MJD Foundation

Zebrafish Study

Zebrafish study offers hope to MJD sufferers

Exciting results are emerging from the Zebrafish research conducted by Dr Angela Laird and PhD student Maxinne Watchon at the Brain & Mind Institute in Sydney.

MJD Foundation Chairman, Neil Wesbury, said "Our families and the communities that support them want nothing more than to live lives free of Machado Joseph Disease. Alongside the MJD Foundation, they have been steadfast in their support of research that works towards this goal - through the Anindilyakwa Land Council the Traditional Owners of Groote Eylandt displayed great vision in providing critical initial funding for this project. Dr Laird and her team have made an enormous contribution to understanding the disease by establishing the first transgenic zebrafish models of MJD, creating the opportunity for rapid drug test models. Being able to prove that the movement of fish affected by MJD can be improved is a significant breakthrough and provides vital hope that this can be translated into the same outcomes for people with MJD. We are excited at the potential for taking this research further and working toward establishing a treatment for people who have MJD."

The full article written by Amos Aikman and published in The Australian on 9th August can be read below. 

Zebrafish
Researchers working with tiny zebrafish identified a substance they think could
help the body clear itself of toxic disease-causing proteins. Picture: Toby Zerna

Sufferers of a rare genetic condition that traps people in their bodies are a little closer to treatment after researchers working with tiny zebrafish identified a substance they think could help the body clear itself of toxic disease-causing proteins.

The approach, which relies on stimulating autophagy — a means of naturally recycling cellular components — could also help those with other neuro-degenerative disorders such as Parkinson’s and motor neuron disease.

Macquarie University scientists have been studying Machado-­Joseph disease, an inherited condition that disproportionately affects indigenous people, particularly those in remote parts of the Northern Territory including Groote Eylandt. About 100 people live with MJD today, and a further 650 are considered at risk of developing the condition.

The researchers implanted the human gene known to cause MJD into zebrafish, a transparent species that develops quickly and absorbs drugs from water.

Their “transgenic model” allowed them to observe how MJD developed over the fish’s lifespan, said Angela Laird, who led the project. Her team, including Sydney University PhD student Maxinne Watchon, found that adding a substance called calpeptin to the fish’s water caused their bodies to re­cycle most of the toxic protein responsible for MJD-like symptoms.

“Results were more prom­ising than we had anticipated. The calpeptin didn’t just remove fragments of the disease-causing protein but the whole protein,” Dr Laird said.

“Once the disease-causing protein was removed, we saw improvements in the movement of zebrafish with MJD.”

Neil Westbury, who chairs the MJD Foundation that supports sufferers, said they and their families “want nothing more than to live lives free of MJD”.

“Through the Anindilyakwa Land Council, the traditional owners of Groote Eylandt displayed great vision in providing critical initial funding for this project,” he said. “Dr Laird and her team have made an enormous contribution to understanding the disease.”

While calpeptin itself may never become a treatment due to long drug development cycles, Dr Laird’s transgenic zebrafish model should speed the hunt for a cure among existing drugs.

The research is published today in The Journal of Neuroscience (Download here).

The 2016 Nobel Prize in Medicine was awarded to Yoshinori Ohsumi for his work on the mechanisms of autophagy in the early 1990s.