Important legal notice
 
Contact | Search  
More information on René Descartes

 
  Descartes prizes

Aims and Objectives of the Descartes Prizes

The Descartes Prizes are among the activities supported under the European Commission's Seventh Framework Programme, within the Research Directorate Science and Society.

Science Communication Prize

  • Alzheimer's disease: genetic discoveries pave the way for cure

  • Alzheimer's disease, a yet to be cured form of dementia, causes great distress to sufferers and their families, while also placing a heavy burden on social support systems. In the Eurosecretase project, a joint Belgian/German collaboration undertook ground breaking work into the causes of this debilitating condition - identifying new leads for the treatment and prevention of Alzheimer's.

    Alzheimer's disease affects more than 10% of people over the age of 65 - in Europe, this amounts to some 4-5 million citizens. This complex disease causes gradual destruction of brain cells. Common symptoms include memory loss, problems with reasoning or judgment, disorientation, difficulty in learning, loss of language skills, and impaired ability to perform routine tasks. Sufferers also experience personality changes and behavioural problems, including agitation, anxiety, delusions and hallucinations. There is no cure, and current treatments serve only to slow the rate of deterioration. Although Alzheimer's is extremely debilitating, victims frequently survive for a number of years. This creates grave problems for carers, and puts considerable financial strain on national healthcare systems.

    The Eurosecretase project has made important progress in confirming the causal mechanism of the disease, bringing real hope for the development of an effective cure. Both, the rare inherited form of Alzheimer's and the more common sporadic form result from lesions in the brain following the build-up of deposits known as 'amyloid plaque'. The plaque comprises amyloid peptide fragments (Aß) derived from mutations in amyloid precursor protein (APPß) and in genes known as presenilin 1 (PS1) and presenilin 2 (PS2). It was believed that substances called secretases, which act as 'chemical scissors', are responsible for cleaving Aß fragments from the longer molecular chains. But, prior to the present project, there was no absolute proof of this fact, nor of the exact nature of the secretases.

    The researchers were able to show that the presenilins play crucial roles in the generation of neurotoxic Aß, which proved to be a fundamental breakthrough in understanding the whole phenomenon. In addition, they developed a novel in vivo/in vitro experimental system, where cultured living brain cells could be analysed to confirm that the absence of secretases blocked the 'scissor' reaction. The partners eventually succeeded in demonstrating that the absence of PS1 did not inhibit the cleavage of APPß by all types of secretase, but was instrumental in achieving a five-fold drop in the production of Aß. In fact, they determined that PS1 is, itself, one of the secretases - and, as such, an important potential target for curative drug development.

    The premature deaths of the genetically engineered mouse embryos indicated that presenilins perform other vital functions in cell development and immune response, therefore their complete elimination as means of curing Alzheimer's is not possible. The researchers discovered that partial inhibition of the presenilin function could be sufficient to reduce Aß production to a level at which amyloid plaque formation will no longer occur.

    Many more scientists around the world are now following up the pioneering work of Eurosecretase, further increasing understanding of the part played by secretases in biology. The pharmaceutical industry sees them as prime drug development targets, and is using the techniques coming out of the project as tools to optimise the eventual balance between efficacy and risk. The researchers are providing consultancy services to numerous companies, while their laboratories are active in assisting with the validation of candidate compounds and setting up high-throughput assays for drug screening. The combination of sophisticated transgenic techniques and advanced cell biological methods enabled the researchers to produce crucial data that have come to be regarded as milestone findings in this highly competitive area.

    Contact:

    Prof. Bart de Strooper of the Catholic University of Leuven (Belgium) and Prof. Paul Saftig of the Christian-Albrechts- Universität of Kiel (Germany).

    Websites: http://www.kuleuven.ac.be/med/ncbgtl/ and http://www.uni-kiel.de/Biochemie/agsaftig/index.html


Descartes Prizes:    2005  2004  2003  2002  2001  2000