Scientists find potential new use for cancer drug

The process of developing gene therapy into a viable treatment has overcome a significant hurdle that allows a stem cell's natural defences to be bypassed.

A new study, led by Associate Professor Bruce Torbett at The Scripps Research Institute (TSRI), found that a drug called rapamycin enables a therapeutic dose of genes to blood stem cells to be administered, while preserving stem cell function.

Rapamycin is commonly used to slow cancer growth and prevent organ rejection, and could lead to the development of more effective and affordable long-term treatments for blood cell disorders where mutations in the DNA cause abnormal cell functions - such as in leukaemia and sickle cell anaemia.

The findings, published recently online in the journal Blood, showed that the drug allows the body to accept the genes, which fight the ones inserted by viruses. Viruses are able to infect the body by inserting their own genetic material into human cells but gene therapy has developed  “gutted” viruses, such as HIV, to produce what are called “viral vectors".

Viral vectors carry therapeutic genes into cells without causing viral disease. Professor Torbett and other scientists have shown that HIV vectors can deliver genes to blood stem cells.

For diseases where abnormal cell function is triggered by DNA mutation, such as leukemia,  efficiently targeting the stem cells that produce these blood cells could be a successful approach to stalling the disease and prompting the body to produce healthy blood cells.

“If you produce a genetic modification in your blood stem cells when you are five years old, these changes are lifelong,” said Professor Torbett. 

Furthermore, it is thought that these gene-modified stem cells could develop into many types of cells that travel throughout the body to provide therapeutic effects. However, as cells have adapted defence mechanisms to overcome disease-causing viruses, engineered viral vectors can be prevented from efficiently delivering genes. 

Professor Torbett said that when scientists extract blood stem cells from the body for gene therapy, HIV viral vectors are usually able to deliver genes to only 30 to 40 per cent of them. For genetic diseases where treatment requires a reasonable number of healthy cells coming from stem cells, this number may be too low for therapeutic purposes.