What are the most promising Alzheimer’s disease-modifying drugs?

This week, England’s health funding agency rejected a new Alzheimer’s drug – the second drug it has rejected this year.

Both donanemab and lecanemab have been approved by the UK’s Medicines and Healthcare Regulatory Agency (MHRA), however the National Institute for Health and Care Excellence (Nice) said their benefits were too small to justify their cost, while there have been concerns about their availability. side effects – such as swelling of the brain and bleeding.

For others, including Professor Rob Howard of University College London, the decision highlights the importance of focusing on ensuring people with Alzheimer’s disease have access to diagnosis, treatment, social care and medicines. there can help the symptoms of this disease.

But while others believe that such support is important, they are hopeful that disease-modifying drugs can play a role. According to Alzheimer’s Research UK, around 130 drugs are being developed, three of which aim to delay, delay or reverse the disease.

“There are many promising treatments coming through the pipeline,” said Professor Tara Spires-Jones, a neurodegeneration expert at the University of Edinburgh.

Here’s a look at some of those treatments:

Amyloid-beta drug targeting

Accumulation of an adhesive protein known as amyloid beta is a hallmark of Alzheimer’s disease, which causes disruption of cell communication, inflammation and cell death. Lecanemab and donanemab, both monoclonal antibodies, prevent these clumps from forming.

Some believe that the Nice decisions are far from the end of these drugs. Professor Andrew Doig, from the University of Manchester, said: “Donanemab has not been ruled out forever and this decision could change. We will continue to monitor how well it works in the long term. Costs too they can go down.”

Other drugs are also on the way and may work better than donanemab, Doig added.

Dr Rich Oakley, deputy director of research and innovation at the Alzheimer’s Society, said one such drug is the monoclonal antibody remternetug. “It targets the same type of amyloid as donanemab but it is hoped to be more effective, more effective and reduce the side effects seen with other immunotherapy drugs,” he said.

Another drug of interest is buntanetap – a small molecule that helps reduce the production of amyloid toxic precursors. “A recent trial showed a significant improvement in memory and reasoning in people with early Alzheimer’s disease during 12 weeks of buntanetap treatment,” said Oakley. “Importantly, buntanetap treatment did not cause serious side effects.”

There’s also valiltramiprosate, an oral drug that’s being looked at for people with genes that put them at risk of developing Alzheimer’s disease.

Professor Charles Marshall of Queen Mary University of London said one way is to change the setting in which the amyloid-lowering treatment is given, or the way it is administered, to make it more effective.

He said: “For example, trontinemab is a new type of amyloid-busting molecule that has been tested and has been modified to get into the brain more easily. This means that it can have a significant effect on the amyloid protein in the brain even when given in a low dose that may have minimal effects. ”

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after the news release

Tau lowering drugs

Buntanetap not only lowers beta-amyloid levels but, as Oakley points out, has also been found to reduce tau levels in the blood. And it’s not the only drug that affects this protein.

Marshall also says that BIIB080, or MAPTRx, is causing enthusiasm. This works by “turning off” the gene that produces the tau protein. While it is still early days, experts now hope to test whether the drug can slow the progression of the physical symptoms of Alzheimer’s.

Swelling

Among the drugs causing a stir in this area are liraglutide and semaglutide – perhaps best known for their use in weight loss.

There are several ways these drugs can help slow Alzheimer’s, including reducing levels of inflammation in the brain. Early data are promising, and liraglutide has been found to slow down degeneration in parts of the brain and slow down the aging process.

A number of 3 clinical trials are ongoing to evaluate whether semaglutide has benefits in people with Alzheimer’s disease. However, with many drugs in development, and targeting different targets, experts say the long-term goal is impossible to include in one type of treatment.

“It’s also possible that for treatments that lower amyloid to be more effective, we need to give them in combination with treatments that target other components of Alzheimer’s disease such as tau protein or inflammation,” Marshall said. brain.”