Yearly Archives: 2015

Adult neurons are touchy things. Too much protein can throw them off course, resulting in neurodegeneration.

After showing how mutant ATAXIN1 (the protein associated with the neurodegenerative disorder spinocerebellar ataxia 1) cannot fold and be discarded properly, resulting in malfunctioning neurons, researchers at Baylor College of Medicine have found an RNA-binding protein called PUMILIO1 that regulates ATAXIN1 levels.

Loss of PUMILIO1 activity – as when it is knocked out or lost –increases the amount of normal ATAXIN1 in the cell and, in studies of mice, causes neurodegeneration that mimics that of spinocerebellar ataxia 1.

Now, in a report that appears in the journal Cell, researchers demonstrate that an RNA-binding protein called PUMILIO1 also regulates levels of the ATAXIN1 protein. When a mouse lacks one copy of the PUMILIO1 gene, the amount of ATAXIN1 increases, starting early in development. The mouse that loses the copy or copies of PUMILIO1 develops symptoms reminiscent of spinocerebellar ataxia 1, loss of motor coordination and degeneration of Purkinje neurons in the cerebellum. Eliminating the copy of the PUMILIO1 gene in mice that already lack a copy of ATAXIN1 reduces the abnormal symptoms and rescues the animals from the disease.

The findings with PUMILIO1 demonstrate that neurons require just the right amount of the important protein – not too much and not too little.

“It shows that cells in the brain are not tolerant of too much of a normal protein,” said corresponding author Huda Zoghbi. “If we can come back and slightly decrease those proteins early in life before the system falters, we may have an effect.. For the late onset spinocerebellar ataxia 1, if we could come up with a strategy to find molecules to decrease the mutant ATAXIN1 – no more than 10 to 20 percent – we might be able to relieve the disease,” said Zoghbi.

“This could be important in the study of other neurodegenerative diseases. We don’t know what proteins are involved and what happens in diseases such as Parkinson’s, Alzheimer, amyotrophic lateral sclerosis and similar disorders,” said lead author Vincenzo Gennarino. “For these and other neurodegenerative conditions that do not fit Mendelian categories, it may prove most fruitful to find factors that elevate the levels of the key disease-driving proteins.”

Source:  Baylor College of Medicine

The current policy approach to tackling dementia is socially and economically unsustainable, according to a new OECD report.

Countries need to take action now to improve the lives of people living with dementia and their carers, prioritise public research on dementia, and improve the incentives for private investment in dementia innovation.

Addressing Dementia: The OECD Response says that the human and financial costs of this incurable disease are huge. Nearly 50 million people are living with dementia worldwide, costing societies over half a trillion US dollars each year, roughly equal to the GDP of Switzerland.

Source:  OECD

Genetic risk for Parkinson’s disease (PD) may be due as much to multiple genes with small individual effects as to single high-risk genes, research suggests.

Nigel Williams (Cardiff University School of Medicine, UK) and colleagues used data from five PD genome-wide association studies, involving 5333 PD cases and 12,298 controls. The team tested 259,577 single nucleotide polymorphism (SNPs) in a subset of 1705 PD cases and 6200 controls from the UK, identifying between nine and 30,157 SNPs that were significantly enriched among the PD patients, depending on the significance threshold of association used.

Applying a polygenic score based on these SNPs to two subsets of patients from the USA and one from Germany revealed significant enrichment of the SNPs identified in the UK patients in these independent cohorts.

Patients lacking single high-risk genetic mutations who nevertheless develop the condition at a young age would be expected to have an increased polygenic risk, say the researchers. “Our study has identified compelling evidence that supports this hypothesis”, they write in the Annals of Neurology.

The authors caution that “the derived polygenic scores have little value for predicting an individual’s risk of developing PD”, but add that “measures of polygenic burden could prove useful in distinguishing PD patients whose disease liability is most likely to carry the largest or smallest genetic component.”

This would therefore facilitate efforts to identify environmental risk factors and gene–environment interactions.

Source;  NewsMedical.net

Researchers have the first conclusive proof that changes to lifestyle among the over-60s can slow mental decline – raising the prospects of dementia prevention programmes that cut your risk of the disease.

Findings from a two-year study of more than 1,200 60 to 77-year-olds in Finland, published in The Lancet medical journal, reveal that a group who received thorough advice about diet, regular exercise sessions, brain training and health check-ups performed better in cognitive tests than a group who received only the standard medical advice.

The results are significant, as it is believed to be the first randomised and controlled trial to conclusively demonstrate that keeping the body healthy in later life also benefits the brain. The participants will now be followed up over seven years to see if those who received the intensive healthcare intervention are less likely to develop dementia.

Overall scores in mental tests after two years were 25 per cent better in the group who received the intensive health programme. In particular areas they were even more striking. Scores for executive functioning – the brain’s ability to organise thought processes – were 83 per cent higher in the intervention group, while mental processing speeds were 150 per cent higher. All participants in the trial were judged to have a high risk of dementia at the start.

The study’s lead investigator is Miia Kivipelto of the Karolinska Instituet, Sweden, who is also the coordinator of the JPND-supported MIND-AD project which is developing multinational strategies for multi-modal preventive trials for Alzheimer’s Disease.

Source:  The Independent

Apple recently announced ResearchKit, a new software framework that turns the iPhone into a powerful tool for medical research.

In conjunction with the announcement of ResearchKit, The Michael J. Fox Foundation is announcing the launch of Fox Insight, a Web-based virtual clinical study open to individuals of any age, both with and without Parkinson’s, worldwide.

The Foundation also collaborated with biotech Sage Bionetworks on the development of a new Parkinson’s mobile app called Parkinson mPower that captures data on Parkinson’s symptoms and progression as part of a clinical study. Parkinson mPower is available for download in the iTunes App Store, and the mPower study is open to all U.S. residents over age 18, with or without a diagnosis of Parkinson’s disease.

Later this year, data collected from participants who enroll in both mPower and Fox Insight will be used to validate the power of these two approaches in accelerating Parkinson’s disease research.

Watch a video by Apple to learn more about how ResearchKit and studies like mPower can help speed scientific progress toward cures by amplifying the patient voice in shaping research.

Read the press release to learn more about mPower and Fox Insight and future plans for both technologies.

Source:  Michael J Fox Foundation for Parkinson’s Research

Some of Europe’s brightest young leaders in research into dementia gathered in London on 27th February 2015 as part of a series of workshops to discuss innovative ideas to address the disease.

More than 50 young experts in fields such as neurology, psychiatry, cellular biology and sociology gathered for a series of discussions and workshops looking at how to help people with dementia live independently for longer and what needs to be done to find a cure. The experts were from 19 countries including the UK, The Netherlands, France, Sweden, Poland, Germany, Croatia, Slovenia and Belgium. Click here for a list of the Young Leaders who attended the workshop.

The workshop was hosted at the Foreign and Commonwealth Office by the UK Government’s Science and Innovation Network in partnership with the World Dementia Council and the Global Action Against Dementia programme, which were established after the UK Government hosted the 2013 G8 Summit on Dementia.

The young leaders were joined by members of the World Dementia Council, which was set up to provide global leadership on tackling the key dementia challenges. The event was also supported by the EU Joint Programming Initiative on Neurodegenerative Diseases (JPND) and Alzheimer Europe.

Flickr slideshow below courtesy of UK Foreign & Commonwealth Office, under Creative Commons licence.

This was the fourth in a series of workshops for young leaders organised by the Science and Innovation Network to support global efforts to achieve the 2013 G8 Summit Declaration commitments.  Previous Young Leaders workshops have taken place in the USA, Canada and Japan with the aim to create a global network of future young leaders which will continue to address the challenges presented by dementia.

The recommendations and outcomes of these workshops will be presented at the World Health Organisation’s First Ministerial conference on Dementia on March 16-17 in Geneva, Switzerland.  At the same time, the global Young Leaders Network will sign up to supporting future activities of the Global Action Against Dementia and the World Dementia Council.

 

Robin Grimes, FCO Chief Scientific Adviser said:
“International science and innovation collaboration is critical to deliver the commitment made at G8 to identify a cure or a disease-modifying therapy for dementia by 2025. This and other young leaders events will make a major contribution by bringing together the best young minds across a range of scientific backgrounds to encourage new ideas and foster new opportunities for innovation.”

 

Philippe Amouyel of the EU Joint Programme on Neurodegnerative Diseases said:
“The scale of the dementia challenge demands a global response, beyond G7 countries. This latest young leader workshop is importing new perspectives and innovative ideas from all over Europe and beyond to tackle the dementia challenge. By harnessing the collective brains of these ambassadors of research we ensure the future of dementia research remains bright, efficient and globalised”.

 

Working in association with the meeting organisers and Alzheimer Europe, JPND member countries actively identified and partly-supported the participation of Young Leaders in the workshop. Indeed, several JPND members increased their allocated support to facilitate the participation of as many identified young leaders as possible.  JPND Management Board chair, Professor Philippe Amouyel represented JPND in the workshop. Click here to view Philippe’s JPND presentation on the day.

The event was also covered by JPND on twitter via @P_Amouyel, @JPNDeurope as well as from the @UKinFrance, @matt_houlihan accounts. Keep up to date using the twitter hashtag #YLDementia.

 

 

On February 26th, 2015, Australia joined the ‘JPco-fuND’ call for proposals.

Due to this late arrival, researchers from Australia can participate as external collaborators in proposals submitted to this call under specific conditions.

The specific conditions for researchers in Australia can be found on the “Specific regulations” page of the call.

Should a proposal involving a collaborator from Australia be recommended for funding, these collaborators are eligible for funding from the NHMRC National Institute of Dementia Research (NNIDR).

*Please Note: Under this call the NNIDR will only fund research that focusses primarily on Alzheimer’s disease and other dementias.

The Joint Programming Initiative “A Healthy Diet for A Healthy Life” is launching a new joint transnational call for research proposals on “Nutrition and Cognitive Function”.

The call aims to support small transnational research consortia with innovative and interdisciplinary approaches tackling the interrelationships between nutrition and cognition.

The call is scheduled to be launched on March-30, 2015 with the deadline for proposal submission scheduled for June 8th, 2015.

The pre-call announcement is available here and through the link below:

 

The March 2015 editorial of The Lancet Neurology is entitled « Teaming up to fight neurodegenerative diseases« .

The editorial focuses on the recently-launched JPcofuND initiative.

To view the editorial, click here or on the link below.

The latest media articles on JPND (including previous Lancet Neurology editorials) are available here.

 

 

Image courtesy of The Lancet Neurology.

A study published in the journal Human Mutation revealed new genetic mutations in a domain of a dynein gene. The study, entitled “Novel mutations in the DYNC1H1 tail domain refine the genetic and clinical spectrum of dyneinopathies,” unlocks new insights into motor neuron diseases such as Spinal Muscular Atrophy.

Dynein is a microtubule motor protein that uses the energy contained in ATP (adenosine triphosphate) molecules to move. Dyneins can be either axonemal, facilitating the movement of cilia and flagella, or cytoplasmic, transporting several intracellular cargos along microtubule tracks. The movement of cytoplasmic dyneins is usually directed towards the center of the cell.

Several studies show evidence that genetic mutations in dyneins underlie some neurodegenerative disorders such as Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and motor neuron diseases.

Source:  SMA News Today