A gene therapy project to save infants’ lives has been named the top-ranked National Health and Medical Research Council (NHMRC) Ideas Grant for 2020. The project led by Professor Ian Alexander and his team were awarded the 2020 NHMRC Marshall and Warren Ideas Grant Award at the NHMRC Research Excellence Awards Dinner on June 16th.

Professor Ian Alexander, Head of the Gene Therapy Research Unit, a joint initiative of Children’s Medical Research Institute (CMRI) and The Sydney Children’s Hospitals Network (SCHN), and Professor in Paediatrics and Molecular Medicine at the University of Sydney. His team’s work, over more than 25 years, has made significant contributions to the field of gene therapy and is now leading major advances in treatments for life-threatening genetic diseases.

This is proof that we weren’t just dreamers and symbolic of the power of the genomic revolution – Prof Ian Alexander

Gene therapies are ‘genetic medicines’ where healthy copies of genes are delivered into diseased cells to replace or repair faulty genes and therefore treat (or potentially cure) disease. The delivery vehicle for the healthy gene is called a vector (typically modified viruses such as adeno-associated virus (AAV)).

This three-year NHMRC-awarded project aims to exploit immunity to the AAV vector that is stimulated in infants receiving gene therapy for Spinal Muscular Atrophy (SMA), and to use this to engineer the next generation of vectors.

SMA is an inherited neuromuscular disorder, which can be fatal. Babies often die within the first 2 years of life. NSW/ACT is one of the few places in the world where there is now pilot newborn screening for SMA, supported by the NSW Government.

The clinical team at SCHN (incorporating experts from The Children’s Hospital at Westmead and Sydney Children’s Hospital, Randwick) has become a leading global centre in using AAV-based viral vectors in gene therapy for infants with SMA, with unprecedented success.

Prof Alexander said:

The gene therapy field is coming of age and earning the scientific respect that it has increasingly deserved. I thank the NHMRC for this award, which is emblematic of the explosion of therapeutic possibilities - which are unlimited.

This award is linked to the fact that we are at the front end of seeing the impact of the genomic revolution,’’ Prof Alexander said. “It is heralding our ability to treat disease by gene transfer. The most stunning example being the treatment of SMA in infants.

We are now trying to go beyond that. This takes it a step further to improve the technology available to patients – to be able to treat more children, and not just children with SMA. The success of the SMA trials is not the end, it’s just the beginning. There is so much powerful science that can be leveraged by this progress.

The team is now looking at ways to identify what antibodies the children are producing against the SMA gene therapy vector, recover these antibodies by reverse engineering, and to use these antibodies to guide re-engineering of efficient AAV vectors that can evade immunity. This would help the proportion of children who develop natural immunity to AAV and for whom the original SMA gene therapy is therefore ineffective.

In this way we can use a child’s immune response to both improve the technology and enhance the treatment opportunities,’’ Prof Alexander said. “This is a very powerful approach that has many implications, for neurological conditions and beyond.

Success breeds success. There is a very fertile interface between clinical medicine and discovery science, and this shows that deep science can emerge from privileged access to clinical material.

The project’s other lead investigator is Dr Grant Logan from Children’s Medical Research Institute. Associate investigators are Associate Professor Leszek Lisowski (CMRI), Associate Professor Michelle Farrar (SCHN and the University of NSW), Professor Daniel Christ and Dr Joanne Reed (Garvan Institute for Medical Research), and Dr Denis Bauer (CSIRO).

This award comes days after Children’s Medical Research Institute and The Sydney Children’s Hospitals Network announced the establishment of the Australian Genome Therapeutics Centre to fill the gap between advances in genomic diagnosis and therapeutic benefit for patients. 

Read more about the Australian Genome Therapeutics Centre.