Cure for MND Clinical Trials

Dedicated to funding promising new therapies in clinical trials for Australians living with MND

Click on the tabs below to read about current and upcoming Cure for MND funded clinical trials

Copper ATSMThe first Phase 1 clinical trial of Copper-ATSM as a potential treatment option for Motor Neurone Disease (MND) will start in 2016. Cu-ATSM therapy was developed in Melbourne Australia, and the trial is a true example of Australian scientific ingenuity and innovation, and demonstrates the calibre of MND researchers we have in this Country. To bring this trail to Australia, we are proud to partner with a USA company called Collaborative Medicinal Development (CMD). We are very excited by the basic scientific work and the pre-clinical trials and data that have lead to this first-in-man clinical study in Australia.

An overview of the research that has been performed to date, the rationale for why this compound may be an effective treatment, and the status of the clinical trial is briefly summarized below.

A brief history of the research

The drug is copper-ATSM. Its chemical name is diacetylbis (4-methylthiosemicarbazonato) copper but is often abbreviated to Cu-ATSM or Cu(II)ATSM. In 2005, Anthony White, Kevin Barnham and Paul Donnelly at The University of Melbourne first began discussing the potential to treat neurodegenerative disease by using Cu-ATSM.

Skipping forward to 2008 was the first time copper-ATSM was given to specifically bred mice that develop symptoms that mimic human Motor Neurone Disease (MND). About 10% of all MND cases are familial, which means the disease-causing genes can be passed on from parent to child. Mutations in one of these particular genes affects superoxide dismutase-1 (SOD1) which accounts for a large proportion of familial or inherited MND. The mice most commonly used to study MND in the laboratory that develop MND-like symptoms are genetically engineered to carry this mutation, and hence until recently were our best means of testing potential therapeutics.

Although the first study to test copper-ATSM in mutant SOD1 mice took many months to complete, the outcomes were very clear: treating with copper-ATSM protected motor neurons in the spinal cord, improved the animal’s MND-like symptoms, and extended lifespan of the mice. These outcomes were published in 2010 and heralded the beginning of an expanded research effort designed to answer one important question: what is the full therapeutic potential for copper-ATSM as a treatment for MND?

Subsequent research revealed more provocative and exciting observations for the MND scientific community including:

  1. Copper-ATSM is MORE effective in mutant SOD1 mice than riluzole (the only currently approved treatment for MND that is available to MND patients. Riluzole is known to potentially increase survival or time to needing a ventilator by only 3 months))

  2. The benefits of Cu-ATSM in the mutant SOD1 mice are evident even when the treatment starts after the mice have developed overt MND-like symptoms. This means that it can potentially be started at any point in the MND patient’s illness and still have a beneficial effect.

  3. Copper-ATSM is effective when administered orally. This is very important as it means ease of administration and no need for IV infusions or injection of the drug into the spinal fluid.

  4. In a recent follow-up paper in another mouse model, the benefit of Cu-ATSM was especially compelling (http://www.alzforum.org/news/research-news/copper-rescue-als-mice )

Can Cu-ATSM treat the majority of people with MND who don’t have a SOD1 mutation (sporadic MND)?

Unfortunately, there is no perfect animal model for sporadic MND. However, in 2015 Peter Crouch and colleagues at the University of Melbourne and the Florey Institute of Neuroscience presented studies performed on MND-affected tissues obtained from people who died because of sporadic MND. These studies showed important similarities to mice that responded to Cu-ATSM and suggests that Cu-ATSM may have activity in both sporadic and familial MND.

Moving from the laboratory into the clinic

Despite some interesting challenges, the experimental Cu-ATSM molecule has now been developed into a pharmaceutical suitable for human administration. The clinical trial is mow recruiting patients and further details can be found by clicking on this link https://clinicaltrials.gov/ct2/show/NCT02870634

Please note: The Cure for MND Foundation plays no part in determining eligibility criteria of the trials it funds. Please consult with your MND specialist to assess your suitability for trial inclusion.

Lighthouse TrialThe “Lighthouse Trial” is  Phase 2 pilot clinical trial of combination oral anti-retroviral therapy  as a potential treatment option for Motor Neurone Disease (MND) and will start in 2016. Excitement about the possibility of this targeted therapy has grown in recent times due to sound scientific evidence discovery, and recent pre-clinical animal studies.

An overview of the research that has been performed to date, the rationale for why this compound may be an effective treatment, and the status of the clinical trial is briefly summarized below.

A brief history of the research

Despite decades of research, the cause and treatment of MND remains unknown. One of the most interesting theories is that MND may be caused or triggered by a human endogenous retrovirus (HERVs). These viruses infected animals and humans during millions of years of evolution and over time they became part of our genetic makeup (genes). Approximately 8% of human genes have retroviral origins. These HERVs were only discovered around 20 years ago and it is still unknown exactly how they may be related to causing human diseases. However, there is very good evidence that in animals these viruses are associated with a number of neurological conditions. Some preliminary research suggests that one particular retrovirus called HERV K may be linked to MND.

Reviews by Alfahad and Nath (Alfahad T, Nath A. Retroviruses and amyotrophic lateral sclerosis. Antiviral Res. 2013;99(2):180-187) have documented the extensive research on reverse transcriptase activity in MND.

In 2014, Al-Chalabi and colleagues from King’s College described the epidemiology of ALS in terms of a six step cascade of disease progression. They suggested this may be consistent with a sequential triggering process that could be associated with a (retro)viral pathogen.

In early 2016 scientists at the NIH showed that brain samples from MND patients had higher than normal levels of messenger RNA (mRNA) encoded by genes of the human endogenous retrovirus K (HERV-K). A protein encoded by a critical HERV-K gene, called env, was found in brain samples from MND patients but not from healthy individuals. They also showed that activation of HERV-K genes killed healthy human neurons grown in petri dishes. To test the role of HERVs in MND, the scientists genetically modified mice so that their neurons activated the HERV-K env gene. The mice died earlier than normal and had problems with balance and walking that progressively worsened with age, showing similar symptoms to human MND. When the scientists inspected the brains, spinal cords and muscles of these mice they found that only motor neurons, the cells that control movements and die in MND, were damaged. Cells in other parts of the nervous system remained healthy. (Click here for the full article)

Moving from the laboratory into the clinic

This will be the first clinical trial in the world conducted with modern combination anti-retroviral therapy to ameliorate disease progression in patients with MND/ALS.

The study is currently recruiting patients. Clinical trials sites are in Sydney and Melbourne. Detailed inclusion criteria and further information about this trial is available by clicking on the following link https://clinicaltrials.gov/ct2/show/NCT02868580

Please note: The Cure for MND Foundation plays no part in determining eligibility criteria of the trials it funds. Please consult with your MND specialist to assess your suitability for trial inclusion.

Without you MND will keep on killing…. Click to donate today

The Cure for MND Foundation is the largest independent financial supporter of MND research and clinical trials in Australia

We fund the best and brightest MND researchers across Australia to help develop promising new therapies in the lab to the roll into clinical trials for Australians living with MND.

No. of Australian Research Grants Awarded

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$Million Spent on Funding Clinical Trials

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