Introduction d'Alain Fischer
Knowledge of the mechanisms of genetic diseases is indispensable to the development of new therapeutics. In effect, to know precisely which metabolic pathway is modified enables the definition of a therapeutic target, the obligatory first step in the search for new treatments. Currently, research is following numerous leads. In some cases, methods using techniques of “molecular screening” may identify a chemical or a biological molecule capable of bypassing a defect or restoring a deficient pathway. In other cases and depending on the type of gene mutation, research into new therapeutics may target the messenger RNA (notably, to avoid its degradation or to modify its composition) of the mutation involved. When these approaches are not yet feasible, the replacement of defective or absent cells by the transplantation of normal cells (cell therapy) or the introduction into the defective cells (or their offsprings) of a normal copy of the mutated gene (gene therapy) constitute promising paths of research that will become even more important when it will be possible to use stem cells.
Thus,
Imagine plans to transform knowledge on genetic diseases into effective treatments as rapidly as possible. We foresee that this research will also have an impact on more common diseases by serving as models for the development of their treatment.
Genetic diseases are numerous and complex. They affect all the biological systems of the human body. Research at
Imagine involves different areas in biology: notably, immunology and infectious diseases, stem cells, brain and muscle development, metabolism and nephrology. Understanding each genetic disease involves a long process which begins by the most precise description of the consequences of the disease. The identification of the responsible gene is the first key step. Here begins the scientific adventure including often unpredictable events. When the sequence of the gene is elucidated, studies are undertaken to deduce the structure and function of the protein. The protein must then be described: under what conditions is the protein present, in which cells, where precisely in these cells is the protein expressed? What are its partners? What are the molecular consequences of its partial or total inactivation, or, conversely, its over-expression in the cells or in the model organisms? This long process reconstitutes, little by little, the metabolic pathway of a protein’s action. It can then be deduced how a certain mutation has a certain pathologic consequence. Immunology is one of the priority areas of
Imagine. In immunology, several research groups have developed activities to understand the basic mechanisms of genetic diseases of the immune system and, more generally, to analyze the genetic predisposition of certain infectious diseases as well as the susceptibility to auto-immune diseases. Other collaborative projects in this area are in progress and include the analysis of progenitor cells of the immune system. This work will contribute to the elaboration of new cell and gene therapies of genetics diseases of the immune system. The studies of abnormalities of development of the nervous system and muscle constitute a second priority axis of the Institute.
Several teams already focus their research on diseases of the nervous system:
- Genetic and molecular bases of recessive mental retardation
- Behavioral problems
The study of stem cells and embryo-fetal abnormalities is a third priority area of the Institute. Stem cells are progenitor cells capable of either differentiating into specialized cells or auto-renewing and remaining undifferentiated progenitors. The study of stem cells is of considerable cognitive and therapeutic interest and is an important transversal axis of the Imagine program, in connection with the biotherapy department and the clinical units. Taken together, invaluable knowledge will be acquired, enriching our understanding of human biology and, more specifically, human development.
In summary, the scientific program of the Institute will focus on advancing the understanding of the pathophysiology involved in the following principal scientific areas:
- Immunology and infectious diseases
- Biology of development and its abnormalities in the nervous system, in muscle and in the kidney
- Metabolic diseases
- Differentiation of stem cells
- Embryo- fetal morphogenesis
Two ambitious projects are considered as priorities for Imagine:
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The development of new diagnostic tools especially in the area of pre-implantatory diagnostics (DPI) and prenatal diagnostics (DPN). The objective is to improve the procedures of prenatal genotypic diagnosis to optimize their reliability, to reduce their invasive constraints, to simplify them and to reduce the length of time of diagnosis.
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The acquisition of new therapeutic solutions derived from scientific advances such as cell therapy and gene therapy.
The scientific program of the Institute for Genetic Diseases
Imagine is ambitious. It has been detailed in the convention of objectives signed with the Ministry of Research and renewable for 5 years. It was validated by a site visit of the International Scientific Advisory Board on March 5, 2009. The
Imagine program hopes to enlarge the horizons of medicine: definition of new diagnostic and prognostic markers and, above all, new therapeutics whether based on drug discovery (chemical or biological), cell therapy, gene therapy, surgical prowess or new technology. From such progress, new basic research and clinical questions will inevitably emerge. New cycles of research will be undertaken in the continuous hope to improve patient care and treatment.