New Compound Shows Potential for Alzheimer’s Treatment

A recently discovered chemical compound is raising hopes for the treatment of Alzheimer’s disease. In trials using a rat model, its effects were notably positive, prompting the biochemists behind it to push forward towards human trials.

One of the key features of Alzheimer’s is the build-up of beta-amyloid plaques in the brain. It remains unclear if these plaques actually cause symptoms or if they are just a byproduct, but they are a central focus for researchers looking for treatments.

Current options for managing Alzheimer’s primarily focus on alleviating symptoms, which makes the search for drugs that target the disease at its core particularly urgent.

Related: Scientists Found 2 Existing Drugs Can Reverse Alzheimer’s Brain Damage in Mice

This new compound operates by removing excess copper from the beta-amyloid plaques.

“About ten years ago, various studies began indicating that copper ions contribute to the aggregation of beta-amyloid plaques,” explains biochemist Giselle Cerchiaro from the Federal University of the ABC (UFABC) in Brazil.

“It was found that genetic mutations and changes in copper transport enzymes can result in copper build-up in the brain, encouraging plaque formation. Therefore, regulating copper levels has become a key strategy for Alzheimer’s treatment.”

Interestingly, not all Alzheimer’s patients have issues with copper: some actually lack sufficient levels of this essential metal. However, for those with an excess, researchers have long thought that normalizing copper levels could alleviate certain symptoms, particularly damage caused by oxidative stress.

The research team evaluated nine different compounds to find the most effective at extracting copper from brain plaques. After preliminary virtual testing, they identified two candidates from the imine group (labelled L09 and L10) and one quinoline-based compound (termed L11) as promising.

These candidates appeared capable of crossing the blood-brain barrier, a crucial requirement for any therapy targeting the brain, and might even be formulated into pills for patients.

Following this, mouse brain cells were subjected to each compound for a full day to assess their toxicity. L11 turned out to be the most harmful, showing evidence of increasing oxidative stress, which is not ideal.

On the other hand, L09 and L10 showed lower toxicity levels and were effective at protecting the cells’ lipids and DNA from damage usually linked to beta-amyloid presence.

With these findings, the team then moved on to testing in live models by injecting rats with streptozotocin, which destroyed insulin-making beta cells and led to beta-amyloid clumping in their brains.

In these tests, compound L10 stood out as a top candidate for future human clinical trials. It helped restore copper balance in the hippocampus, a critical area for memory, while also reducing neuroinflammation and oxidative stress. Rats treated with L10 performed significantly better in maze tasks designed to assess spatial memory than those given other compounds.

In contrast, L09 and L11 showed much less efficacy across the board.

Cerchiaro and her team are enthusiastic about moving forward with human clinical tests, which will provide better insight into how effective this treatment may be for the estimated 55 million people living with Alzheimer’s worldwide.

“It’s a remarkably simple, safe, and effective molecule,” Cerchiaro remarks. “Our compound is much more affordable than existing medications. Even if it only helps some patients, considering Alzheimer’s has various causes, it would be a significant step forward compared to current treatments.”

This research is documented in ACS Chemical Neuroscience.