A toxic protein called amyloid beta is thought to play a key role in the onset of Alzheimer’s disease (AD). In healthy people, amyloid beta is degraded by enzymes as it forms. However, in patients with AD, these enzymes appear unable to adequately perform their actions, causing the toxic protein to accumulate into plaque deposits, which many researchers believe leads to dementia.
One of the Holy Grails of the pharmaceutical industry has been to find a drug that stimulates these enzymes in people, particularly those who are in the early stages of dementia, when amyloid plaques are starting to accumulate.
Researchers at Monash University in Australia believe they have discovered this elusive drug candidate––a molecule in snake venom that appears to activate two enzymes (neprilysin and endothelin-converting enzyme-1 [ECE-1]) involved in breaking down the amyloid plaques in the brain that are the hallmark of AD.
Dr. Sanjaya Kuruppu and Professor Ian Smith at the university’s Biomedicine Discovery Institute published their research in Nature Scientific Reports.
Kuruppu has devoted his career to studying snake venom, looking for drug candidates. When he began researching AD, “snake venom was an obvious place for me to start,” he says.
He was looking for a molecule that would stimulate the brain’s enzymes to break down amyloid plaques. What he found, when screening various snake venoms, was a peptide (K49-P1-20) with the ability to enhance the activity of neprilysin and ECE-1. The molecule was extracted from the venom of Bothrops asper, a pit viper found in South and Central America.
Kuruppu and his team have developed synthetic versions of the molecule. Initial tests performed in the laboratory using human cells have shown that it has the same effects as the native version found in snake venom.