$3m boost to Florey MND research

Pioneering projects exploring new treatments for motor neurone disease (MND) have been awarded more than $3 million thanks to funding from FightMND.

Professor Clare Parish, Dr Fazel Shabanpoor and Professor Brad Turner were each awarded $250,000 from FightMND to overcome barriers in research leading to failed drug development or failed clinical trials.

In separate funding, Dr Taide Wang was awarded a four year Early-Career Research Fellowship of $575,000, while Professor Turner received a further $2 million for a clinical trial investigating ambroxol.

Professor Parish will use stem cells from people living with MND to establish an advanced disease model recreating the specific types of motor neurons affected in the disease. She hopes that developing this model will lead to advanced preclinical drug screening capabilities and increase the likelihood of identifying promising therapies.

“With a long-standing history in working with human stem cells, this is the first time our team has used patient stem cell lines to study disease mechanisms in MND,” said Professor Parish.

“Human stem cells, derived from MND patients, provide a new way to look at aspects of the disease that are not achievable using non-human models. Our hope is that this could lead to a greater understanding of the disease progression, enabling new and better targeted therapies.”

In a separate project, Dr Shabanpoor will investigate TDP-43 – a protein vital to the health of motor neurons. In 97% of MND cases, TDP-43 behaves abnormally, contributing to death. His research will focus on developing and testing a gene therapy approach to overcome the accumulation of TDP-43 into clumps that are harmful to motor neurons, and the abnormal placement of the protein in motor neurons.

“Preventing the formation and accumulation of TDP-43 aggregates inside motor neurons holds significant therapeutic potential – applicable for treating many different forms of MND,” said Dr Shabanpoor.

“An exciting aspect of this project is the merger of two proven technologies – antisense and brain-penetrating peptides – to develop a new and safe therapy to treat MND.”

Further research will be conducted by Professor Turner to develop a new model of MND mimicking the most common genetic cause of the disease and addressing a key gap in current research. His team will create the model based on the C9orf72 gene – the most common genetic cause of MND – and test the effectiveness of potential drugs.

“Despite the discovery of C9orf72 mutations in MND over a decade ago, it remains unclear exactly how abnormalities in this gene trigger MND – hampering the development of treatments,” said Professor Turner.

“Developing a new and rigorously validated C9orf72 animal model will enable us to overcome previous challenges. It will become an invaluable resource to the global research community for testing disease hypotheses, pathology and therapeutic agents.”

Professor Turner also received funding of $2m to lead a world-first clinical trial investigating ambroxol as a treatment for MND.

Dr Wang was the inaugural recipient of the FightMND Angie Cunningham Scholarship in 2019 and has now been awarded an Early-Career Research Fellowship. He will investigate if modulating a unique cellular pathway that regulates the life of a cell, called ferroptosis, has therapeutic potential for MND.

His team aim to block ferroptosis in MND models using genetic tools and drugs that specifically target aspects of this pathway to delay the onset of the disease.

“The most exciting part about this research lies in the fact that the compounds we are investigating are safe and orally available, making them an effective yet non-invasive therapeutic strategy for treating MND. Our aim is to provide the clinical evidence needed to progress these therapies to clinical trials for MND,” said Dr Wang.

“This fellowship will support research to better our understanding of MND pathology, giving us invaluable knowledge to improve therapeutic targeting of ferroptosis for treating this debilitating disease.”