Boyds has been working with Australian-based biotech company, Actinogen Medical, to develop a novel approach to the treatment of Alzheimer’s disease. Rather than following the traditional treatment paths, it is taking a new route.
This month the first of 174 patients on an international trial will begin taking a drug to lessen the level of the stress hormone, cortisol, in the brain. There is evidence to suggest this hormone plays a role in Alzheimer’s. It is not promoted as the sole cause of the disease but rather as a contributing factor. Current wisdom holds that it is likely that a few factors combine to bring about Alzheimer’s. Some think cortisol may be one of them.
This hormone is released in response to stress, but not the kind of mental stress a stockbroker might experience. Rather it’s the kind experienced when the body is under prolonged challenge from chronic disease, aggressive sport, physical trauma or an event like a heart attack. While reducing the levels of cortisol in the blood is not difficult, reducing it in the brain has, until now, not been possible.
The drug Xanamem, which is being developed in Australia by Actinogen Medical, can do this.
Global significance
With an estimated 50 million* people across the globe living with dementia, finding an effective treatment is becoming a matter of urgency.
There has been an abundance of failures in Alzheimer’s research. In the decade to 2012, the success rate for approved drugs was 0.4 per cent.
The trial aims to use Xanamem, to lower cortisol in the brains of people with early mild Alzheimer’s and assess whether this can delay further deterioration.
“It will be the largest global Alzheimer’s dementia study conducted by an Australian biotech company,” says Dr Bill Ketelbey, CEO and Managing Director of Actinogen.
New therapies are desperately needed and about 100 compounds are presently in clinical research in humans. As no one knows what causes Alzheimer’s, there is no one target.
“Alzheimer’s is one of those diseases where there has to be multiple shots on goals. We’ve got to keep attacking it from every direction because the disease is highly unlikely to have one ultimate therapy, “says Dr Ketelbey. “Rather than a magic bullet, there’s probably going to be a combination of therapies. And the more research we do, and the more failures we have, the better we understand the disease. Failures are crucial to success because they sharpen our focus.”
Much current research is focused mainly on depositions of amyloid plaque and tau in the brain, both of which are hallmarks of the disease.
New target
Cortisol is a new target and Xanamem works differently to any drug in current use.
By last year, the company had completed two phase one trials to assess its safety and how it is handled in healthy people.
The phase two trial XanADu, which has just enrolled the first patient , will assess the safety, tolerability and efficacy of Xanamem for those with mild dementia due to Alzheimer’s.
Double blinded, placebo-controlled and randomised, the trial will follow patients for 12 weeks and be conducted at 20 research sites in Australia, Great Britain and the United States.
Professor Alan Boyd of Boyds has been working with Actinogen Medical to develop Xanemen said, “Cortisol’s potential as a factor in Alzheimer’s was identified at Edinburgh University 15 years ago. As a natural hormone, during the course of a day it goes up and down within normal limits. But the Edinburgh researchers observed that when it was at a high level over a long time, it could be toxic to hippocampus, the part of the brain that assimilates recent memory.
They thought preventing excess production of cortisol in the brain could be useful in treating Alzheimer’s, which is why they developed a substance that worked on an enzyme involved in the production of cortisol and demonstrated it in animal brains. Furthermore, in its phase one trials, Actinogen demonstrated it could work in humans too.”
Promising results
Dr Ketelbey says both animal and human studies have shown raised cortisol is linked to hippocampal shrinkage, neurodegeneration and amyloid build-up.
In animals, he says Alzheimer’s can be induced by raising cortisol to excessive levels in the brain. When the levels are switched down, the Alzheimer’s moderates and may even resolve, with amyloid plaques beginning to decrease.
In January this year, a major independent study funded by CSIRO, yielded compelling data on cortisol. While following a large cohort of well elderly Australians over many years, the researchers looked for bio-markers behind those who developed Alzheimer’s. Two factors stood out: a build-up of beta-amyloid plaques in the brain and raised cortisol in the blood, which provides strong endorsement for the elevated cortisol as a potential target for treating Alzheimer’s disease.
*Alzheimer’s Disease International
