Diabetes Drug May Slow Progression of Parkinson’s Disease

MedicalResearch.com Interview with:

Patrik Brundin, M.D., Ph.D. Director, Center for Neurodegenerative Science Van Andel Research Institute

Dr. Patrik Brundin

Patrik Brundin, M.D., Ph.D.
Director, Center for Neurodegenerative Science
Van Andel Research Institute

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The investigational drug at the heart of our study, MSDC-0160, has been in development to treat type 2 diabetes by improving cellular metabolism.

In Parkinson’s, reductions in cellular metabolism slow down vital housekeeping processes that clear out toxic proteins that otherwise accumulate with age. If these proteins aren’t removed, they clump together, leading to the damage and cell death that causes Parkinson’s hallmark symptoms, such as rigidity and tremor. MSDC-0160 helps keep these housekeeping processes working, ultimately protecting the brain.

We demonstrated that MSDC-0160 has strong, reproducible, positive effects across multiple models of Parkinson’s disease—it rescued dopamine-producing cells, improved behavioral deficits in mouse models and reversed inflammation. Overall, we believe it is a strong candidate for repurposing as a potential treatment that actually may slow the disease’s progression, rather than only mitigating symptoms.

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Deep Brain Stimulation Improves Parkinson’s Symptoms In Some Patients With SPG 11 Mutations

MedicalResearch.com Interview with:

Adolfo Ramirez Zamora, MD Associate Professor of Neurology and Phyllis E. Dake Endowed Chair in Movement Disorders Department of Neurology Albany Medical College

Dr. Adolfo Ramirez Zamora

Adolfo Ramirez Zamora, MD
Associate Professor of Neurology and
Phyllis E. Dake Endowed Chair in Movement Disorders
Department of Neurology
Albany Medical College

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Patients with SPG 11 mutations can present with motor symptoms characterized by juvenile onset dystonia, Parkinsonism and lower extremity spasticity. Parkinsonism appears to be responsive to levodopa therapy early in the disease but treatment is complicated by the occurrence of motor fluctuations resembling parkinson disease. Patients have short duration of medication effects, unpredictable response to medications along with generalized, excessive involuntary movements known as dyskinesias.

Deep Brain stimulation is a well-established treatment for movement disorders but it has never been used in this disease. We first report the clinical outcome obtained with globus pallidus internal deep brain stimulation in a patient with parkinsonism, dystonia, dyskinesias related to SPG 11. Additionally, we report for the first time the basal ganglia changes observed in the disease using intraoperative neuronal recordings. Patient had a sustained and remarkable response to stimulation over the next two years without side effects. Neurophysiologic changes revealed a unique pattern of neuronal firing despite of the resemblance to advance Parkinsons disease.

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Single Head Injury Linked To Parkinson’s but Not Alzheimer’s Disease

MedicalResearch.com Interview with:

Paul K. Crane, MD MPH Professor Department of Medicine Adjunct Professor Department of Health Services University of Washington

Dr. Paul Crane

Paul K. Crane, MD MPH Professor
Department of Medicine Adjunct Professor
Department of Health Services
University of Washington

MedicalResearch.com: What is the background for this study?

Response: The background is that the most common experience of head injury with loss of consciousness is an apparent recovery. Sometimes this is very fast, sometimes it takes somewhat longer, but typically people return to their prior baseline. Nevertheless there is concern that the head injury may have set in motion processes that would lead to late life neurodegenerative conditions. This is bad enough for someone to deal with but it’s made even worse if the head injury isn’t even the victim’s fault. Previous research has focused especially on Alzheimer’s disease. A more limited research has focused on Parkinson’s disease.

We used data from three prospective cohort studies that included more than 7,000 people to study the relationship between head injury with loss of consciousness and subsequent risk of Alzheimer’s and Parkinson’s disease. We collected head injury exposure data at study enrollment, at a time when we administered cognitive tests and knew they did not have dementia, so our exposure data are not biased. Each of these studies also performed brain autopsies on people who died, and we evaluated data from more than 1500 autopsies.

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Rosacea Should Be Considered More Than Cosmetic Disorder

MedicalResearch.com Interview with:

Alexander Egeberg, MD PhD National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology Herlev and Gentofte University Hospital, University of Copenhagen Hellerup, Denmark

Dr. Alexander Egeberg

Alexander Egeberg, MD PhD
National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology
Herlev and Gentofte University Hospital
University of Copenhagen
Hellerup, Denmark 

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Egeberg: Rosacea skin shows an up-regulation of various cytokines (small proteins that are important in cell signalling), and displays increased activation and expression of matrix metalloproteinases (MMPs). Both rosacea and Parkinson’s disease have been associated with small intestinal bacterial overgrowth and Helicobacter pylori infection, and MMPs. MMPs are enzymes that are involved in tissue remodeling, organ development, and regulation of inflammatory processes.

Parkinson’s is a progressive neurological disease that results from the gradual loss of brain cells that produce dopamine, a chemical that sends messages to the part of the brain that controls movement and coordination. Importantly, MMPs have also been implicated in the pathogenesis of Parkinson’s disease and other neurodegenerative disorders, and MMPs contribute to loss of dopamine producing brain cells.

Rosacea is often characterized by flare-ups and remissions and typically presents as a redness on the cheeks, nose, chin or forehead. In our study, we found a significantly (approximately two-fold) increased risk of developing Parkinson’s disease, a chronic and progressive movement disorder, among patients with rosacea. Also, we found that treatment with tetracycline, an oral antibiotic, was associated with a slightly decreased risk of Parkinson’s disease.

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Selective Targeting Can Improve Deep Brain Stimulation For Parkinson’s

Dr. Ilse S. Pienaar Honorary Lecturer in Neuroscience at Imperial College London (& Snr. Lecturer in Cellular Pathology, Northumbria University) Centre for Neuroinflammation & Neurodegeneration Division of Brain Sciences Faculty of Medicine Imperial College London Hammersmith Hospital Campus London United KingdomMedicalResearch.com Interview with:
Dr. Ilse S. Pienaar

Honorary Lecturer in Neuroscience at Imperial College London
(& Snr. Lecturer in Cellular Pathology, Northumbria University)
Centre for Neuroinflammation & Neurodegeneration
Division of Brain Sciences Faculty of Medicine
Imperial College London
Hammersmith Hospital Campus
London United Kingdom

 

Medical Research: What is the background for this study? What are the main findings?

Dr. Pienaar: A highly heterogeneous brainstem structure, the pedunculopontine nucleus (PPN) has been deemed a promising target for the delivery of deep-brain stimulation (DBS), to alleviate aspects of Parkinson’s disease (PD), especially gait and postural instability. However, optimal therapeutic targeting of the PPN has been hampered due to DBS being unable to discriminate between cell types being targeted. We optomised a novel technique, Designer Receptors Exclusively Activated by Designer Drugs (DREADD) in a rat model of PD, by which to target only the PPN cholinergic neurons. A series of behavioral tests revealed that selective stimulation of the PPN cholinergics completely reverses gait problems and postural instability in the PD rats.

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Paring Easy Aerobics With Fast Paced Cognitive Tasks May Improve Exercise Intensity

Dr. Lori P. Altmann Department of Speech, Language, and Hearing Sciences Center for Movement Disorders and Neurorestoration University of Florida, Gainesville, FloridaMedicalResearch.com Interview with:
Dr. Lori P. Altmann
Department of Speech, Language, and Hearing Sciences
Center for Movement Disorders and Neurorestoration
University of Florida, Gainesville, Florida

Medical Research: What is the background for this study? What are the main findings?

Dr. Altmann: There are a multitude of studies from our labs and others examining the effects of doing a variety of different cognitive tasks while walking or while maintaining postural control, and the results across studies are consistent—motor performance usually declines.  These “dual task effects” are exaggerated in healthy older adults, and are even more pronounced in people with Parkinson disease (PD).  Our study investigated dual task effects during cycling in healthy older adults and people with Parkinson disease.  In contrast to most studies of this type which typically contrast dual task effects of two cognitive tasks, we used an array of 12 cognitive tasks of graded difficulty, from very very easy to extremely difficult.  One of our primary goals was to establish that the dual task effects were directly related to the difficulty of the cognitive task.

Our primary findings were that, instead of cycling slower when doing various cognitive task, both groups of participants sped up, and the amount they sped up was directly related to the difficulty of cognitive tasks.  In the easiest task, cycling speed increased by an average of about 25%, With some participants actually doubling their single task speed. There was no evidence that this increase in cycling speed came as a result of prioritizing cycling over the cognitive tasks, as scores on the cognitive tasks either remained the same or got slightly better.  Interestingly, people with Parkinson disease still showed faster cycling during the easiest tasks, but did not benefit as much from the dual task as the healthy adults.

We attribute our findings to arousal that is triggered by both the cycling and the cognitive tasks which increases attentional resources that can be used for both motor and cognitive processing.  We believe the findings haven’t been documented before because most studies use gait or balance as the motor tasks, and these are much more difficult tasks that demand more attentional resources, leading to the typical findings of dual task costs instead of dual task benefits. The decrease in dual task benefits experienced by people with Parkinson disease, we believe, is due to the effects of Parkinson disease on neurotransmitters.  Both cognitive and physiological arousal increase the production of dopamine and norepinephrine in the brain, and disease processes in Parkinson disease interfere with production of these neurotransmitters, thus limiting arousal-based increases in attentional resources.

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MAPT locus on Chromosome 17 Links Parkinson’s and Alzheimer’s Diseases

Dr. Rahul S. Desikan MD, PhD Department of Radiologoy University of California, San Diego School of MedicineMedicalResearch.com Interview with:
Dr. Rahul S. Desikan MD, PhD
Department of Radiologoy
University of California, San Diego School of Medicine

Medical Research: What is the background for this study? What are the main findings?

Dr. Desikan: The MAPT gene encodes the tau protein, which plays an integral role in Alzheimer’s disease (AD) neurodegeneration. Though a number of studies have investigated this issue, the role of the MAPT gene in Alzheimer’s disease is still unclear. In contrast, a number of studies have found a robust association between MAPT and increased risk for other ‘tauopathies’ like Parkinson’s disease (PD). In our study, rather than evaluating all possible genetic loci, we only assessed shared genetic variants between Alzheimer’s disease and PD. By using this type of approach, we were able to increase our statistical power for gene discovery in Alzheimer’s disease.

We found genetic overlap between Alzheimer’s disease and Parkinson’s disease at a locus on chromosome 17 within the MAPT region. Our findings demonstrate that this MAPT associated locus increases risk for Alzheimer’s disease, correlates with gene expression of MAPT and is associated with brain atrophy of the entorhinal cortex and hippocampus on longitudinal MRI scans.

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Parkinson’s Disease: Are Newer Meds Better Than Levodopa?

Richard Gray Professor of Medical Statistics Clinical Trial Service Unit Richard Doll Building, OxfordMedicalResearch Interview with:
Richard Gray
Professor of Medical Statistics
Clinical Trial Service Unit
Richard Doll Building, Oxford


MedicalResearch: What are the main findings of the study?

Prof. Gray: We found that, when we asked patients with Parkinson’s disease how their drugs affected their overall quality of life, the older drug levodopa was better than newer, more expensive drugs and that this benefit persisted for at least seven years from starting treatment.
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Dementia: Lewy Body vs Parkinson’s Disease

Rodolfo Savica, MD, MSc Department of Neurology, College of Medicine Division of Epidemiology, Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, MinnesotaMedicalResearch.com Interview with:
Rodolfo Savica, MD, MSc
Department of Neurology, College of Medicine
Division of Epidemiology, Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota

 

MedicalResearch.com: What are the main findings of this study?

Dr. Savica: This study is the first in North America to explore the incidence of DLB and PDD in a population based sample. We found that the overall incidence of dementia with Lewy bodies (DLB), considered the second leading cause of neurodegenerative dementia after Alzheimer`s disease, is lower than that of Parkinson`s disease (PD), increases steeply with age, and is markedly higher in men than in women.
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