The strategy developed by research teams and development of I-Stem aims to identify innovative therapies applicable to rare genetic diseases based on exploring the potential offered by human pluripotent stem cells.
Human pluripotent stem cells from two sources today, one physiological embryonic stem cells “ES” from the embryo, and the other experimental cells “iPS” induced pluripotency by reprogramming genetic somatic cells. These cells have two main properties, unlimited self-renewal that can produce laboratory any desired number of undifferentiated cells and pluripotency, which provides access from the undifferentiated cells in all cell types of the human organism. The mastery of these two cardinal properties is the essential work done by hundreds of research teams around the world since the emergence of human ES cells in 1998. The exploitation of these properties controlled for the treatment of genetic diseases is the goal of I-Stem.
Therapeutic strategies developed by teams of I-Stem are strategies break from all that has been done so far. However they fit into two major areas of therapeutic research explored with other strategies by many other academic and industrial players, the cell therapy and that of drug discovery.
Cell therapy, as envisaged by the teams of I-Stem, is primarily based on the identification of experimental protocols that can specifically guide differentiation of pluripotent cells to a cell fate, which presents a interest for the replacement of the defective cell population from the patient (the striatal neurons for Huntington’s disease, the cells of the retinal pigment epithelium for retinitis pigmentosa, keratinocytes for genodermatoses, etc.). From tens of ES cells, nature normally guide the differentiation into hundreds of different cell fates during embryonic and fetal development through various signals, including proteins (cytokines). At the same time, the cells proliferate to build the body, gradually changing to finally reach those characteristics of mature cells of the body to which they belong. Teams I-Stem use data from basic research on the mechanisms of development to build protocols that copy, at best, natural phenomena and their timing must also be respected. Dozens of protocols already exist, to achieve cell fates very accurate. Once this work is completed, a second stage is committed, in which researchers of I-Stem, in collaboration with specialists in animal models of diseases targeted by the therapeutic explore the effects of experimental transplantation of cells obtained laboratory. The ability of the grafts to grow and integrate into the host tissue is considered, in general, in rodents. The functional efficiency of the graft, its ability to regenerate lost the activities of the body, is the subject of studies in models closer to humans. Finally, once all these studies satisfactorily, the teams I-Stem associate with appropriate clinical research teams to carry out the experimental protocols to transfer patient in the context of research called ” translational “culminating in the clinical trials. The provision of treatment is ultimately the goal.
The strategy of drug discovery may correct defects associated with genetic diseases as it continued to I-Stem is based on the access that pluripotent stem cells provide molecular mechanisms involved in these diseases. Through raising campaigns among individuals with genetic defects that cause disease, embryos discarded during a pre-implantation diagnosis or sick people, teams have virtually I-Stem cells for access to any genetic diseases listed. The first step of the programs is then identifying molecular defects which result from the presence of the mutation (outside achieving clean of the protein encoded by the mutated gene itself). This can come in many different aspects, misfolded proteins located in the cell, expressed too much or too little cell functional defects, premature death when put in proliferation, etc.. Once these anomalies characterized, the second step is initiated, during which chemical compounds whose formula can be considered for administration to humans are applied one by one to the cells, looking for corrective action. In order to optimize this research should be tested tens of thousands or hundreds of thousands of different compounds. This requires the intervention of sophisticated robotic technology to produce the required quantities of cells on one hand, to practice drug tests under conditions to identify the compound effective to thousands of thousands of others, on the other hand. Technological research teams of I-Stem dedicated to these developments bioproduction and drug screening broadband. Once identified potentially therapeutic compounds opens a long phase of development requires approaches chemical, biological, toxicological and regulatory variety, for which I-Stem systematically seeks partnerships with industry which is the specialty. Once this development culminated in the product of the successive phases of clinical trials, for a provision of patients.