Alzheimer's disease: an offensive on all fronts
According to WHO, by 2025, approximately 34 million people worldwide will be living with a diagnosis of Alzheimer's disease, while it is expected that the greatest increase in the incidence will be observed in developing countries.
At the same time, despite all the efforts of scientists, effective prevention of the progression of this disease still remains an unattainable task.
September 2012 received the status of the first world Alzheimer's Disease Month, an international campaign aimed at raising awareness and destroying prejudice.
In this regard, Professor Philippe Amouyel, director of the DISTALZ program (DISruptive Thinking for Alzheimer's disease) answers questions from the correspondent of the Indian Express Pharma website Shalini Gupta.
DISTALZ is an Alzheimer's disease research laboratory based in Lille, France. Has a certificate issued by the French government "Excellent Laboratory" (Laboratory of Excellence).
And "disruptive thinking" is not "destructive thinking", but a method of solving problems not linearly, step by step, but simultaneously in all directions.
What is the goal of DISTALZ?
The aim of the work set by DISTALZ is to study new mechanisms involved in the pathophysiological processes that cause Alzheimer's disease. A number of such mechanisms are indicated by the results of applying large-scale approaches to the study of the genome. The biological features identified as a result of this will be considered as potential biomarkers or targets for drugs. With the help of a multidimensional approach, DISTALZ plans to form a clinical, social and ethical basis for planning new clinical trials, in which the effectiveness of new promising drugs will be tested on patients at high risk or identified long before the manifestation of Alzheimer's disease using a complex complex of biomarkers.
What is DISTALZ's action plan?
The action plan will be developed in accordance with four main research areas:
From gene to pathophysiological hypothesis: we will strive to characterize the genetic component of Alzheimer's disease by deciphering hitherto unknown aspects of heredity, compiling accurate genetic maps of the disease to identify functional variants of the corresponding genes and stimulating work in other research areas due to the emergence of new putative pathophysiological hypotheses.
From pathophysiological hypotheses to biological mechanisms: the role of these genes and mechanisms will be studied on experimental models of beta-amyloid and tau protein metabolism. Particular attention will be paid to the mechanisms governing the activity of enzymes modulating the production/excretion of alpha-beta-amyloid, the role of recently identified fragments of beta-amyloid precursor protein and tau protein, as well as aggregation and increase in protein deposits. This will allow us to develop more adequate models for screening biological drugs.
From biological mechanisms to effective targets: after that, genetic and biological tests developed based on the results of work in the first two directions will be studied. As part of the epidemiological and clinical activities of our partners, the necessary validation of new biomarkers will be carried out. This will take into account complex interactions with other neurodegenerative and cerebrovascular pathologies, and the ultimate goal of the work will be the personalization of the medical approach.
From effective targets to clinical trials: new data will be introduced into clinical practice by providing access to clearly characterized patients with early stages of the disease and ensuring psychological and social results of early diagnosis, taking into account all ethical aspects of the issue.
Which of the earlier approaches to the development of effective therapy for Alzheimer's disease failed and for what reason?
The understanding of the pathophysiological mechanisms of Alzheimer's disease has significantly deepened over the past 15 years, which has opened up new perspectives, including in the development of new pharmacological targets and cellular/animal models. However, to date, most of the therapeutic approaches that affect these mechanisms do not slow down degenerative processes. One of the possible explanations may be related to the duration of the process of brain damage and delayed initiation of treatment at stages characterized by irreversible dementia and lack of hope for stable brain functioning. Determining the optimal time period for the start of interventions in this case remains an extremely important task. In parallel, other solutions to the problem were also proposed, aimed at preventing or slowing down neurodegeneration by modifying risk factors, for example, through physical exercise or eliminating the risk of vascular diseases. However, these approaches have not been clinically validated to date.
Is Alzheimer's disease genetically determined or hereditary? What do the data obtained by the DISTALZ researchers say?
Like any complex chronic disease, Alzheimer's disease is the result of an interaction between environmental risk factors and genetic predisposition. Several rare cases have been characterized from a hereditary point of view as associated with the presence of a specific mutation in a particular gene. Such cases are often characterized by an earlier onset – at the age of under 65 years (sometimes even under 45 years). However, according to our estimates, for the vast majority of patients, about 60% of cases are associated with a genetic predisposition explained by a multitude of genes with weak effects. The study of the features of these genetic risk factors is necessary to identify new causal mechanisms. Thanks to the results of high-performance genome-wide sequencing, as well as access to large high-quality databases on patients with Alzheimer's disease and people acting as control groups, DISTALZ and partners are working on a systematic characterization of the molecular foundations of the genetic components of the disease. Over the past three years, using the results of Genome Wide Association Studies (Genome Wide Association Studies) we were able to localize genes containing single nucleotide polymorphisms, or "snips" (from the English single nucleotide polymorphisms, SNP) associated with the risk of developing Alzheimer's disease. Thanks to the EADI consortium (European Initiative for the Study of Alzheimer's Disease), which includes 5 countries, 6,322 cases of the disease and 10,373 controls, 10 new genes have been identified. The identification of several of these genes was the result of collaboration with other consortia, including ADGC (Genetic Consortium for the Study of Alzheimer's Disease), GERAD (Genetic and Environmental Exposure Risk in Alzheimer's Disease), CHARGE (Cohorts for Genomic Epidemiology of Heart Disease and Aging) and IGAP (International Genomic Project on the study of Alzheimer's disease).
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Express Pharma:
A multidisciplinary approach to Alzheimer's.
27.09.2012