London – Scientists have broken new ground in the search for an Alzheimer’s cure by discovering a potential cause of the disease, which could be targeted with drug treatments.
In findings that experts said could “open new doors” in the increasingly frustrated global hunt for a therapy for dementia, US researchers announced that studies of Alzheimer’s in mice had thrown up a new process that they believe contributes to the disease’s development.
The team at Duke University in North Carolina observed that with Alzheimer’s, immune cells that normally protect the brain instead begin to consume a vital nutrient called arginine.
By blocking this process with a drug, they were able to prevent the formation of “plaques” in the brain that are characteristic of Alzheimer’s disease, and also halted memory loss in the mice.
While no technique that is tested in an animal can be guaranteed to work the same way in humans, the findings are particularly encouraging because, until now, the exact roles of the immune system and arginine in Alzheimer’s were completely unknown.
The discovery was welcomed by experts in the UK, who said it had filled in gaps in our understanding of Alzheimer’s and could pave the way for future treatments for the devastating condition, which affects more than 500,000 people in the UK alone.
The drug that was used to block the body’s immune response to arginine - known as difluoromethylornithine (DFMO) – is already being investigated in pharmaceutical trials for certain types of cancer and may be suitable for testing as a potential Alzheimer’s therapy.
A new drug target for the disease would be hugely welcome in a field where funding and industry’s will to invest have been waning, in spite of the growing human and economic cost of Alzheimer’s and other forms of dementia.
The number of people worldwide living with some form of dementia is set to reach 135 million by 2050. However, after a string of costly failures to bring effective drugs to market, pharmaceutical companies are increasingly cutting funding for research.
The G8 nations pledged in 2013 to find a major new dementia treatment or cure by 2025, and the Coalition committed the UK to doubling its contribution toward this goal to £132m by that date.
Carol Colton, professor of neurology at Duke University, and senior author of the new study, said research had been dominated by an attempt to understand the role of amyloid – the protein that builds up in the brain to form plaques – but that a focus on arginine and the immune system could yield new discoveries.
“We see this study opening the doors to thinking about Alzheimer’s in a completely different way, to break the stalemate of ideas in Alzheimer’s disease,” she said.
“The field has been driven by amyloid for the past 15, 20 years and we have to look at other things because we still do not understand the mechanism of disease or how to develop effective therapeutics.”
Arginine is an amino acid and an essential nutrient for several bodily processes, including cell division, healing and immune responses.
It is found in food, including dairy products, meat, nuts and chickpeas, but the team at Duke said their study did not suggest eating more arginine would have an impact on Alzheimer’s risk.
The blood-brain barrier regulates how much arginine can enter the brain, and the immune response that breaks down arginine would stay the same even if confronted with higher levels of the nutrient.
Their study, which is published in the Journal of Neuroscience, was led by Matthew Kan, an MD/PhD student in Professor Colton’s lab.
Dr Laura Phipps, from Alzheimer’s Research UK, said it was important for human tests to confirm the findings.
“Clinical trials are essential before any potential new treatment can be given to people, but these early findings could open new doors for future treatment development for Alzheimer’s,” she said.
“The study suggests that low levels of arginine in the brain could contribute to the death of nerve cells in Alzheimer’s, but there is much more we still need to understand about how and why nerve cells die in the disease,” she added.
Dr James Pickett, head of research at the Alzheimer’s Society, said the new study “joins some of the dots in our incomplete understanding of the processes that cause Alzheimer’s disease”.
“Importantly, these new findings reflect earlier observations that arginine is reduced in the brains of people with Alzheimer’s disease,” he said. “The next step would be to show that targeting arginine metabolism in the brain can reduce the death of brain cells, as this was not shown in the current study.”
Alzheimer’s is the most common form of dementia and affects around 500,000 people in the UK. The number of people living with dementia is set to rise to above one million within 10 years, with huge costs to families, the NHS and social care services.
Dementia Cure Search; Failure and Sucesss
Drugs: Some of the biggest drug companies have invested hundreds of millions of dollars seeking a viable treatment. A major blow came in 2012, when Pfizer reported that its drug Dimebon had shown no benefit in trials, costing the company $750m. Unsuccessful trials of two other drugs followed in the same year.
Halting brain cell death: The fundamental cause of mental decline in Alzheimer’s is brain cell death. In 2013, researchers at the University of Leicester halted the process in mice with a drug – a breakthrough which one expert said would be judged by history as a “turning point”. Further studies are ongoing.
Ultrasound: A new technique pioneered in Australia this year uses ultrasound waves to break down plaques in the brain. In mice, this led to improvements in memory, but there are concerns that the complexity of the human brain could mean its functioning might be damaged.
The Independent