The blood-brain barrier strictly controls what can enter the brain to prevent toxins and infections from passing through. It is essential to maintaining the brain’s overall health.

But this barrier is so fiercely protective, it also blocks around 98% of cancer drugs from entering the brain.

Chief Investigator Professor Guillaume Lessene said treatment options are particularly dire for patients with glioblastoma and diffuse midline glioma.

“Brain tumours represent a leading cause of cancer-related death in Australians aged under 40,” Prof Lessene, a Division Head and Associate Director of Therapeutic Discovery at WEHI, said.

“Therapies that have driven breakthroughs in other cancers offer little hope for these patients, meaning survival rates for brain cancer have barely shifted in decades.

“Our project will deploy a revolutionary strategy to deliver drugs directly into the brain and tackle the problem at the source – the formidable blood-brain barrier.”

The project is a collaboration between some of Australia’s leading researchers and clinicians, with the MRFF funding complemented by contributions from WEHI and support from Carrie’s Beanies 4 Brain Cancer Foundation.

The Brain Cancer Centre was founded by Carrie’s Beanies 4 Brain Cancer and established in partnership with WEHI with support from the Victorian Government.

The centre has provided $1.88m over four years in seed funding, which has been instrumental to establishing and progressing this research program.

The brain needs a steady supply of essential nutrients, like iron and glucose, to support its healthy growth and development.

To get these nutrients, the brain uses a range of natural delivery systems that transport them from the bloodstream into the brain.

Cells in the blood–brain barrier contain specialised ‘docking stations’ that recognise these nutrient‑carrying proteins and actively draw them into the brain.

Lead investigator Associate Professor Jim Whittle said this barrier has long stood in the way of effective treatments for brain cancer patients.

“We want to hijack these delivery pathways to smuggle cancer-killing molecules into the brain,” said Assoc Prof Whittle, also a WEHI laboratory head, neuro oncologist at Peter Mac, and co-head of Research Strategy at The Brain Cancer Centre.

“The blood-brain barrier is remarkably selective, but it always lets these nutrients in.

“We’re taking advantage of that to deliver drugs in a form the brain is programmed to accept.

“Our ultimate goal is to unlock a new class of drugs while also creating the first real opportunity to test existing drugs that have failed to reach the brain to-date.”

As part of the project, researchers will develop nanobody‑drug conjugates – tiny antibody fragments that can deliver drugs more precisely, while minimising harm to healthy tissue.

Nanobodies that can bind to the transferrin receptor will then be designed, providing a unique way to ferry drugs into the blood-brain barrier by leveraging the iron transport system.

It’s the first time a research group will use this approach to deliver cancer drugs directly into the brain.

Minister for Health and Ageing Mark Butler said the project consolidates Australia’s proud record of world‑leading medical research, driven by collaboration and innovation.

“Bold and innovative research like this is needed to spearhead better treatments for brain cancer,” he said.

“This investment is another example of our government’s commitment to accelerating health and medical advances by supporting breakthrough research that pushes boundaries.

“Too many families know the pain of brain cancer. This project has the potential to open an entirely new frontier in brain cancer treatment that could change the story for thousands of Australians.”

Professor Kate Drummond, Director of Neurosurgery at the RMH and lead investigator, said that outsmarting the blood-brain barrier is a challenge no single laboratory or research team could solve.

“The blood brain barrier remains one of the least understood and under-researched biological structures in the human body,” Prof Drummond said.

“To really change this and give patients the improved treatments they deserve, we need the type of breakthrough ideas and national coordination that underpins this research collaboration.”

Researchers from MIPS and Peter Mac will play critical roles in assessing the druglike properties of the nanobody-drug conjugates and in developing the nanobodies for therapeutic application.

The team hopes to identify a clinic-ready glioma target within the next five years and establish a national platform to develop the ​next generation of brain-penetrating drugs​ over the subsequent years.

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Lead investigators Associate Professor Jim Whittle and Kate Drummond and Chief Investigator Professor Guillaume Lessene.