An Alzheimer's drug has shown promise in animals.
The memory-robbing disease has no cure, with treatments aiming to temporarily ease symptoms.
Alzheimer's is thought to come about when proteins build-up in and around brain cells, leading to abnormal plaques and tangles.
Scientists have previously tried to inhibit a key enzyme involved in the plaques' formation, leading to serious side effects.
A team from the University of California San Diego has therefore developed a drug that alters the extent of the enzyme's activity.
When tested on macaques, the drug candidate reduced the primate's amyloid-β 42 levels by up to 70%. Amyloid-β 42 is a protein fragment that is particularly prone to forming Alzheimer's-related plaques.
The scientists are awaiting approval from the US Food and Drug Administration to test the drug's safety in healthy volunteers.
They hope the medication may one day be used to prevent Alzheimer's in at-risk people, similar to how statins are prescribed to ward off heart disease in those with high cholesterol.
More than 850,000 people had dementia in the UK in 2019, with Alzheimer's affecting 50% to 75% of these patients. In the US, over 6 million people have Alzheimer's.
Alzheimer's-related plaques, composed of the protein amyloid, form around brain cells. Amyloid is a normally-occurring protein, however, it accumulates in Alzheimer's patients.
Amyloid is made up of smaller protein fragments known as amyloid-β peptides.
These peptides are generated via the enzymes β-secretase and γ-secretase when they split another protein on the surface of nerve cells to release amyloid-β fragments, like amyloid-β 42.
Amyloid-β 42 is elevated in patients with mutations that predispose them to early-onset Alzheimer's.
Drug candidates have previously worked to inhibit β-secretase and γ-secretase. This was unsafe, however, likely due to the enzymes being required to split additional proteins in the brain and other organs.
So-called γ-secretase modulators (GSMs) may be a better approach, with these medications altering the enzyme's activity so it produces fewer of the amyloid-β peptides that are prone to forming plaques, but still splits other proteins as required.
"GSMs therefore offer the ability to mitigate mechanism-based toxicities associated with γ-secretase inhibitors," said study author Professor Steven Wagner.
Watch: Depression and anxiety linked to Alzheimer's
The scientists found their GSM candidate reduced amyloid-β 42 levels by up to 70% in macaques.
Repeated low doses of the drug also eliminated amyloid-β 42 production in mice and rats, with no serious side effects.
The scientists then tested their GSM drug in mice with early-onset Alzheimer's, either before or shortly after the rodents formed amyloid plaques.
In both cases, the medication reduced plaque formation and its associated inflammation, which is thought to exacerbate Alzheimer's development.
The results, published in the Journal of Experimental Medicine, suggest GSMs could be used as a preventative treatment in patients with genetic mutations that make them more susceptible to Alzheimer's or in those with detectable amyloid plaques on their brain scans.
"In this study, we have pharmacologically characterised a potent GSM that, based on its preclinical attributes, appears to equal or exceed the potency of any previously tested GSMs," said co-author Professor Rudolph Tanzi, from Massachusetts General Hospital.
"Future clinical trials will determine whether this promising GSM is safe in humans and could be used to effectively treat or prevent Alzheimer's disease."
The scientists hope to initiate a phase 1 clinical trial in around 100 human volunteers at some point in 2021.
"It would be a typical single and multiple ascending dose in healthy individuals," Professor Tanzi told SWNS.
"If we get through phase 1, phase 2A would be in Alzheimer's patients and [would] include looking at biomarkers for reducing beta-amyloid in the brain."
If sufficiently safe and effective, the drug could be used as a preventative treatment.
"Just like we have to lower cholesterol levels early in life, for decades, to avoid heart disease later in life, we will need to lower brain beta-amyloid levels early in life, for decades to reduce risk for Alzheimer's," said Professor Tanzi.
"This means the drug we use to do that must be safe, inexpensive and easy to administer; for example, a small molecule pill."
The scientists believe "tens of millions" of people in the US alone could benefit from "controlling amyloid-β accumulation in the brain".
"We hope our gamma secretase modulator will someday be able to do just that," said Professor Tanzi.
Watch: Controlling blood pressure may help prevent Alzheimer's