Gene Therapy Shows Promise for Hemophilia

February 21, 2018 | by Katie Neith

Chatterjee-saswatee Saswati Chatterjee, Ph.D.
For some people with hemophilia A, a disease characterized by the body’s inability to form blood clots due to lack of enough clotting factor VIII, even a small cut can cause incessant bleeding. Major trauma or surgery pose much greater risks.

This relatively common condition, which is seen in approximately one in 5,000 births, is an inherited genetic condition and currently has no remedy. But Saswati Chatterjee, Ph.D., a professor in the Department of Surgery and member of Beckman Research Institute of City of Hope, thinks she may know a way to cure it.

"The potential to cure hemophilia A by correcting the genetic mutations that cause it is a highly attractive therapeutic strategy,” said Chatterjee of her approach.

The California Institute for Regenerative Medicine (CIRM) recently agreed that her research shows promise, granting Chatterjee a Quest Award for over $2 million to fund a project called “Genome Editing of Sinusoidal Endothelial Stem Cells for Permanent Correction of Hemophilia A.” The Quest Awards program “promotes the discovery of promising new stem cell-based technologies that could be translated to enable broad use and, ultimately, improve patient care.”

The work will employ a single-platform technology developed by Chatterjee and her City of Hope lab members that enables either gene editing or gene therapy with a built-in in vivo delivery system. The foundational technology is a novel non-nuclease-based gene editing platform that is being developed to help find cures for rare genetic diseases.

In May 2016, City of Hope announced that it had licensed this pioneering adeno-associated virus (AAV)-based gene editing technology exclusively to Homology Medicines Inc., a newly-formed genetic medicines company. As part of this exclusive relationship, Homology continues to sponsor Chatterjee's research and development of the technology at City of Hope, including her work on hemophilia A.

Chatterjee, who is both the scientific co-founder of Homology Medicines and chair of the company’s Scientific Advisory Board, plans to use the technology to develop a permanent therapeutic approach for hemophilia A by editing the clotting factor VIII (FVIII) gene in the liver — the primary site of FVIII production — using a stem cell-derived, highly efficient genome editing vector, or AAV. AAVs are nonpathogenic viruses that are naturally present in the majority of healthy individuals and possess unique gene editing and gene transfer properties, including unmatched precision, efficiency and on-target in vivo editing of genetic mutations. Chatterjee and her lab were the first to isolate and study this novel family of AAVs derived from human hematopoietic stem cells.

“Importantly, this approach could develop a permanent cure for hemophilia A, but will also serve as a model for correction of multiple liver-based genetic diseases via genome editing of liver stem cells,” said Chatterjee, who points out that the current annual cost of treating hemophilia A is staggering both economically and from a quality of life standpoint.

With the CIRM grant, Chatterjee will work toward her goal by identifying the best AAV-based genome editing vector for correcting the FVIII gene in individual cells and testing therapeutic methods in animal models with the hope of moving the work into clinical trials.

“The funding provided by CIRM will enable to us develop and test this genome approach to potentially cure hemophilia A and eventually help bring it to the clinic,” said Chatterjee. “If successful, this project will develop a cure for a devastating, incurable inherited disease that carries a huge quality of life and economic cost. It will likely serve as a model for developing cures for other inherited diseases.”




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