in use for improvement of pain. He indicated that motor cortex stimulation theoretically makes sense and would be less invasive than DBS. There is current research with stroke patients that have undergone motor cortex stimulation and were shown to have improvement in motor performance, possible increase in ability to complete activities of daily living, and reduced medications. Dr. Rosenow discussed a study by Canavero in 2002, which documented possible negative side effects (hallucinations) for this stimulation, it is notable that there was a very low number of individuals involved in this study. The challenges for this treatment include an uncertain mechanism of action, uncertain best location for stimulation, unknown parameters for the stimulation, the electrode design, and the difficulty that patients have developed a tolerance to the procedure that requires reprogramming. His points to take home regarding restorative options were that these therapies may be the closest treatment to a cure for PD, it may allow for recreation of normal physiology, it may possibly stop or reverse degeneration of dopaminergic cells, and lastly it may remove the requirement for medications to treat PD. He concluded by discussing the few restorative studies that are ongoing and are showing promising results but will require more research and more time to fully evaluate the efficacy and safety of these therapies.

Part IV: The Advocate.

Last, but certainly not least, our very own Carol Walton, executive director of The Parkinson Alliance, spoke. Carol spoke of all the PD organizations and how they work separately as well as in unity for the advancement of research, funding, education, and general awareness of PD. Carol shared personal stories of traveling to Washington, among many other places, and meeting with various politicians, celebrities, doctors, researchers, and patients in her journey to find a cure and increase support for persons with PD.

Carol spoke of the political efforts she and the Parkinson Alliance have gone through to increase support and unding for Parkinson's disease. It was startling to hear how little funding Parkinson's researchers were initially receiving and very moving to hear how far advocates and PD organizations have come not only in their unity and establishment but in raising awareness and funding for PD. Carol shared personal stories of tracking down politicians and made the point that it is easier to track down a politician if you reside in his/her community than it is to track one down in another state that does not really represent you. Her point was that individuals can be heard and she encouraged others to talk with their political representatives for what they believe in because many politicians will listen. She also encouraged people to be involved personally with research and education as well as in their community to support PD as well as to be supported by others in their community. She indicated that there are many large and small organizations that persons affected by PD can belong to and participate with and invited a local Chicagoan up on stage to briefly talk about local happenings.

Carol also showed a very moving video regarding the Parkinson's Unity Walk that takes place annually in New York City and is "the largest single-day, grassroots awareness and fundraising event for the Parkinson's community." The video was very encouraging about being involved with the PD community and showed many people with different levels of severity of PD making a difference and unifying for this wonderful event. The Unity Walk continues to grow each year and Carol also spoke of a recent benefit concert the night prior to this conference that also grows each year and energizes more and more people affected by PD.

Part V: The End.

I thank Northwestern and all of the wonderful speakers at this conference for continuing to provide education, updates, and awareness regarding PD. Lastly, one of the unadvertised highlights of this conference was the diversity of the audience. All around me were patients (some with very obvious movement difficulties and some who had no obvious signs), spouses, family members, friends, and medical professionals that were all invested in learning more and wanting to gain the most updated information to fight against PD. I highly enjoyed the personal stories at lunch, simply observing the audience and speakers, and lastly for being a participant at this wonderful conference at Northwestern.

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