Welcome to a presentation on Acid β-Glucosidase or Glucocerebrosidase.
Throughout this talk, we'll refer to this as GCase.
My name is Gregory A. Grabowski.
I'm a Physician, Professor Emeritus in
the Department of Pediatrics and in the Division of
Human Genetics at Cincinnati Children's Hospital Medical Center,
and I am Chief Scientific Officer at Kiniksa Pharmaceuticals,
Ltd in Wellesley, Massachusetts.
We will first deal with the importance of GCase and its role in disease.
GCase degrades glucosylceramide, which is
an important glycosphingolipid in development and within all cell membranes,
the precursor to ceramide and is
a critical signaling lipid in the regulation of apoptosis and inflammation.
Defective GCase causes a disease called Gaucher disease.
This is a common lysosomal storage diseases and GCase is a lysosomal hydrolase.
It has been a prototype for molecular therapies.
GCase has become a target for molecular therapies and, in particular,
the development of enzyme therapy by supplying wild type functional GCase by
intravenous administration has improved the lives of
patients with Gaucher disease over the past 15 years.
Gene therapy has also been used in exploratory ways for
the expression of the GCase gene in selected cell types,
in particular, in stem cells of
the hematopoietic origin since the disease relates to the macrophage system.
In addition, expression at high levels in other organs such as the liver could be
used as an organoid approach to the therapy of Gaucher disease.
Finally, it has become a target for the development of a new method of
treatment with significant potential termed chaperone therapy in
which the endogenous defective GCase activity is
enhanced by use of small molecules to re-conform the defective enzyme.