In the burgeoning field of Alzheimer’s research, many drugs are currently in development with the intent to delay, slow, or reverse symptoms of the disease. However, some are generating significant buzz.

This week, England’s health spending watchdog made headlines again by rejecting a new Alzheimer’s medication, marking the second time this year such a decision has occurred. Both donanemab and lecanemab received approvals from the UK’s Medicines and Healthcare products Regulatory Agency (MHRA). Nonetheless, the National Institute for Health and Care Excellence (NICE) deemed their benefits insufficient to warrant their costs, coupled with concerns about potential side effects including brain swelling and bleeding.

For experts like Professor Rob Howard from University College London, this decision highlights the urgent need to ensure that individuals with Alzheimer’s have access to timely diagnoses, therapy, social care, and existing treatments that can alleviate symptoms.

While many share Howard’s perspective on the importance of current support systems, there is also a sense of optimism about the potential role of disease-modifying drugs. Alzheimer’s Research UK reports that approximately 130 drugs are currently in development, with three-quarters aiming to alter the course of the disease.

“Many promising treatments are in the pipeline,” says Professor Tara Spires-Jones, a neurodegeneration expert at the University of Edinburgh.

Let’s delve into some of these promising treatments:

**Amyloid-Beta Targeting Drugs**
Amyloid beta, a sticky protein, is a defining characteristic of Alzheimer’s disease, leading to disrupted cell communication and inflammation. Monoclonal antibodies like lecanemab and donanemab target and prevent the accumulation of these troublesome clumps.

Despite NICE’s recent decisions, some believe there is still hope for these drugs. Professor Andrew Doig, from the University of Manchester, remarked, “Donanemab hasn’t been entirely ruled out; circumstances could change in the future. We will continue to monitor its long-term efficacy, and costs might decrease as well.”

Dr. Rich Oakley, Associate Director of Research and Innovation at Alzheimer’s Society, pointed to another hopeful candidate: the monoclonal antibody remternetug. “This drug targets amyloid just like donanemab, but it is anticipated to be more effective, practical, and have fewer adverse effects,” he explained.

Another intriguing development is buntanetap, a small molecule designed to reduce the production of toxic amyloid precursors. Oakley noted, “Recent trials showed significant improvements in memory and cognitive functions after just 12 weeks of treatment, without any serious side effects.”

Additionally, valiltramiprosate, an oral medication, is under investigation for individuals carrying a gene that increases their Alzheimer’s risk.

**Innovative Approaches**
Professor Charles Marshall from Queen Mary University of London mentioned another intriguing avenue: altering the timing or manner of amyloid-lowering treatments for better efficacy. “Trontinemab is a revamped version of a previously tested amyloid-lowering molecule that can more easily penetrate the brain. This might allow for greater impacts on amyloid proteins at lower doses, which could minimize side effects,” he explained.

**Tau-Lowering Drugs**
Notably, buntanetap not only decreases beta-amyloid but also reduces tau levels in the blood, and it isn’t alone in this regard. Marshall highlighted BIIB080, or MAPTRx, which works by “turning off” the gene responsible for producing tau protein. Although still in early stages, there are hopes this medication could slow the physical progression of Alzheimer’s symptoms.

**Inflammation and New Treatments**
Among the drugs stirring excitement are liraglutide and semaglutide, commonly known for their use in weight-loss injections. These drugs may help slow Alzheimer’s progression by reducing brain inflammation. Preliminary data suggests liraglutide can reduce brain shrinkage and slow cognitive decline.

Multiple phase 3 clinical trials are currently exploring potential benefits of semaglutide for Alzheimer’s patients. However, experts caution that the future of treatment will likely not rely on a single solution. Marshall noted, “For amyloid-lowering treatments to be more effective, they might need to be used in conjunction with therapies targeting other aspects of Alzheimer’s like tau protein or inflammation.”