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Podocyte Adaptation Proliferation and Ageing

Periodic Reporting for period 4 - PAPAstudy (Podocyte Adaptation Proliferation and Ageing)

Période du rapport: 2020-09-01 au 2021-02-28

The PAPAstudy project aims at discovering new treatment for rare disorders involving the PIK3CA/AKT/mTOR pathway. Our goal is to offer to patients molecular targeted therapy. To this aim we are using complementary in vivo and in vitro approaches, innovative new technology of bioengineering and we develop genetically modified mouse models. We are located in the close vicinity of the clinical department allowing bed to beachside or vice et versa approaches.

This project has broken all the boundaries that were existing between different medical specialities and allowed the
rapid repurposing of a new drug undergoing development in oncology. This project is clearly considered by outside experts as a breakthrough discovery.
Since the beginning of the project, we did develop a new way to isolate primary podocytes (our cells of interest) from mice and to grow them up in vitro. The podocyte is a highly specialized cell with foot processes expansion that function as vasculature-supporting cells, producing basement membrane components and a number of vascular growth factors. These cells play an essential role in renal physiology but their unique localization, as the primary filter, exposes them to many stresses in pathological conditions. In fact these cells are the direct target of many diseases such as diabetes or HIV. We are currently testing and developing various mouse models.

The project resulted in a patent application that has been filled in by the Université de Paris.
Using this method, we discovered promising treatment for other disorders such as mitochondrial diseases, antiphospholipid vasculopathy, CLOVES syndrome or other PIK3CA related overgrowth syndrome.
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