Pioneering new treatments for dementia and addiction recovery
Clinical trials are underway to test a promising new treatment for dementia which could also help people recovering from addiction. Professor Michael Bowen talks about his journey from the lab to company co-founder on his mission to help people struggling with “forgotten disorders”.
When people think of dementia, it’s often the memory and cognitive challenges that come to mind. But major behavioural and psychological changes also occur. Perhaps the most devastating of these are agitation and aggression. As many as 76 percent of people with dementia experience symptoms of agitation and aggression and it is these symptoms that are the major driver of people having to move into nursing homes or specialised care facilities.
Kay Morrison is a dementia advocate who lives on the NSW north coast. Her husband, Ross, experienced dementia as a result of his Alzheimer’s disease. Ross would often experience the common ‘sundowning’ phenomenon, Kay says, which is where people living with dementia can become increasingly agitated from the late afternoon and into the night.
“I was Ross’ primary carer for seven years before he passed away last year. Every career experiencing aggression from their loved one would agree there needs to be a better way to manage that aggression and take their fear,” says Kay.
A new treatment first developed at the University of Sydney could be the solution.
Kinoxis Therapeutics was founded on the basis of the research led by scientists at the University of Sydney. Kinoxis is taking a newly developed molecule, KNX100, from the lab into clinical trials and eventually to market. Professor Michael Bowen, Co-Founder and Chief Scientific Officer of Kinoxis, says it’s an exciting time for the team.
“Kinoxis launched its first Phase 2 clinical trial in the second half of last year,” Professor Bowen says, “which is being run at multiple sites across Australia to test the ability of this new substance to treat agitation and aggression in dementia. This is a major step forward in the development of this potential new treatment.”
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The only drugs currently approved to treat agitation in dementia at present are atypical antipsychotics.
Two of the major issues with these current treatments are they are sedating and have significant cardiovascular risks. These issues result in atypical antipsychotics carrying a fourfold increased risk of death in elderly patients with dementia.
“Based on our preclinical and Phase 1 clinical trial data, our new medication has the potential to treat agitation and aggression without this sedation or increased risk of death,” says Professor Bowen.
“Clearly we need better options.”
For Kay, sedatives did help to manage Ross’ symptoms but they’re not as effective for everyone.
Kay says carers also don’t want to see their loved ones permanently medicated to the point they’re not themselves anymore, as was common in the nursing home Ross was placed in towards the end of his life.
“Ross would start to get agitated every evening, and our only option was to use Memantine – a mood stabiliser – every afternoon to settle him down,” Kay says. “He was a big guy – strong and with a powerful voice. He wouldn’t know it was me, or our children, that he was being aggressive to.
“Some people also refuse to take the sedatives because they don’t like how it makes them feel. Trying to persuade them otherwise would only make them more agitated.”
Professor Michael Bowen in the lab. Photo: University of Sydney / Stefanie Zingsheim
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LinkTo get a new drug to market costs about double the combined budget of all four Marvel Avengers movies combined; if you can’t make a commercial case for your solution you’re probably not going to get anywhere
Kinoxis’ medication works in a completely new and different way to existing drugs, targeting an enzyme within cells that we know is increased in the brains of people with dementia. This enables it to normalise activity in circuits in the brain that drive agitation and aggression.
Professor Bowen says that Kinoxis’ medication has also shown promise in pre-clinical studies of addiction, which could also make it a powerful tool for treating various substance use disorders, including alcohol, opioid and methamphetamine use disorders.
Professor Bowen has worked for over 15 years researching KNX100 and systems in the brain that might provide new targets for treating psychiatric and neurological disorders. In that time, he’s had his moments of doubt: Will this work? What will happen if we can’t come up with the solution these people need?
“Ultimately, what keeps me going is I truly believe in what we’re doing,” he says. “I believe in the quality of the science, in the capabilities of the incredible team I have the privilege of working with, and above all, in the potential of the technologies we’re developing to make a real difference for those with dementia or substance abuse disorders.”
Research at the University of Sydney's Brain and Mind Centre extends beyond the lab into clinics and partnerships with industry. Photo: University of Sydney / Louise Cooper
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LinkProfessor Bowen recalls that he didn’t always feel the calling to become a psychopharmacologist.
“I think I must have fancied myself a bit of a fledgling Renaissance man during my school years. I read broadly and deeply and had many interests, including the brain, but it wasn’t until I reached university that I really started to home in on neuroscience and psychopharmacology.”
The more he learned, the more it became apparent that there are many disorders of the brain and mind that have a devastating impact on huge numbers of people around the world. And yet, for many of these disorders, there are no or few treatments – the ones that are available don’t work for many, and there is very little in the development pipeline.
“I often call these the ‘forgotten disorders’,” Professor Bowen says.
“Seeing people very dear to me struggle with these challenges made the issue hit home on a personal level. It was this combination of my studies and my personal experiences during my undergraduate years that galvanised me to focus on developing new treatments for disorders of the brain and mind.”
Part of the reason why there are so few effective treatments, and little in the works, is the difficulty in turning findings from the lab into impact.
“Perhaps naively, I used to think the science drove everything,” he says, “that if you had good science, everything else would more or less fall into place, and you’d be able to navigate a relatively straight path to the patients you’re trying to help.”
What he learnt very quickly while working on KNX100 is that a lot of stars need to align to develop new treatments.
“To get a new drug to market costs about double the combined budget of all four Marvel Avengers movies combined; if you can’t make a commercial case for your solution you’re probably not going to get anywhere.”
Scientists also have to convince the clinicians who will administer the drug if it does make it to market so it can actually reach the patients who need it. Then there are the regulators. You not only have to convince them that your drug is safe, but also come up with a way of demonstrating it works that they’ll accept.
“That isn’t always straightforward when you’re working on something truly novel.”
Professor Bowen was part of the Sydney Ideas talk 'Medical Moonshots', on fast-tracking cures for diseases. Now available on-demand. (L-R) Antoine van Oijen, Chenyu Tim Wang, Victoria Cogger, Tegan Taylor, Michael Bowen. Photo: University of Sydney / Michael Amendolia
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LinkIn my work with Dementia Australia and speaking to other families while caring for Ross, I can see what a positive impact a new treatment for aggression would have.
With the launch of its Phase 2 clinical trial, Kinoxis has made it a lot further than most research spinouts typically do.
Next on the horizon for Kinoxis is the launch of three separate phase 2 trials of its medication in addiction – spanning alcohol, opioid and methamphetamine use disorders.
“We’re also further developing some really exciting preclinical stage technologies that I hope will progress into the clinic over the coming years,” Professor Bowen says.
For carers like Kay, the progress can’t come soon enough.
“In my work with Dementia Australia and speaking to other families while caring for Ross, I can see what a positive impact a new treatment for aggression would have. This could really improve the quality of life for people with dementia and make caring for them a lot safer and easier.”
Professor Michael Bowen is a neuroscientist and psychopharmacologist at the University of Sydney’s Brain and Mind Centre and School of Psychology.
This article was produced with the support of Dementia Australia, the peak organisation for dementia in Australia.
Declaration
The University of Sydney is a shareholder in Kinoxis Therapeutics. Researchers Professor Michael Bowen and Professor Michael Kassiou are participants in the Kinoxis Therapeutics Employee Share Option Plan.