Validation of MT5-MMP as a new target in Alzheimer’s disease using innovative chemical and biological therapeutic strategies – MT5-AD

Despite the many therapies being studied for Alzheimer's disease (AD), a cure does not yet seem to be within reach. A more holistic approach of the disease and its treatment that takes into account its multifactorial etiology, should help us to establish new conceptual paradigms and more efficient therapies. To this end, it is important to discover new targets whose modulation prevents amyloidosis and/or other pathogenic hallmarks (e.g. neuroinflammation). We have found that proteinases of the MT-MMPs family would be among these new targets, at the crossroads of various pathogenic events. MT5-AD seeks to validate the therapeutic value of one of these proteinases in the preclinical context of AD, by applying state-of-the-art chemical, biophysical and biological engineering in a combination of human and mouse models that includes iPS-derived human neural cells from AD patients and transgenic mouse models of AD. The MT5-AD consortium is composed of 4 leading laboratories in the fields of Alzheimer's disease, chemical medicine, structural biology and brain drug delivery, which have been collaborating for several years. Based on this multidisciplinary complementarity, we hope to generate data paving the way for innovative and clinically relevant therapeutic strategies in AD and beyond.