Welcome to the MNDRA research update. In this report we will highlight outcomes and advances from the MND research world that have caught our attention over the last few weeks.
The 3rd Australian and New Zealand MND Research Symposium was held in Melbourne on the 27th and 28th of August and was a great success. We had a record 300 registrants, with the most lived experience attendees to date. Highlights included presentations from world-leading international researchers, a number of talks from people with MND, ground-breaking research from fantastic Australian researchers and some great debates. Recordings from the Symposium can be viewed on our Youtube channel.
Our research funding grant round closed on the 2nd September and we had 60 applications which are now out to review with our expert researchers to ensure we support only the best ideas and research. We will announce the outcomes in November.
Insurance and genetic testing
The Federal government has announced a total ban on the use of adverse genetic testing results in life insurance. This means that life insurers and those offering income protection and permanent disability insurance will be banned from using genetic testing to refuse cover, or hike up charges, for a range of insurance products. This brings Australia in line with other countries such as Canada and the UK, who have had such legislation in place for years or even decades.
This is a critical outcome for the MND community. With a number of mutations already known to contribute to MND, and treatments becoming available targeting them, it is imperative that MND patients and their families are not risking discrimination by testing their genetic status. The total ban will be subject to a five yearly review.
“We know that the fear of being denied insurance coverage has been a huge disincentive for Australians to have genetic testing when they need it. Seeing this situation fixed is an enormous step forward for health care in this country," The Australian Medical Association President, Professor Steve Robson.
MND diagnostic biomarker
Several papers recently published have identified what could turn out to be the first MND diagnostic marker.
Researchers across the world working in several consortia have co-discovered a potential new biomarker for MND that may act as the first specific diagnostic marker. The HDGFL2 protein, which interacts with TDP-43 (which is dysfunctional in up to 97% of MND cases) has been shown to have an extra piece of protein (a “cryptic peptide”) in samples from MND patients.
Cryptic HDGFL2 can also be detected in blood of individuals with MND–FTD, including in pre-symptomatic C9orf72 mutation carriers.
New information on how FUS might cause MND
Two studies recently published have provided some insights into how FUS, one of the genes known to contribute to MND, might trigger the MND disease process and also how it could be targeted for treatment.
Frontotemporal dementia‑like disease progression elicited by seeded aggregation and spread of FUS
RNA binding proteins, including FUS, play a role in MND and about 10% of sporadic FTD. In this study they injected human FUS fibrils into brains of mice which had their mouse FUS gene replaced with either a normal human FUS gene or one carrying the mutation that is thought to contribute to MND.
They showed that if they injected fibrils into mice carrying the mutated FUS gene, then the FUS fibril caused a an FTD-like disease, causing neurodegeneration and affecting cognition in the mice. This is the first time that such a spread of neuronal damage has been shown in an animal model and provides some good insights into how the disease might progress in humans.
Engineered NLS-chimera downregulates expression of aggregation-prone endogenous FUS
Another group has been working on how they might stop the aggregation of FUS. There is a group of proteins called nuclear import receptors (NIRs), whose job is to help stop other proteins like FUS and TDP-4 from aggregating and causing disease. However, the mutations that occur in FUS and TDP-43 in MND stop them interacting with NIRs.
In this study, the researchers found that they could create a specially engineered form of FUS that could be transferred into cells to help them interact with NIRs, reducing the level of FUS in the cell. The next step is to see how this can work in MND disease models, but it does provide a potential mechanism to stop protein aggregation in diseases like MND.
