Stroke: 3rd cause of mortality, 1st cause of handicap in adults, and 2nd cause of dementia after Alzheimer disease. 1 500 000 strokes occur each year. Today only a single drug, the tPA, is available to treat stroke patients at the acute phase of the disease. However this treatment requires a CT scan or an MRI before treatment to eliminate a cerebral hemorrhage, and therefore can be used to treat only 5% of patients. Moreover, tPA has a short therapeutic window of 3 to 4.5hrs. For all these reasons, there is a need to develop neuroprotective compounds: 1) targeting different cell types, 2) including multiple pathways involved in cell death, and 3) extensively studied in different animal species and experimental models. NEUROKIN develops neuroprotective agents for the treatment of acute neurological diseases. Its data have shown that inhibition of CDKs has a neuroprotective effect in vitro and in rodent stroke models. The most advanced compound, NK-102, has already undergone some preclinical development, no acute toxicity was observed, and it is able to cross the blood brain barrier. INSERM U919 has a large expertise on rodent and primate stroke models. It has an imaging platform that is unique in France (MRI, PET scan). INSERM U615 is specialized in molecular genetics and epidemiology. It has a large expertise in genomic studies in human. The main objectives of this project are 1) to perform extensive pharmacological studies well controlled in rodents using several experimental models of stroke (STAIR guidelines), 2) to validate NK-102 action mechanisms after stroke in the brain of nonhuman primates, and 3) to initiate regulatory preclinical studies on NK-102, in order to increase probability of success in the clinic.

Prostate cancer is by far the most common cancer for men. A vast variety of prostate cancer treatments are today performed in clinical routine. However, most of them act on the entire gland and are characterized by a high rate of side effects that considerably impact the quality of life of the patient. From an economic point of view, the high side-effect rates of these therapies lead to particularly expensive aftercare costs. The search for improved solutions for the treatment of prostate cancer remains a major societal challenge. This issue is emphasized by the fact that constant improvement of prostate cancer diagnostic tools allows detecting highly localized and small tumors at an early age. In such cases, whole-gland treatment approaches are highly controversial. The high risk of side effects often justifies the choice of an active monitoring of the patient rather than therapy. In recent years, a very attractive therapeutic alternative treatment is gaining in popularity among experts: focal therapy. This is a localized treatment, restricted to cancerous zones, with the objective of preserving healthy functional tissues inside and outside of the organ, and thus the quality of life of the patient. Finally, focal therapy has a high potential to reduce the intervention cost and duration, and the cost of aftercare. However, the current brachytherapy procedures are not fully exploiting the latest state of the art in dosimetry calculation, guidance and imaging capabilities, and thus do not yet meet the requirements for a robust focal treatment. The ambition of the FOCUS project is to provide an innovative focal brachytherapy system, less invasive, with fewer side effects, in rupture with current brachytherapy procedures, capable of accurately irradiating very localized areas, while significantly decreasing the time of the intervention. To achieve such innovative focal brachytherapy system, a new hardware platform dedicated to transperineal prostate punctures will be developed as a part of the project including the use of new 3D Lateral endocavitary ultrasound probe. An essential innovation will be the intraoperative ultrasound-based target guidance in order to control with accuracy the instrument placement during the intervention. This will include multimodal image-fusion algorithms and real time navigation methods. A specific challenge is also the accuracy of the dosimetry. This calculation, already critical in global brachytherapy, is even more important when it comes to targeting small areas. We propose to develop the first clinical treatment planning system integrating edema prostate model and a fast and personalized Monte Carlo dosimetry calculation on GPU. New automatic seed detection in ultrasound images will be used to calculate the real in vivo dosimetry at any moment of the procedure and would thus enable intra-interventional correction in case of deviation from the planned dose distribution. Finally, all developed hardware and software will be integrated into a unique system. This demonstrator and the new clinical protocol of the novel focal brachytherapy procedure will be assessing using realistic phantoms in a clinical context. The FOCUS project is ambitious since it aims at transferring its research developments to health care industry through the industrial partner. The proposed system appears as a solution for a quarter of a million men diagnosed with prostate cancer each year worldwide, for whose no treatment is applied because the risk-benefit is deemed unsatisfactory. Brachytherapy stands out as an approach with a particularly high potential in the focal therapy market. Some systems and methods that will be developed in this project may also be used for other focal therapy approaches, which leverage the economic potential of the project and reducing the investment risk. Finally, patents and scientific publications will be generated by the FOCUS project.