U of A team takes step toward an Alzheimer’s drug
Medical researchers find compound that may help fight the degenerative disease
What we hope is to advance the research far enough that it becomes an attractive drug target for Big Pharma to invest in.
A team of University of Alberta medical researchers examining Alzheimer’s disease has completed a new study that could lead to the development of a powerful pharmaceutical weapon against the degenerative illness.
Testing on genetically engineered mice found that a particular compound known as AC253 has a significant beneficial impact against a rogue protein associated with Alzheimer’s.
“Not only did we find that the amyloid burden in the brain was reduced … but also, importantly, the mice didn’t demonstrate any side effects like weight gain or loss,” said team leader Dr. Jack Jhamandas. “So this is very interesting and exciting.”
Alzheimer’s, which currently afflicts more than 500,000 Canadians, has presented a frustrating puzzle for scientists trying to figure how it develops and how it can be stopped.
To date, a large swath of research has looked at the behaviour of abnormally deposited proteins, such as the amyloid protein, which are found in large volumes in the brains of patients with the disease.
Jhamandas said his team’s re- search is based around the fact that amyloids produce their toxic effect by interacting with specific types of receptors, including one known as the amylin receptor.
This is where AC253 comes in. The compound, which was actually developed for diabetes, blocks the amylin receptor. Previous research from Jhamandas’ team showed the drug can protect individual nerve cells that have been exposed to amyloid proteins.
For the new study, his team took the research from the petri dish to animal testing, specifically mice that were genetically engineered to develop Alzheimer’s.
“When these mice are born, they are normal, but by six months their brains are riddled by amyloid plaques and they cannot find their way out of the proverbial paper bag,” Jhamandas said.
In the first part of the study, mice were injected with AC253 directly into the brain. After five months of treatment, the mice performed significantly better in tests of memory and learning than a group of mice that didn’t receive the drug, Jhamandas said.
The problem is that injecting a drug directly into the brain is not a practical approach for humans, so the U of A team also looked at a different delivery method.
Team member Dr. Raina Soudy modified the AC253 compound from a long string of amino acids into a new, round shape, which provided better stability in the blood and had an easier time entering the brain.
For the second part of the study, mice were injected in their bellies with this modified, round form of the compound. The results were similar, with the team noticing fewer amyloid plaques and reduced markers of brain inflammation.
The group is now chopping up AC253 — coincidentally the same number as a daily Air Canada flight between Edmonton and Vancouver — into small pieces.
Such fragments are more stable and are an easier tool for making a drug in pill form.
“To make a pill, that’s the end game,” Jhamandas said. “What we hope is to advance the research far enough that it becomes an attractive drug target for Big Pharma to invest in and develop the drug for Alzheimer’s.”