New treatment hope in Parkinson’s breakthrough

Melbourne researchers investigating the cause of Parkinson’s disease have made a breakthrough, sparking hopes of fast-tracked treatments.

Medical experts hope to be able to fast-track treatments for Parkinson’s disease.

Melbourne researchers have cracked a mysterious critical process that causes Parkinson’s disease to progress, a finding they hope can fast-track treatments for the incurable disease.

The breakthrough, a culmination of eight years of work, has seen researchers create a molecular “live action movie” of the entire workings of this key protein, so they can better understand how it starves brain cells of energy when they are defective, causing them to malfunction and die.

This neurodegenerative process is the hallmark of damage to dopamine-producing cells in many types of Parkinson’s disease, particularly those with an early-age onset.

The findings from the Walter and Eliza Hall Institute of Medical Research provide the first detailed blueprint of the key disease-causing process, which they hope will lead to new treatments to slow or even stop its progression by “switching on” protective factors in these brain cells.

Lead researcher Professor David Komander said different microscope techniques over the past decade had allowed molecular “snapshots” to be taken of the key proteins behind the disease. But these static images did not reveal what was driving cell death, a process that is particularly relevant for the most important protein called PINK1.

“These snapshots did not fit together,” Prof Komander said.

“It was like taking a snapshot of a mountain on holiday, and then you take another snapshot of the other side. You’re missing that context to understand this is the same mountain.

“In our new work we’ve fixed that and explained how the entire process happens; from when PINK1 is initially made, to how defects in the protein lead to Parkinson’s disease.”

The “molecular movies” they created by using a new type of imaging called cryoelectron microscopy, saw them stitch the snapshots together to reveal that this protein allowed a “protective switch” within the cell to be turned on.

“If there is a damaged energy component in your cell, you are going to flick in the switch so this damage can be removed,” he said.

“If you do not have that switch, then your cells will accumulate this cellular rubbish at a high rate. That is particularly bad for neurons.”

The findings, which were also led by PhD student Zhong Yan Gan, were published in the prestigious journal Nature.

Ten million people worldwide – including about 80,000 Australians – have Parkinson’s, and there are no drugs to stop the tremors, muscle stiffness and speech changes.

But Professor Komander said Parkinson’s disease was not one disease, instead more like cancer with different types, causes and optimal treatments.

Given this, the next part of the research will see them genetically analyse newly diagnosed Victorian patients to uncover what triggers their particular disease, in the next step to developing new treatments.

“Our long term plan is to map the problems in individuals to turn this into a more individualised treatment option for a patient,” he said.

“We need to first understand what is it that we can change in order to side step how the protein needs to be activated, despite being broken, like finding the missing part to the machine.”