Scientists unlock secrets of drugs used to treat Alzheimer’s

The scientists have also uncovered a molecular explanation for early-onset hereditary forms of Alzheimers which can strike as early as 30 years of age

Research has found how two classes of drug compounds worked to fight the disease in clinical trials.

The experts’ research suggests that these compounds target disease-causing peptides with “high precision” and with minimal side-effects.

The scientists have also uncovered a molecular explanation for early-onset hereditary forms of Alzheimer’s which can strike as early as 30 years of age.

The conclusions of their research, published in the journal Nature Communications, were described yesterday as “tremendously encouraging” regarding the future of therapies that could keep Alzheimer’s in check.

Alzheimer’s is characterised by a build up of small biological molecules, known as amyloid peptides, produced by all of us, but in disease victims these peptides collect in the brain into toxic plaques – called amyloid plaques – that destroy the surrounding neurons and affect the mind.

The process starts with a long protein, called APP, which is located across the neuron’s membrane. For reasons not yet fully understood, APP protein can be cut in several different places, producing amyloid peptides of varying lengths. Only the longer forms of the amyloid peptide carry the risk of aggregating into plaques, and people with Alzheimer’s produce an abnormally high number.

The two next-generation drugs currently in clinical trials target an enzyme that cuts APP, known as gamma secretase.

Until now, understanding of the mechanism involved has been lacking. However, the latest research has been able to shed some more light on it by determining how the drug compounds work on the plaques.

Compared to previous therapeutic efforts, this is considerable progress, the scientists said.

Earlier clinical trials had to be abandoned in 2010 because the compound being tested resulted in side-effects including internal bleeding and skin cancer.

Senior research author Dr Patrick Fraering, of EPFL in Switzerland, said: “Scientists have been trying to target gamma secretase to treat Alzheimer’s for over a decade.

“Our work suggests that next-generation molecules, by modulating rather than inhibiting the enzyme, could have few, if any, side-effects. It is tremendously encouraging.”

During their investigation, the scientists also identified possible causes behind some hereditary forms of Alzheimer’s.

Co-author of the research findings Dirk Beher said: “We have obtained extraordinary knowledge about how gamma secretase can be modulated. This knowledge will be invaluable for developing even better targeted drugs to fight the disease.”