CMRI scientists have shown that you can use gene therapy to convert the liver into a “manufacturing plant’’ to produce a therapy to potentially treat diseases of the eye and kidney.
Dr Grant Logan and colleagues have had their work published as the cover story in the November issue of Human Gene Therapy. The team includes Gene Therapy Research Unit Head Professor Ian Alexander and scientists Amina Ahmad, Mawj Mandwie, Christine Smyth as well as their collaborators in the United Kingdom at the University of Cambridge and Imperial College London.
The work focuses on a key part of our immune system called “complement’’, which is a potent driver of inflammation. It normally functions to protect us from infection and is finely regulated through a complex interplay of “drivers” and “brakes”. But even subtle imbalance in favour of the “drivers” can cause illnesses such as age-related macular degeneration and some kidney diseases.
The challenge to developing treatments for these diseases are two-fold: restoring balance of the complement system and maintaining this over many decades of life. In this publication the authors show proof-of-principle how this can be achieved using a single infusion of an adeno-associated virus (AAV) vector to target the liver.
The team has been working on this project for seven years after Professor Alexander met co-author, the late Professor Sir Peter Lachmann, who was a leading authority on the complement system. One of Professor Lachmann’s accolades was to discover a natural “brake” that dampens complement activity. He was intent on using this knowledge to develop a therapy to restore balance to a hyperactive complement system to protect from disease.
“On first meeting Peter, Ian could see the merits of his ideas in regulating complement. However, Peter had not found a practical solution to address the problem of achieving this over many decades of life. Ian suggested that AAV gene therapy could be the answer” Dr Logan said.
“What we’ve done though this paper is shown how a very complicated part of the immune system could be regulated through gene therapy. We were actually using the liver to increase the blood levels of Peter’s natural “brake”. We showed this dampened complement activity and we saw evidence of these effects in the blood and kidneys.’’
Dr Logan said this publication was an excellent example of the exciting things that can be achieved through collaboration of teams with unique skill sets.
“We have combined the UK team’s advanced knowledge of the complement system with our expertise in gene delivery to regulate the complement system over the long-term after a single treatment.”
“It shows that we can use the power of AAV gene therapy to convert the liver into a manufacturing plant, such that the body’s own tissues provide the therapeutic protein. This negates the need for regular infusions of the “brake” and potentially provides a long-term solution to the challenge of permanently protecting tissues under inflammatory attack.”