Monthly Archives: május 2014

A novel experiment to study the Huntingtin protein recently arrived at its orbital laboratory on the International Space Station along with 5,000 lbs of cargo delivered on board SpaceX’s Dragon capsule.

When mutated, the huntingtin protein causes Huntington’s disease, a hereditary illness that impairs muscle control and cognition. There is no cure for the disorder, which is typically diagnosed in mid-adult life.

To understand how proteins function, scientists often use a technique called X-ray crystallography, which allows them to peer at the molecular structure of the protein when it’s in a solid crystal form. So far, researchers haven ot had much luck creating crystals of the huntingtin protein on the ground, but crystals tend to grow more effectively in microgravity.

"On the ISS, we really hope to be able to finally get crystals that are big enough and perfect enough that we can solve the structure of the huntingtin protein," said Gwen Owens, designer of the study.

If the experiment works, the huntingtin crystals will be brought back to Earth this Autumn to be studied in an X-ray crystallography lab.

SpaceX, a private company based in Hawthorne, Calif., launched the Dragon resupply ship toward the International Space Station on Friday (April 18) from Cape Canaveral Air Force Station in Florida using its own Falcon 9 rocket. The mission was SpaceX’s third of 12 cargo delivery missions under a $1.6 billion contract with NASA.

Source: Huffington Post

Professor Philippe Amouyel outlines recent JPND progress in the latest edition of International Innovation magazine.

To access the individual article, click on the link below.

International Innovation Magazine

Click here, or on the link below to access other international press articles related to JPND. 

For more information on International innovation magazine, click here.

A scientific team led by the Gladstone Institutes and UC San Francisco has discovered that a common form of a gene already associated with long life also improves learning and memory, a finding that could have implications for treating age-related diseases like Alzheimer’s.

The researchers found that people who carry a single copy of the KL-VS variant of the KLOTHO gene perform better on a wide variety of cognitive tests. When the researchers modeled the effects in mice, they found it strengthened the connections between neurons that make learning possible – what is known as synaptic plasticity – by increasing the action of a cell receptor critical to forming memories.

The discovery is a major step toward understanding how genes improve cognitive ability and could open a new route to treating diseases like Alzheimer’s. Researchers have long suspected that some people may be protected from the disease because of their greater cognitive capacity, or reserve. Since elevated levels of the klotho protein appear to improve cognition throughout the lifespan, raising klotho levels could build cognitive reserve as a bulwark against the disease.

"As the world’s population ages, cognitive frailty is our biggest biomedical challenge," said Dena Dubal, MD, PhD, assistant professor of neurology, the David A. Coulter Endowed Chair in Aging and Neurodegeneration at UCSF and lead author of the study,published May 8 in Cell Reports. "If we can understand how to enhance brain function, it would have a huge impact on people’s lives."

Klotho was discovered in 1997 and named after the Fate from Greek mythology who spins the thread of life. The investigators found that people who carry a single copy of the KL-VS variant of the KLOTHO gene, roughly 20 percent of the population, have more klotho protein in their blood than non-carriers. Besides increasing the secretion of klotho, the KL-VS variant may also change the action of the protein and is known to lessen age-related cardiovascular disease and promote longevity.

The team’s report is the first to link the KL-VS variant, or allele, to better cognition in humans, and buttresses these findings with genetic, electrophysiological, biochemical and behavioral experiments in mice. The researchers tested the associations between the allele and age-related human cognition in three separate studies involving more than 700 people without dementia between the ages of 52 and 85. Altogether, it took about three years to conduct the work.

"These surprising results pave a promising new avenue of research," said Roderick Corriveau, Ph.D., program director at NIH’s National Institute of Neurological Disorders and Stroke (NINDS). "Although preliminary, they suggest klotho could be used to bump up cognition for people suffering from dementia."

Having the KL-VS allele did not seem to protect people from age-related cognitive decline. But overall the effect was to boost cognition, so that the middle-aged study participants began their decline from a higher point.

Source:  NIH, USA

Conditions which may accelerate the spread of Parkinson’s disease, and a potential means of enhancing naturally-occurring defences against neurodegenerative disorders, have been identified in two new studies.

Both sets of results have emerged from collaborations between the research groups led by Chris Dobson, Tuomas Knowles and Michele Vendruscolo at the University of Cambridge, who focus on understanding protein "misfolding" diseases. These include Alzheimer’s and Parkinson’s diseases, as well as numerous others.

The first study provides evidence that the early spread of the protein aggregates associated with Parkinson’s appears to happen at an accelerated rate in mildly acidic conditions. This suggests that particular compartments within brain cells, which are slightly more acidic than others, may turn out to be appropriate targets for future treatments fighting the disease.

Meanwhile, researchers behind the second study appear to have identified a way in which the effectiveness of so-called molecular "chaperones", responsible for limiting the damage caused by misfolded proteins, can be significantly enhanced.

The papers appear in the latest issue of Proceedings of the National Academy of Sciences.                                   

Source: University of Cambridge                                                                                                                                                                                                                                                                                                                                                             

French research into the impact of a premature menopause (less than 40 years old) on cognitive function in later life indicates that premature surgical menopause and premature ovarian failure are associated with long-term negative effects on cognitive function.

These effects are not offset by menopausal hormone therapy (HT) completely.

The potential long-term effects on cognitive function should be included in the risk / benefit considerations for surgical menopause (ovariectomy) in younger women.

No significant link was discovered between premature menopause and the risk of dementia in later life.

The three Dementia Challenge Champion Groups have written brief reports detailing their progress during the past year.

These reports feature in aletter to the UK Prime Minister which also reiterates achievements since the Prime Minister’s Dementia Challenge was launched 2 years ago and describes the Champion Groups’ ambitions for the third year of the dementia challenge.

To recap, the challenge’s three champion groups comprise:

  1. The Dementia Health and Care Champion Group: co-chaired by: Sir Ian Carruthers (NHS South West) and Sarah Pickup (ADASS).
  2. The Dementia Friendly Communities Champion Group: co-chaired by: Jeremy Hughes (Alzheimer’s Society) and Angela Rippon.
  3. The Research Champion Group: led by the Ministerial Advisory Group on Dementia Research (MAGDR) and co-chaired by Dame Sally C. Davies and Professor Patrick Maxwell.

A glucagon-like peptide-1 agonist (GLP-1 agonist) medication, Exenatide, marketed as Byetta® and Bydureon® is used in the treatment of insulin resistance in patients with Type 2 diabetes.

Several recent discoveries have highlighted common cellular pathways that potentially relate neurodegenerative processes with abnormal mitochondrial function and abnormal glucose metabolism.

A follow-up study of patients with Parkinson’s disease (PD) who participated in an earlier "proof of concept" clinical trial using exenatide showed that improvements persisted twelve months after discontinuing exenatide therapy. These data provide strong encouragement for the further study of this drug in patients with PD, report researchers in theJournal of Parkinson’s Disease.

Earlier studies had shown that exenatide is neuroprotective and promotes functionally beneficial neuroplasticity in animal models of neurodegeneration. Furthermore, exenatide has a favorable safety profile, with only relatively mild gastrointestinal side effects (including nausea and weight loss) as frequent adverse events.

In an earlier "proof of concept" randomized controlled trial published in May 2013, participants were randomized to either self-administer exenatide in addition to their regular PD medications or to act as controls, i.e., receive their conventional PD treatment only. All of the participants had moderate severity PD. In total, 44 patients (20 in the exenatide group and 24 controls) completed the trial. After 12 months the results showed significant and clinically meaningful differences in both motor and cognitive symptoms between those patients receiving exenatide and the controls. At 14 months, when the patients had discontinued exenatide for two months, the exenatide-treated and control groups still differed from each other. The authors concluded that the study supported potential disease-modifying benefits of exenatide in PD, while acknowledging the lack of a placebo arm.

Source: Science Codex

Are patients with Parkinson’s disease „blind to blindsight?” That’s not a trick question, but the focus of an inquiry by neuroscientists from Rush University Medical Center as well as the Centre Hospitalier and University of Luxembourg.

Scientists have developed the concept of "blind to blindsight" to integrate data on visual impairments that contribute to the disability and diminished quality of life in patients with Parkinson’s disease.

Blindsight is observed in people who are blind as a result of a lesion in the visual cortex of their brain. Although these individuals are blind, they maintain the ability to sense accurately a light source or a rapid movement without being aware of it. Strangely, blindsighted patients even can respond appropriately to emotional facial expressions, especially those expressing fear or danger. It is believed that these visual stimuli can be turned directly into actions (e.g., movement of the eyes) by passing through lower areas of the brain. Thus, these retained visual functions operate as unconscious responses to visual stimulation even when there is extensive damage to the visual cortex.

Conversely, patients with Parkinson’s disease, who do not have a problem with their general vision, are unable to do these tasks: they display slowness and reduced accuracy of pursuit eye movements. They often have difficulties grasping a moving object, and show decreased sensitivity to low contrast and impaired ability to read "right away" other people’s facial expressions.

Taken together, these Parkinson’s disease symptoms represent major impairments in blindsight – hence, "blind to blindsight."

The "blind to blindness" concept is described in theJune issue of the journal Brain by Dr. Nico J. Diederich, from Centre Hospitalier and University of Luxembourg, who is a visiting scholar at Rush University. He was joined by the Rush researchers Glenn Stebbins, PhD, and Dr. Christopher G. Goetz, and neuropsychologist Christine Schiltz, PhD, from the University of Luxembourg.

Based on this new concept, the researchers could now propose a new concept how to comprehensively understand within one visual system—blindsight—numerous visual signs and symptoms of patients with Parkinson’s disease. Impairment of the evolutionary old networks in the brain operating within the blindsight visual system form the basis of the visual problems in Parkinson’s disease.

Source: Rush University USA

A recent study conducted by researchers from the Mayo Clinic in Florida examines the discovery of an atypical type of Alzhiemer’s–one that neuroscientists claim is not well recognized nor appropriately treated.

The variant, called hippocampal sparing AD, made up 11 percent of the 1,821 AD-confirmed brains examined by Mayo Clinic researchers — suggesting this subtype is relatively widespread in the general population. The Alzheimer’s Association estimates that 5.2 million Americans are living with AD. And with nearly half of hippocampal sparing AD patients being misdiagnosed, this could mean that well over 600,000 Americans make up this AD variant, researchers say.

In an oral presentation at the annual meeting of the American Academy of Neurology in Philadelphia, scientists say hippocampal sparing AD often produces symptoms that are substantially different from the most commonly known form of AD, which affects the hippocampus, the center of memory.

The patients, mostly male, are afflicted at a much younger age, and their symptoms can be bizarre — behavioral problems such as frequent and sometimes profane angry outbursts, feelings that their limbs do not belong to them and are controlled by an “alien” unidentifiable force, or visual disturbances in the absence of eye problems, researchers say. They also decline at a much faster rate than do patients with the most common form of AD.

“Many of these patients, however, have memories that are near normal, so clinicians often misdiagnose them with a variety of conditions that do not match the underlying neuropathology,” says the study’s lead author, Melissa Murray, Ph.D., an assistant professor of neuroscience at Mayo Clinic in Florida.

Many of these patients are diagnosed with frontotemporal dementia, a disorder characterized by changes in personality and social behavior, or corticobasal syndrome, characterized by movement disorders and cognitive dysfunction. Language dysfunction is also more common in hippocampal sparing AD, although patients do not have vocal or hearing deficits.

“What is tragic is that these patients are commonly misdiagnosed and we have new evidence that suggests drugs now on the market for AD could work best in these hippocampal sparing patients — possibly better than they work in the common form of the disease,” Dr. Murray says.

Source: Canada

A Youtube-hosted webinar will take place from 13:00-13:45 (GMT+1/BST) on Friday, May 9th, 2014, to outline the main aspects of the JPND „Rapid Action” Call for Working Groups on Longitudinal Cohorts.

On April 23rd, 2014, JPND announced the launch of a new type of Call – a Call for working groups – to inform cohorts for neurodegenerative disease research.  

This "rapid action" is part of a series of new JPND initiatives, designed to enhance the impact of research by aligning and building upon existing national programmes and initiatives (click here for a call-related interview with the JPND Management Board chair – Prof. Philippe Amouyel).

The May 9th webinar, delivered by the Medical Research Council, UK, will give a brief introduction to the call, and will answer any questions that interested parties may have, such as Working Group composition and submission of proposals.

If you have questions that you would like answered on the Webinar, these can be emailed in advance of, or during the webinar, to [email protected] with the subject line "WEBINAR QUESTION".

You can view the webinar on May 9th via the JPND website (see direct link below).  If you miss the webinar, a recorded Youtube video will be made available on the same page after the webinar has ended.