Scientists at La Trobe University have received nearly $140,000 from rare disease charity Archie's Embrace to investigate an under-researched genetic disorder which causes early-onset neurodegeneration in babies.
The disorder, which causes a deficiency of the enzyme ECHS1, leaves the body unable to digest and use certain amino acids and fatty acids – crucial nutrients which provide the body with the energy it needs to grow.
Archie's Embrace Director Ros Melling hopes the research will open doors to finding new ways of improving symptoms, decreasing suffering, and increasing lifespan for children who have ECHS1 deficiency.
"Gaining the science and research and strengthening knowledge on how to improve quality of life for these children is powerful. Many parents are told at the time of diagnosis that there is little hope, as there is currently no treatment. Research and data are limited, and this is what is needed to change treatment at the patient face by medical teams," Ms Melling said.
Research leader Dr Travis Johnson and postdoctoral researcher Dr Sarah Mele, from the La Trobe Institute for Molecular Science (LIMS) and the School of Agriculture, Biomedicine and Environment, said their aim is to gain a better understanding of the disorder to open avenues of research for new treatments.
"ECHS1 deficiency affects so few people, which makes it near impossible to devise and test treatments in the clinic. The ECHS1 enzyme has emerged as a critical player in several aspects of metabolism and this has made it difficult to pinpoint the precise causes of the disorder. Understanding these is critical for treatment development," Dr Johnson said.
The project will see the research team use fruit flies, which share 75 per cent of disease-causing genes with humans, including the ECHS1 gene which has been altered for the study.
The flies will be used to test for different drugs and synthetic diets, and to find other genes which interact with the ECHS1 gene.
"Treatments that have been tried so far that would logically make sense for ECHS1 haven't been working, and we don't know why. We hope that this research will uncover possible new treatments as well as provide hope for those affected by ECHS1," Dr Mele said.
ECHS1 deficiency affects less than one in 250,000 babies and children annually, and is one of more than 1400 rare Inherited Metabolic Disorders (IMDs).
Stemming from genetic mutations passed down from the baby's parents, ECHS1 deficiency leaves the body unable to break down and use the amino acid Valine as well as essential fatty acids – both growth-promoting nutrients delivered to the body via food.
When the body is unable to break these nutrients down, not only does it not have enough energy to grow, it also experiences a toxic build-up of Valine compounds. As a result, the structures in the body and brain begin to degenerate.
"The disorder affects all the body systems you can possibly think of that are associated with growing – feeding, movement, even mood. All these key early milestones unwind," Dr Mele said.
Symptoms of ECHS1 deficiency often appear suddenly within the first few years of a child's life.
For Ms Melling's son Archie, after whom Archie's Embrace is named, it was 13 months before symptoms of the disorder appeared.
"Archie had been getting all his milestones. He walked, he talked, he ate, he laughed – always laughing," Ms Melling said.
It was a bout of gastro that triggered the disorder, which until then had been dormant. After having difficulty breathing overnight, he collapsed and was rushed to hospital.
After ruling out other causes, the medical team began investigating metabolic and genetic causes for his illness.
"Eventually, we got to the point of needing to do genetic testing. After about a week they gave us a diagnosis of Leigh Syndrome, but it took six months to get the exact ECHS1 deficiency diagnosis," Ms Melling said.
Archie is now eight years old. He's still a happy and bubbly child, but is quadriplegic, non-verbal, suffers pain from severe muscle spasms, and must be fed a specialised diet through a tube.
He also takes several medications and vitamins to alleviate symptoms of ECHS1 deficiency, but a lack of research means that there is no treatment for the disorder, and limited resources to help families learn about and manage it.
After connecting with other impacted families via social media, Ms Melling established Archie's Embrace to raise funds for rare disease research.
The charity has already funded research overseas for ECHS1 deficiency. They will fully fund the upcoming project at La Trobe University, providing $138,545 to investigate possible treatments to alleviate symptoms.
"We're very grateful to Archie's Embrace for funding this much-needed research. It's a fantastic start, and we hope that by shedding more light on ECHS1 deficiency, we can raise awareness both here and overseas so all possible options can be explored for these kids," Dr Johnson said.
The research will be conducted in the next year, in collaboration with Professor Matthew Piper at Monash University.
