One step closer to helping cure genetic diseases

22 June 2017

 An important discovery published  in Nature Genetics will make gene therapy--which is already helping to cure genetic diseases--safer and more effective for children. The discovery by Prof Ian Alexander, Head of the Gene Therapy Research Unit, a joint initiative of CMRI and Kids Research Institute, and his team  will help improve gene therapy in the future.

in key organs such as the liver, there are the gene transfer tools used to replace or repair faulty disease-causing genes—AAV vectors. AAV vectors are like miniature Trojan horses that are used to carry healthy copies of genes into cells and even microscopic repair kits that can fix errors in DNA.

These vectors are safe because they are derived from a naturally occurring AAV virus. “Up to 70% of people have been exposed to naturally occurring AAV already and suffer no ill effects,” said Prof  Alexander, When giving gene therapy to children, safety is a top concern. Professor Alexander and his team have identified a small region in naturally occurring AAV that can sometimes have negative effects on liver cells.

“Knowing what this region of AAV does provides us with a new way of measuring the small risk associated with gene therapy in the liver, and will allow us to more accurately balance risk against likely benefits, “ said Prof Alexander.

While gene therapy is already helping patients internationally overcome genetic diseases,  gene therapy treatments still need to be tailored to the thousands of conditions where this approach offers the prospect of effective treatment.

It is hoped that this research will help children like two year old Charlize and her twin brother Isaac who were both born with a rare and severe metabolic disease called Propionic Acidemia. Those with the disease have trouble breaking down and using amino acids from food, causing problems with appetite, low muscle tone, low platelets and white blood cells. They are missing a vital enzyme which causes toxic and harmful substances such as ammonia and propionic acid to build up in their blood.  If the illness cannot be controlled they go into a metabolic crisis which can cause breathing problems, seizures, swelling of the brain, stroke and coma leading to death.

Isaac underwent surgery for a new liver, which is supposed to make enough of their missing enzyme to help them have a much more normal life. But after surgery, he had a mass bacterial infection and went into septic shock. Sadly, in January this year, Isaac passed away. Now his twin sister, Charlize, is on the transplant list as she awaits a new liver.

 “Now we’ve identified this element, we can edit it out of our AAV vectors. Which is important when clinicians want to treat brain diseases but not affect the liver, for example. This means increased specificity as well as safety.”

There are currently a 130 registered AAV clinical trials globally, with over 2000 patients treated, so far and this will only grow in future. Prof Alexander’s work will help ensure that research produces safe as well as effective cures for genetic diseases. And the sooner such treatments are available for children like Charlize the better.


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