Parasitic Infection With Toxoplasmosis May Be Linked To Parkinson’s & Alzheimer’s Disease

MedicalResearch.com Interview with:

Under a magnification of 900X, this hematoxylin and eosin-stained (H&E) photomicrograph of a brain tissue specimen revealed a case of neurotoxoplasmosis in a patient who had also been diagnosed with multiple myeloma. Note the Toxoplasma gondii tissue cyst, within which bradyzoites could be seen developing. CDC Image

Rima McLeod, M.D., F.A.C.P, F.I.D.S.A
Professor of Ophthalmology and Visual Sciences,Pediatrics (Infectious Diseases), and The College,
Director, Toxoplasmosis Center,
Senior Fellow,Institute of Genomics, Genetics and Systems Biology, Member, Commitees on Immunology, and Molecular Medicine and Pathogenesis,
Member Global Health Center, Affiliate CHeSS;
Attending Physician, Chicago Medicine,
The University of Chicago

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

* One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii.
* Approximately fifteen million of these have congenital toxoplasmosis.
* The parasite interconverts between slow-growing, encysted bradyzoites and rapid-growing tachyzoites.
* In mice, T. gondii creates a chronic intra-neuronal infection and an inflammatory process.
* Mice with acute and chronic infection have alterations in neurotransmitters, memory, seizures, and neurobehavior.
* Some epidemiologic-serologic studies show associations between seropositivity for T. gondii and human neurologic diseases, for example, Parkinson’s and Alzheimer’s diseases.
* Although neurobehavioral disease is associated with seropositivity, causality is unproven.
* Serologic studies of humans with diverse genetics are not optimal to detect strong associations or directionality.
* Epidemiologic associations also do not reveal parasite-modulated gene networks in human brain that could provide insights into how to cure and prevent resultant diseases.
* We need integrative approaches to examine relationships between brain parasitism and other brain diseases, to provide a foundation to identify key pathways and molecules for drug and vaccine design
* To address these problems, we considered two central questions: (i) If chronic brain parasitism associates with other neurologic diseases, what are they? And (ii) Which macromolecular networks are modulated by the parasite in human brain that lead to neuropathology which could underpin and facilitate design of treatments?
* We hypothesized that a systems approach integrating multiple levels of host parasite interactions might resolve these questions.
* To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain.  Continue reading

Diabetes Medication Exenatide Shows Promise In Treating Parkinson’s Disease

MedicalResearch.com Interview with:
Dr Dilan Athauda MRCP
Sobell Department of Motor Neuroscience and Movement Disorders
UCL Institute of Neurology & The National Hospital for Neurology and Neurosurgery
London

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

Response: Exenatide is a synthetic version of a naturally occurring protein – exendin-4 – that was originally discovered by Dr John Eng in the early 1990’s in the saliva of the Gila Monster, a venomous lizard native to the Southwestern United states. He and his team were looking for bio-active peptides in insect and lizard venom that could be useful for people with Type 2 diabetes. They discovered that exendin-4 was extremely similar to a human hormone called Glucagon-like peptide-1 (GLP-1).  In humans, GLP-1 is secreted after you eat a meal to stimulate insulin secretion (and inhibit glucagon production) of which the end result is a lowering of blood sugar. Unfortunately human GLP-1 is rapidly broken down by a circulating enzyme called dipeptidyl peptidase IV (DPP-IV) and its effects only last minutes.

Importantly, it was discovered that exendin-4 is naturally resistant to the actions of this enzyme, meaning it’s effects on blood sugar control lasts much longer in the body.  These properties made it very attractive to people trying to treat people with Type 2 diabetes and following many successful randomised controlled trials of patients with Type 2 diabetes in 2005, exenatide was approved for use as a treatment.  During this time, work led by Nigel Greig’s group at the NIA showed that first evidence that exendin-4 had neuroprotective properties, and could protect neurons from a variety of stresses and could also improve growth and rescue degenerating cells. Over the next few years, various groups used exendin-4 in a variety of animal toxin models of Parkinson’s disease and showed that exendin-4 could halt the progression of Parkinsonism and prevent cell death in these models through beneficial effects on inflammation, mitochondrial function and cell survival.

Based on this encouraging pre-clinical data, Professor Foltynie supervised the first small, “open-label”, human trial of exenatide in patients with Parkinson’s disease.  The team found that patients treated with exenatide for 1 year (in addition to their usual medication) had less decline in their motor symptoms when assessed without their medication compared to the control group (just on their usual medication) and this advantage over the control group was still present 1 year after stopping the exenatide injections.  However, this trial was open-label – patients knew they were getting a (potentially beneficial) experimental therapy and so we couldn’t exclude the fact that placebo effects were explaining some of the results we saw.

As a result of the potentially beneficial results seen in this small open label trial we carried out a double-blind, placebo controlled trial.

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Potential Blood Biomarker Predicts Course of Huntington’s Disease

MedicalResearch.com Interview with:

Dr Edward Wild PhD MRC Clinician Scientist Huntington's Disease Centre UCL Institute of Neurology Honorary Consultant Neurologist National Hospital for Neurology & Neurosurgery, London UK

Dr. Wild

Dr Edward Wild PhD
MRC Clinician Scientist
Huntington’s Disease Centre
UCL Institute of Neurology
Honorary Consultant Neurologist
National Hospital for Neurology & Neurosurgery,
London UK

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

Response: Having a readily accessible and sensitive biomarker, that is representative of ongoing neuropathology, could facilitate therapeutic development for Huntington’s disease. Neurofilament light (NfL) protein is one of the component that makes up the cytoskeleton of neurons. It is released when neuronal damage or death occurs and can be quantified in blood.

MedicalResearch.com: WWhat are the main findings?

Response: We carried out a retrospective cohort analysis of samples from the TRACK-HD study – a multisite longitudinal observational study of HD patients. NfL was quantified in plasma from 298 participants at baseline and follow-up. NfL was significantly higher in HD compared to healthy controls and increased with disease stage. Baseline levels of plasma NfL predicted clinical progression, including cognitive and functional decline, and the rate of global and regional brain atrophy. Premanifest individuals who converted to manifest  Huntington’s disease in the three years of the study had significantly higher levels of plasma NfL at baseline. These associations remained significant after adjustment for the combined interaction of age and CAG, currently the best predictor of age of onset of Huntington’s disease. In a separate cohort, levels of NfL in plasma and CSF were highly correlated.

MedicalResearch.com: What should clinicians and patients take away from your report?

Response: Despite decades of research, no substance in blood has shown any power to predict disease progression of Huntington’s disease. In addition, no substance has been shown to be increased as in premanifest subjects over 10 years from their predicted onset suggesting it may have potential for detecting the earliest signs of HD before overt symptoms manifest.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: We hope that quantifying NfL will be incorporated into all future observational studies of  Huntington’s disease and potentially retrospectively where blood or CSF samples have been banked. We feel it should also be used in current and future clinical trials as an efficacy marker to assess whether a drug is slowing neuronal damage, at the very least as an exploratory end point. 

MedicalResearch.com: Is there anything else you would like to add?

Response: At the moment we do not have enough information for this blood test to be of clinical relevance and prognosis of a patient. A lot more research needs to be done before it could be use on an individual basis in the clinic.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation: Lauren M Byrne, Filipe B Rodrigues, Kaj Blennow, Alexandra Durr, Blair R Leavitt, Raymund A C Roos, Rachael I Scahill, Sarah J Tabrizi, Henrik Zetterberg, Douglas Langbehn, Edward J Wild. Neurofilament light protein in blood as a potential biomarker of neurodegeneration in Huntington’s disease: a retrospective cohort analysisThe Lancet Neurology, 2017; DOI: 10.1016/S1474-4422(17)30124-2

http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(17)30124-2/fulltext

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

 

 

 

Refined Deep Brain Stimulation Turns On ‘As Needed’ To Treat Tremors

MedicalResearch.com Interview with:

Howard Jay Chizeck ScD Professor, Electrical Engineering Adjunct Professor, Bioengineering Co-Director UW Biorobotics Laboratory Graduate Program in Neuroscience UW CoMotion Presidential Innovation Fellow Research Thrust Testbed Co-Leader

Prof. Chizeck

Howard Jay Chizeck ScD
Professor, Electrical Engineering
Adjunct Professor, Bioengineering
Co-Director UW Biorobotics Laboratory
Graduate Program in Neuroscience
UW CoMotion Presidential Innovation Fellow
Research Thrust Testbed Co-Leader

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

Response: Essential Tremor is treated using Deep Brain Stimulation (DBS) in some patients. Current clinical practice involves Deep Brain Stimulation with an “always on” stimulation. This causes extra battery drain, because stimulation is applied when not needed. Also excessive stimulation is not necessarily a good thing,

Our work is aimed at adjusting the stimulation, so that it comes on and turns off only when needed to suppress tremor symptoms.

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Intensive Blood Pressure Reduction and Spot Sign in Intracerebral Hemorrhage

MedicalResearch.com Interview with:
Andrea Morotti, M.D.
Research Fellow in Neurology
Massachusetts General Hospital
Harvard Medical School

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

Response: The CT angiography (CTA) spot sign is a validated marker of Intracerebral Hemorrhage (ICH) expansion and may identify those subjects more likely to benefit from intensive blood pressure reduction.

We observed that less than 20% of ICH patients received a CTA as part of their diagnostic workup in a large, international randomized clinical trial. The performance of the spot sign in predicting ICH growth was suboptimal compared with what was reported in previous studies. Intensive blood pressure reduction did not improve functional outcome in spot sign positive patients.

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Extended-Release Amantadine Reduces Dyskinesia in Parkinson’s Disease

MedicalResearch.com Interview with:
Rajesh Pahwa MD
Department of Neurology
University of Kansas Medical Center, Kansas City, KS,

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

Response: Dyskinesia are one of the major unmet needs in Parkinson Disease patients. At the present time there are no approved medication for dyskinesia, however immediate release amantadine is used in PD patients with dyskinesia. ADS-5102 is a long acting, extended release capsule formulation of amantadine HCl administered once daily at bedtime. This study investigated the safety, efficacy and tolerability of ADS-5102 in Parkinson’s disease (PD) patients with levodopa-induced dyskinesia.

This was a randomized, double-blind, placebo-controlled study of Parkinson’s disease patients with levodopa-induced dyskinesia. In total, 126 patients were randomized to placebo or 274 mg ADS-5102 administered orally at bedtime. ADS-5102 was associated with a significant reduction in dyskinesia at 12 weeks compared with placebo, as measured by the mean change in Unified Dyskinesia Rating Scale (treatment difference, –7.9; P =.0009). OFF time was significantly reduced in ADS-5102 patients compared to placebo (treatment difference -0.9 hours, p=.017).

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Music Making Causes Rapid Neuroplastic Changes in Brain

MedicalResearch.com Interview with:

Bernhard Ross, Ph.D. Rotman Research Institute Baycrest Centre ON, Toronto

Dr. Ross

Bernhard Ross, Ph.D.
Rotman Research Institute
Baycrest Centre
ON, Toronto 

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

Response: We know from previous research that brain function for hearing is more strongly developed in musicians. The effect of a musician’s long-term training leads to a neuroplastic effect where their brain has more neurons involved in auditory processing. These neurons show stronger activity during listening to sound than in non-musicians and these findings strongly encouraged us to study neuroplasticity of the adult brain. We were interested in understanding why the neuroplastic effects of training and learning are so clearly expressed in professional musicians.

The study’s main finding was that actively making sound, by playing a musical instrument, changed brain responses for listening and perception. Most importantly, neuroplastic brain changes occurred very quickly, within one hour of listening and making sound. In contrast, brain changes were observed after days in previous studies that only had participants listening to sounds.

Another finding was that brain responses to hearing a sound are different when a person produces the sound themselves compared to listening to a recorded sound or a sound made by another person. This difference demonstrates that brain networks of intention, movement planning, movement execution, and expectation are involved when making a sound. We compared playing a real instrument with pressing a button for hearing a sound and found larger changes in the brain’s response to actively playing a musical instrument than pressing a button to elicit the same sound.

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Antidepressant May Enhance Drug Delivery to the Brain

MedicalResearch.com Interview with:

Ronald Cannon, Ph.D. Staff scientist at NIH’s National Institute of Environmental Health Sciences

Dr. Cannon

Ronald Cannon, Ph.D.
Staff scientist at NIH’s National Institute of Environmental Health Sciences

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

Response: The protein pump, P-glycoprotein, is a major obstacle to the delivery of therapeutic drugs across the blood-brain barrier and into the central nervous system (CNS). During the last 10 years, our laboratory has studied the regulation of P-glycoprotein with the hope of treating CNS diseases.

MedicalResearch.com: What are the main findings?

Response: Our most recent finding shows that the antidepressant, amitriptyline, suppresses P-glycoprotein pump activity. The discovery is significant because P-glycoprotein restricts most CNS targeted drugs from entering the brain. If fully translatable to human patients, suppression of P-glycoprotein could allow higher levels of CNS therapeutic drugs to reach their intended target.

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Vagotomy May Point To Gut Origin of Parkinson’s Disease

MedicalResearch.com Interview with:

Karin Wirdefeldt, MD, PhD</strong> Associate professor Karolinska Institutet Stockholm, Sweden

Dr. Wirdefeldt

Karin Wirdefeldt, MD, PhD
Associate professor
Karolinska Institutet
Stockholm, Sweden

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

Response: It has been hypothesized that Parkinson’s disease may start in the gut and spread to the brain via the vagal nerve. We found that people who had a truncal vagotomy (ie, the nerve trunk fully resected) at least 5 years earlier were less likely to develop Parkinson’s disease compared to people without vagotomy or people who had a selective vagotomy (ie, only branches of the nerve resected).

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Considering Circadian Rhythms May Aide in Diagnosis of Consciousness Disorders

MedicalResearch.com Interview with:

Copyright Anna-Lisa Bexten Dr. Christine Blume PhD Post-Doctoral Researcher University of Salzburg Centre for Cognitive Neuroscience (CCNS) Laboratory for Sleep, Cognition & Consciousness Research Salzburg

Dr. Christine Blume

Dr. Christine Blume PhD
Post-Doctoral Researcher
University of Salzburg
Centre for Cognitive Neuroscience (CCNS)
Laboratory for Sleep, Cognition & Consciousness Research
Salzburg

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

Response: We are governed by rhythmic processes. Many of these processes follow a circadian pattern, that is, they have a period length of approximately 24 hours and are under tight control of a biological master clock located in the suprachiasmatic nucleus of the hypothalamus. Given the circadian variation in global states like alertness, it is not surprising that consciousness also varies rhythmically in healthy individuals, it follows the sleep-wake cycle.

From a clinical perspective, misalignment of circadian rhythms, which occurs when the sleep-wake schedule is at odds with the light-dark cycle as in the case of night shifts, can cause considerable stress, have detrimental effects on the immune system and impair cognitive abilities. Despite the knowledge that entrained circadian rhythms are important for healthy body and brain functioning, very little is known about circadian rhythms in patients diagnosed with a disorder of consciousness (DOC) following severe brain injuries. We argue that studying circadian rhythms in DOC patients may be especially interesting and important for two reasons.

First, the presence or absence of circadian rhythms as well as anomalies in them could be informative about the state of the patient as well as their potential for recovery.

Second, this could provide information about time points that best capture remaining cognitive functions thereby minimising the risk of misdiagnoses.

Beyond this, examining circadian processes may also provide targets for therapeutic interventions such as light stimulation, which has proven successful in individuals with e.g. circadian sleep disorders. Interestingly, analyses with Lomb-Scargle periodograms revealed significant circadian rhythmicity in all patients (range 23.5-26.3h).

We found that especially scores on the arousal subscale of the Coma Recovery Scale-Revised (CRS-R) were closely linked to the integrity of circadian variations in body temperature.

Finally, we piloted whether bright light stimulation could boost circadian rhythmicity and found positive evidence in two out of eight patients.

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