Foundation grant keeps research momentum going. 

A rare genetic disease that stops children’s brains from turning fats into fatty acids means a lifetime of difficulty for patients and their families. These children lose motor control, develop severe spasticity and intellectual disability, and there is no treatment.

Brisbane researcher Dr Merja Joensuu is challenging fundamental assumptions about the way the human brain uses fat for energy production. With enough funding, her work could lead to treatments for the disease hereditary spastic paraplegia (HSP) type 54.

Already, Merja has shown, in animal models of this disease, that replacing missing fatty acids reverses majority of the effects. Moving toward a treatment for children means first proving it holds true in human cells, but funding for her research through the NHMRC Investigator Grant program has been elusive, despite her application being highly ranked.

That is where the new Near-Miss Funding Program from the Foundation together with the Australasian Society for Stem Cell Research (ASSCR) comes in. They are backing Merja with a $100,000 grant to continue and strengthen her research at the University of Queensland’s Australian Institute for Bioengineering and Nanotechnology.

For decades, neuroscience had assumed the brain ran on sugar alone, treating fat as mere structural scaffolding. 
Merja’s team found otherwise: neurons, they discovered, quietly burn their own fat for fuel. 

An enzyme called DDHD2 releases a steady flux of long-chain fatty acids inside neurons, supplying around a fifth of their everyday energy — and even more when the brain is working hard.

“For neurons in the brain, the field had long concluded that fatty acids aren’t used for energy,” Merja says.

“We figured we’d test that out again, with all the techniques now available to us.”

The findings, published in Nature Metabolism, overturned received wisdom about how the brain powers itself.

“Rare and ultra-rare diseases often go unnoticed by society,” Merja says, “but that doesn’t mean the effects on patients and their loved ones aren’t very strong and impactful.”

It’s also, she believes, where some of the most fundamental discoveries hide. “By studying this ultra-rare disease, we learn something fundamental about all of our brains. I think that often gets neglected and overlooked.”

In the lab, restoring these lost fatty acids works fast: within 48 hours, mouse neurons regain their energy and reverse a cascade of related problems in membrane trafficking, mitochondria and protein processing. “It’s basically giving back what was lost,” she says.

It is, as far as her team can tell, the first therapeutic strategy ever proposed for this disease.

With bridging support from the Near-Miss Funding Program grant, Merja is building the first human stem cell model of HSP54, using CRISPR gene editing and, where possible, cells donated through international patient advocacy groups.

Although the research will take years, Merja is optimistic.  “I think this is the first therapeutic approach of its kind for this disease, or any similar disease. I think it’s very promising,” she says.

The implications may reach further still. Energy failure in neurons is also a feature of Parkinson’s, Alzheimer’s and motor neurone disease.

“I think it has huge potential — not only for our subset of HSPs, but other HSPs and other neurodegenerative diseases that have a problem with energy,” Merja says.