Research Directions | February 2024

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.

Monepantel
PharmAust is an Australia pharmaceutical company that has been trialing the drug Monepantel as a possible MND treatment. Monepantel is a well-known veterinary drug that targets protein build-up in neurons. Phase 1 of this trial involved testing different doses of the drug and is now complete. Twelve patients were enrolled in the Phase 1 study and they are all now moving into an Open-Label Extension (OLE) phase. The Phase 1 study was small and there was no placebo to compare against. However, to date, all patients involved in the study have survived 12 months, which is a promising outcome. The company is now looking to commence a Phase 2 study to investigate the treatment in a larger group of patients.

RADICAVA
Edaravone is the active ingredient in a treatment that is sold under the product name RADICAVA®. On the 15th of February 2023, the Therapeutic Goods Administration (TGA) in Australia approved RADICAVA® for the treatment of ALS in Australia. Teva Pharma Australia, who have been licensed to market the product for use in Australia, applied to the Pharmaceutical Benefits Advisory Committee (PBAC) to have RADICAVA® listed on the Pharmaceutical Benefit Scheme (PBS) for eligible people with ALS in Australia. TEVA have stated RADICAVA® will be made available in Australia only after it is listed on the PBS. The initial application to the PBAC was unsuccessful, however TEVA have resubmitted their application with the outcome due in March 2024.

The ADORE clinical trial is a Phase 3 trial investigating FNP122, which is the oral form of edaravone (rather than the infused form above). Results released in January showed the trial did not meet its primary or secondary endpoints, with no significant difference in the change in ALSFRS-R for those who received the treatment compared to those who received the placebo. There was also no improvement in long-term survival when comparing FNP122 to placebo over 72 weeks of treatment. This data suggests that FNP122 is not beneficial for people with MND. This is a different drug to RADICAVA, however it does emphasise that edaravone is not likely to provide huge benefits to people with MND.

Promising early results from Macquarie University
Professors Yazi Ke and Lars Littner from Macquarie University published their data showing that a specific protein, 14-3-3, is a key player in the toxic clumps formed by TDP-43 in MND. They found that targeting 14-3-3 could help to break up these clumps and act as a “vacuum-cleaner”. Although this has only been tested in animals and cells so far, the team have now been funded by FightMND to take these studies forward into human trials. This work was initially funded by MNDRA and it is very satisfying to see it move forward towards testing in humans.

MND Research Collective
The MND Research Collective Clinical Care team have published an article reviewing the complexity involved in providing multidisciplinary respiratory care in MND. The review discussed how all members of the multidisciplinary team contribute to collective decision-making in MND, how the sum of the parts is greater than any individual care component or health professional, and that multidisciplinary care provides benefit to the person living with MND.

Smoking risk factor in MND
Another study has demonstrated that smoking presents a risk for developing MND. There have been a number of studies now that have shown this link. This is quite unsurprising given the huge weight of evidence that smoking is toxic for many cells and biological processes. The value of these studies is difficult to discern unless scientists can pinpoint the mechanism by which smoking may contribute to MND. Until that time, it is best to encourage everyone to avoid smoking, and ensure we spend valuable MND research funds on more useful studies.

Mitochondrial function affect on MND
It is well-established that defects in mitochondria (cell powerhouses) play a key role in MND. This study looked at genetic changes in the genes that control mitochondria to see their effect in MND. They showed that defective mitochondria affect how long people with MND live with the condition, but not how likely they are to develop the disease in the first place. They also discovered the existence of a mutation that seems to protect nerve cells, helping people with MND live longer. This suggests targeting mitochondrial function could mitigate disease severity, offering a new direction in MND therapy.

Australia Day honours
Congratulations to Professor Julian Gold for his award as a Member (AM) in the general Division in the 2024 Australia Day Honours. Julian has been the driving force behind testing combination anti-retroviral therapy (Triumeq) in patients with MND - the Lighthouse Trials.

State of Play
Don’t forget the next State of Play: How tech research can help living with MND. MND Australia's Dr Ben O'Mara will talk about the 'Game on with MND' project looking at how we can make gaming more accessible for people with MND and Dr Taylor Dick from the University of Queensland will talk about exoskeletons as mobility aids.