Drug company deal delivers hope for dementia

A drug discovery company co-founded by Kiwi Professor Chris Shaw has announced a landmark multimillion-dollar deal with a pharmaceutical company for a potential treatment for frontotemporal dementia.

UK-based gene therapy firm AviadoBio has partnered with Japanese pharmaceutical giant Astellas for exclusive rights to license a gene therapy called AVB-101 that could halt the progression of a genetic form of frontotemporal dementia.

AviadoBio will receive an upfront investment of USD$30 million to extend human clinical trials, as part of a potential USD$2.18 billion deal.

“We are finally delivering on a promise made to our patients - that genetic discoveries would lead to transformative genetic therapies,” says Professor Shaw, who is the inaugural Hugh Green Translational Chair in Neuroscience at the University of Auckland’s Centre for Brain Research.

“We’ve been working on using gene therapy to treat neurological disease for years, but the advances that could result from that amount of investment would be phenomenal.”

Frontotemporal dementia is a devastating form of early-onset dementia that typically leads to death within three to 13 years from diagnosis.

People with frontotemporal dementia commonly experience a rapid decline in executive function (attention control, working memory, problem-solving), uncharacteristic behaviours, loss of language, apathy, and reduced mobility.

It is an important cause of dementia in those under the age of 65 and is often under-recognised, and misdiagnosed.

Shaw has spent more than 30 years in the UK as Professor of Neurology and Neuroscience at King’s College London, and he co-founded the spinout company AviadoBio to raise the substantial funds needed to bring his lab’s ground-breaking gene therapies to patients.

Shaw’s lab at King’s College is well-known for identifying several genes responsible for motor neuron disease and frontotemporal dementia, some of which are the target of new drugs in the company’s pipeline.

He currently shares his time between the Centre for Brain Research in New Zealand and the UK, where he continues his roles at King’s College and AviadoBio.

Gene therapy uses a tiny modified virus to deliver a package of DNA, capable of supplementing or silencing specific gene targets. In the case of AVB-101 the virus is delivered directly into the brain to rescue cells damaged by loss of the GRN gene.

What is unique about this neurosurgical approach is that it uses the natural neuronal network to deliver the missing protein throughout the brain.

The GRN mutation is the cause of frontotemporal dementia in an estimated five to ten percent of cases; however, it is one of the more common genetic causes of frontotemporal dementia, as most cases are not linked to identifiable genetic mutations.

AVB-101 gene therapy has shown promising results in cellular and animal studies, successfully reversing pathology. An early human clinical trial is also under way and three patients have already been treated.

“It is too early to see beneficial results but the aim is to halt frontotemporal dementia in its tracks,” Shaw says.

“In some ways, this is a very niche therapy, but this gene supplement approach has the potential to be applied across a broad range of neurological diseases.

"There is a whole pipeline of other therapies that could be brought to clinical trial on the back of this.”

Shaw explains that crossing the blood-brain-barrier is a significant hurdle for delivering gene therapies to damaged brain cells.

“In the case of gene silencing, for the treatment to be effective the virus has to infect nearly every cell it needs to save which is a huge challenge.

"New viral vectors are being developed that can cross the blood-brain barrier and have the potential to supplement or silence genes in the majority of neurons in the brain and spinal cord.

"If these new vectors are safe they have the potential to transform gene therapy for neurological disorders.”