IHMRI researchers have found that copper may not protect all MND causing mutants in the SOD1 gene
IHMRI Senior Research Assistant Natalie Farrawell has teamed up with Professor Justin Yerbury and his daughter Maddison Yerbury on a paper which has led to a new discovery for copper based drugs used in Motor Neurone Disease (MND) treatment trials.
The paper investigates the protective effects of the compound CuATSM in laboratory grown cells that mimic the SOD1 inherited form of MND also known as Amyotrophic lateral sclerosis (ALS).
The compound is currently in clinical trials in a number of sites across Australia.
The research discovery was accepted and published in ACS Chemical Neuroscience last month.
Ms Farrawell’s paper has also been awarded the IHMRI publication of the month for November. It’s her second IHMRI publication of the month win this year.
Supervisor and mentor, Professor Justin Yerbury says the findings are significant for future trials in patients with MND.
“The results of this in vitro study highlights that subtle genetic differences may affect the outcomes of particular drugs for MND patients,” said Professor Justin Yerbury.
“This is important, because if genetic differences are not taken into account in trial design, drugs may fail at clinical trial even though they may be more beneficial to some individuals.”
Ms Farrawell’s paper suggests that CuATSM may not be effective against all mutations of the SOD1 gene.
“There are over 150 different mutations in the SOD1 gene which cause various effects to the SOD1 enzyme structure including the ability to bind metals and benefit from the protective effects of CuATSM. Future work looking at the effects of CuATSM in animal models will be important to confirm our findings,” she said.
CuATSM is a molecule which has been used in imaging experiments to locate tissues within a person’s body that are not receiving sufficient oxygen. These tissues have also been found to have damaged or dysfunctional mitochondria.
Neuroscientists became interested in CuATSM as a potential therapeutic agent after they found it has the ability to deliver copper safely to specific cells within the body which may prevent the malformation of proteins known to cause neurodegenerative diseases.
Copper-ATSM therapy was developed in Australia in 2008. Research has shown copper-ATSM can protect motor neurones in the spinal cord, improve MND-like symptoms, and extend the lifespan of mice with a mutated form of SOD1.
A human trial of the drug began in Australia in 2016 and finished this year.
Phase 2 of the trial is expected to determine the effect of CuATSM on disease progression in MND patients.
It is hoped this new research discovery will enable scientists to narrow down which mutations in the SOD1 gene will be most effectively impacted by CuATSM.
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Louise Negline, Communications Coordinator
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Top photo: Natalie Farrawell and Professor Justin Yerbury. Photo by Mark Newsham.