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Noi abordări pentru înțelegerea și tratarea acidemiei propionice
PI: Grant Mitchell, CHU Sainte-Justine, Montreal, Canada
With the PA Foundation grant, we will explore ways to test new treatments in animal and cell models of PA.
PA is caused by deficiency of PCC. The first thing that happens in PCC deficiency is a buildup of propionyl-CoA. Many changes occur in body chemistry in PA, but this all starts with and spreads out from propionyl-CoA. Propionyl-CoA is a key to understanding PA. Totuși, it is seldom measured. This is because measurement requires samples from the tissues that develop complications, and this is not possible in patients. Leading up to this grant, working with mice and cells, we set up the measurement of propionyl and other related CoAs. We looked directly in tissues of PA mice and found that propionyl-CoA was very high, especially during stress and illness.
We determined the survival curve of PA mice under standardized conditions. Also, we found a type of cell that maintains high levels of CoA, similar to those in living tissues. The PA Foundation grant will allow us to combine all of these findings in order to test whether a commonly used drug affects survival and propionyl-CoA levels in PA mice. Also, it will permit us to create a PA cell line for measuring acyl-CoA levels under normal and stressed conditions. Both of these projects will bring us closer to understanding how complications develop in PA and to the goal of rapidly testing new treatment possibilities in animal and cell models of PA, without inconvenience or risk to patients.