Monthly Archives: december 2014

Age-related neurodegenerative disorders including Alzheimer’s disease and Huntington’s disease (HD) consistently show elevated DNA damage, but the relevant molecular pathways in disease pathogenesis remain unclear. One attractive gene is that encoding the ataxia-telangiectasia mutated (ATM) protein, a kinase involved in the DNA damage response, apoptosis, and cellular homeostasis. Loss-of-function mutations in both alleles of ATM cause ataxia-telangiectasia in children, but heterozygous mutation carriers are disease-free. Persistently elevated ATM signaling has been demonstrated in Alzheimer’s disease and in mouse models of other neurodegenerative diseases.

This new study shows that ATM signaling was consistently elevated in cells derived from HD mice and in brain tissue from HD mice and patients. ATM knockdown protected from toxicities induced by mutant Huntingtin (mHTT) fragments in mammalian cells and in transgenic Drosophila models.

By crossing the murine Atm heterozygous null allele onto BACHD mice expressing full-length human mHTT, the researchers show that genetic reduction of Atm gene dosage by one copy ameliorated multiple behavioral deficits and partially improved neuropathology. Small-molecule ATM inhibitors reduced mHTT-induced death of rat striatal neurons and induced pluripotent stem cells derived from HD patients.

The study provides converging genetic and pharmacological evidence that reduction of ATM signaling could ameliorate mHTT toxicity in cellular and animal models of HD, suggesting that ATM may be a useful therapeutic target for HD.

Source; Science Magazine

The JPND Action Group on palliative and end-of-life care has published its report, bringing together for the first time an analysis of gaps and collation of needs and opportunities for neurodegeneration research across JPND countries.

JPND is currently investigating the available evidence and gaps in knowledge in palliative care research in the field of neurodegenerative diseases, with a view to implementing actions within the reach of its global research community.

A JPND Action Group on Palliative and End-of-Life Care met during 2014 and has reported back to JPND. The group was tasked with:

  • Analysing the nature and scale of relevant palliative and end-of-life care research initiatives among JPND member countries and EU-funded initiatives.
  • Consulting with the research community to establish the value of JPND actions.
  • Identifying the gaps within current palliative care research on ND and scoping the requirements to be considered in areas of unmet need.

Implementation of JPND actions in this area will be based on the advice in the report. These actions may include shared working across JPND member countries, funding of competitive calls, coordination of best practices and organization of transnational initiatives designed to share knowledge and provide training that does not currently exist in this research field.

The report can be downloaded at the link below.

As identified in the report, a number of implementation challenges will need to be overcome in order for JPND to support and facilitate research that informs how to shape palliative care across neurodegenerative diseases. The report also identified a number of areas where further thinking is specifically needed to provide the necessary consensus and framework to support future studies of impact for the field. These were:

  • Advance Care Planning which involves carer and family engagement in planning and decision-making over time.
  • The challenges of working with cognitive impairment in terms of communication, symptom management and end of life care.
  • The effectiveness of education + training interventions and linked competencies in practice for a range of generalist and specialist practitioners charged with the care of ND patients.
  • Engaging primary care providers (e.g. GPs, etc.) in palliative care planning.
  • Engaging with national voluntary groups and policy makers on actions and outcomes for ND

Priorities for action will be set by JPND Management Board for announcement in 2015.

A new study entitled “Evaluating the relationship between amyloid-β and α-synuclein phosphorylated at Ser129 in dementia with Lewy bodies and Parkinson’s disease” reports a correlation between α-synuclein and amyloid-β in the brain of patients affected by neurodegenerative diseases, such as Parkinson’s disease. The study was published in the journal Alzheimer’s Research &Therapy.

In this study, the authors measured both soluble and insoluble amyloid-β and α-synuclein in human post-mortem brain tissue and analyzed whether there is a relation between the levels of amyloid-β, total α-synuclein, pSer129 α-synuclein and cognitive function ante-mortem in Parkinson’s disease patients. Their main findings were the discovery of a positive correlation between the levels of insoluble pSer129 α-synuclein with insoluble and soluble amyloid-β protein in most brain regions analyzed. The correlation was significantly higher in Parkinson’s disease and dementia with Lewy bodies patients when compared to controls. Additionally, the authors found that the proportion of α-synuclei phosphorylated at Ser129 correlated with ante-mortem mini-mental state examination.

Their findings establish a pathogenic link between the accumulation of amyloid-β and the phosphorylation of Ser129 at α-synuclein, thus increasing disease severity and the probability of developing dementia. The authors highlight that additional studies are required to understand fully how the interaction is maintained.

Source:  Alzheimer’s News Today

Marisol Touraine, Minister of Social Affairs, Health and Women’s Rights, Geneviève Fioraso, State Secretary for Higher Education and Research, and Laurence Rossignol, Secretary of State for Families, People elderly and Autonomy, recently launched the French National Plan neurodegenerative diseases 2014-2019.

Announced by the President of the Republic, this plan from a wide consultation with stakeholders, has three priorities:

  • Improving the diagnosis and management of patients
  • Ensuring the quality of life of patients and their caregivers
  • Develop and coordinate research

The French Government is committed to a dynamic of progress in research, care and support. The plan takes into account the specificities of each disease and provides concrete solutions to the needs of patients and their caregivers.

In a pilot study, researchers at the Department of Psychiatry and Psychotherapy of the University Medical Center of Johannes Gutenberg University Mainz (JGU) have recently gained new insights into how it may in future be possible to treat patients with the currently most common form of dementia – Alzheimer’s disease.

It seems that a drug that is actually approved for treatment of the dermal disorder psoriasis stimulates the activity of the enzyme ADAM10 in the brain of Alzheimer’s patients. There is already good evidence from basic research that this enzyme should be capable of suppressing Alzheimer’s disease-related effects such as impaired cerebral function and that it thus might improve learning and memory capacity in patients.

The results of the related study have recently been published in the journal Neurology.

Source:  Heathcanal

Eli Lilly and Company and AstraZeneca announced the start of recruitment of patients for the Phase II/III AMARANTH clinical trial of an inhibitor of beta secretes cleaving enzyme (BACE), currently under development as a promising therapy for Alzheimer’s disease.

The AMARANTH Phase II/III clinical trial will evaluate the safety and efficacy of oral AZD3293/LY3314814 against placebo and will assess if this drug can be designated as disease-modifying therapy for patients with early Alzheimer’s disease. The state of early Alzheimer’s disease includes patients with mild cognitive impairment (MCI) associated with Alzheimer’s disease and patients with mild Alzheimer’s dementia. This new study will include more than 1,500 patients in 15 countries, and the treatment will be for 2 years.

Source:  Alzheimer’s News Today

Researchers from the School of Medicine at Washington University in St. Louis (WUSTL) blocked a sleep-regulating protein, orexin, in mice with a form of Alzheimer’s disease, making them sleep longer and blocking brain symptoms of Alzheimer’s disease. The research appeared in the November 24th issue of The Journal of Experimental Medicine.

Also known as hypocretin, orexin is a molecule that controls wakefulness, as well as eating, motivation, and emotion. Orexin is thought to be important for maintaining regular sleep patterns. People with low orexin can have narcolepsy — a condition associated with sleeping excessively. Levels of orexin in the cerebrospinal fluid have recently been found to be decreased in Alzheimer’s disease, and these decreases correspond abnormal sleep patterns.

Source:  Alzheimer’s News Today

 

 

The EU Joint Programme – Neurodegenerative Disease Research (JPND) has announced a EUR 30 million call for neurodegenerative disease research topped-up with EUR 10 million from the Horizon 2020 framework programme for research and innovation of the European Union.

Neurodegenerative diseases such as Alzheimer’s and Parkinson’s are a truly global challenge.  Most of these diseases remain incurable and are strongly linked with aging populations. Dementias alone affect more than 7 million people in Europe and their care is estimated to cost  EUR 130 billion a year. The challenge facing the world of diagnosing, treating and caring for people affected by neurodegenerative diseases is extremely daunting and no single country alone has the expertise or resources necessary to tackle all of the big questions in this area.

JPND was established in 2009 to enable participating EU Member States to work together on the challenge of age-related neurodegenerative diseases, in particular Alzheimer’s. In the past five years, tremendous progress has been made by JPND in terms of increasing coordination, collaboration and alignment between national research programmes and projects related to neurodegenerative diseases.  This has resulted in an unprecedented mobilization of human resources, actions, funding and awareness to tackle this problem which no country can address alone.

JPND have announced a major new cohesive action with the European Commission, entitled ‘JPcofuND’. The initiative expects to launch a joint transnational call for proposals in January 2015 aimed at supporting international research collaborations in three JPND priority areas:  Longitudinal Cohorts, Animal and Cell Models, Risk and Protective Factors. This initiative will see more than EUR 30 million coming from the JPND member countries being made available, with an additional EUR 10 million European Commission “topping up” fund.

According to Professor Philippe Amouyel, Chair of the JPND Management Board

“this unique co-funded initiative further establishes concrete synergies with Horizon 2020 to address this global threat.Thisis a significant scale-up of implementation of the JPND research strategy, and a major step forward towards the realisation of a “European Research Area” dedicated to neurodegenerative disease research – an issue central to the joint programming concept.

European Commissioner for Research, Science and Innovation Carlos Moedas said:

“The EU Joint Programming approach tackles some of the major challenges we face as a society. Thanks to this new co-funded initiative of JPND and the European Commission, top European researchers will be working together to help the millions of people who suffer from Alzheimer’s and other neurodegenerative diseases. By making research more efficient and avoiding the duplication of work, this initiative will increase the prospects of real progress in the prevention and treatment of these diseases, as well as in patient care.”

A pre-call announcement, with the indicative titles of each topic, was made recently on the JPND website.  Further detail will be provided on this page on the call launch date in January 2015.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No. 643417 – JPcofuND

Media enquiries should be directed to:

Derick Mitchell

dmitchell@jpnd.eu

+353 1 442 9015

Wearable devices that are being trialled by Parkinson’s UK to improve symptom management for sufferers have been granted an EU patent, signalling a green light for the devices to enter the European market in the near future.

The Global Kinetics Corporation’s (GCK) KinetiGraph device, worn on the wrist, records patients’ movements and medication to assess dosage levels and their effectiveness. Charity Parkinson’s UK announced in Autumn 2014 that it would trial the wearables on hundreds of patients over the next 12 months.

Source:  Techworld

The first 25 research projects of the Dutch “Delta Plan Dementia” have been announced and will start before the end of the year. The studies vary in focus, from new treatments and prevention to better patient care and support. Results are expected in the coming years.

The 25 studies have received over EUR 21 Million in funding. The Dutch Government was the major contributor. Alzheimer Nederland was the major private investor with a contribution of over EUR 1 Million. Gea Broekema-Prochazka, director of Alzheimer Netherlands said “We expect breakthroughs that are important for the patients that are faced with dementia today and for the patients of the future.”

Source:  Alzheimer Europe