Targeting single enzyme has two-fold effect on Alzheimer’s
Understanding the exact biological mechanisms that give rise to Alzheimer's is still very much an active area of scientific research, but two factors commonly linked to the onset of the disease are inflammation and the accumulation of plaques in the brain. Scientists in Australia have now identified an enzyme that appears to play a role in both, with studies demonstrating that taking it out of the equation can reduce these early biomarkers to regular, healthy levels.
The buildup of plaques like amyloid beta is seen as a key player in the formation of Alzheimer's disease, but the body does have some defensive measures of its own to tackle the problem. The trouble is, as the human immune system fires up in response to these toxic invaders, the immune calls can give rise to an inflammation response that actually compounds the problem.
In new research carried out by scientists at the University of Queensland’s Brain Institute (QBI), an enzyme known as dPI3K has been revealed to have a hand in both processes.
“In nerve cells, the enzyme dPI3K produces a toxic peptide which accumulates into plaques in the brain of Alzheimer’s disease patients, causing havoc,” says Dr Ramón Martínez-Mármol. “Our study shows that the enzyme is also involved in the secretion of one of the most important signaling proteins involved in inflammation.”
Once they’d identified the enzyme as a driver of brain plaque buildup and inflammation, the team began to experiment with ways of stopping it in its tracks. First working with mouse models of Alzheimer's disease, the scientists found that removing the enzyme was an effective way of reducing the plaque and inflammation to healthy levels.
And testing out different drugs that impact dPI3K with a view to human use also produced some encouraging results. The team found one that proved particularly promising, which, conveniently, has already been shown to be safe for human use in cancer treatment. Not-so-conveniently, applying these drugs to diseases of the brain poses another complex problem.
“We found a drug targeting this enzyme had already been used to treat leukaemia – we used it to treat cells taken from mice with the disease and found that the movement of the toxic peptide inside the cells reduced,” said Martínez-Mármol. “The challenge of treating Alzheimer's disease in mice or people rather than isolated cells is that any treatment has to cross the blood-brain barrier.”
The blood-brain barrier is a semi-permeable barrier that separates the cells in the brain from the blood vessels that wind through it. While it plays a vital role in preventing toxic pathogens and the like from entering that all-important organ, it also makes drug delivery a decidedly tricky affair as most won’t make it through, though scientists are making some promising advances in this area. The QBI researchers hope to make yet another.
“We are now keen to collaborate with other researchers to work out how to solve the issue of transporting the drug across the blood-brain barrier,” says Martínez-Mármol.
The study was published in the Journal of Neuroscience, while the video below provides an overview of the research.
Source: University of Queensland