(Dr Joutel) At the AGM in April 2013, Dr Joutel set out
a research project about stem cells. This work has taken place in
collaboration with Dr Sanjay Sinha, of Cambridge, England, who is an expert
in the 10 field of obtaining smooth muscular blood vessel cells from Ips
cells (Induced Pluripotent Stem Cells). The aim is to cultivate smooth
muscular blood vessel cells from the patients who have CADASIL in order to
study the reasons why these vessels are the centre of abnormal deposits of
NOTCH3 and undergo a process of degeneration.
These cells will allow us to understand how the mutated
protein clumps together, and to identify if it is the deposits that are
toxic or the small accumulations of a few molecules of mutated proteins,
etc. The results will be a lot more rapid than when working with mice (that
have to be crossed, allowed to grow old, etc.) Dr Hervé has performed
biopsies on eight patients. With these cells, fibroblasts have been prepared
and cultured in Dr Joutel’s laboratory.
They have been reprogrammed as stem cells in England,
for five patients who have five different types of mutation, and then
redifferentiated into smooth muscular cells. The first results are very
encouraging. It appears that we might see abnormalities such as deposits of
NOTCH3. These cells might constitute another tool with which to test the
antibody anti-NOTCH3 and even allow us to improve it. The Dutch therapeutic
strategy, which aims to modify the mutated protein, is also going to be
tested on these human cells.
(Medical Presentation 2016 Paris France)