Research into Alzheimer’s enters crucial phase, as clinical trial results presented at major conference

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By Quang Tran | Tuesday 02 August 2022

  • Updates from clinical trials presented at world’s largest dementia research conference
  • Diverse treatment pipeline, drug and non-drug approaches discussed including crezanumab, butantetap, T3D-959, and exercise
  • Alzheimer’s Research UK urging government and NHS to get ahead of the curve in preparation for new treatments

Research presented today (Monday 1 August) at the 2022 Alzheimer’s Association International Conference (AAIC) in San Diego gives an overview of clinical trial results for potential drugs for the diseases that cause dementia, as well as top line results on the impact of exercise on cognition in mild cognitive impairment.

Our expert comment

Speaking about new drug treatments, Dr Rosa Sancho, from Alzheimer’s Research UK, said:

“Dementia research is at a crucial phase, particularly in the search for life-changing treatments for people with the disease. Many years of funding pioneering research, backing bright people with bold ideas, has taken us to this point, with several potential Alzheimer’s treatments on the horizon.

“But while there are now nearly 150 drugs in clinical trials for Alzheimer’s’ disease, the reality is that, even if any one of these new drugs were to be deemed safe and effective for use in the UK, most people with dementia in this country would still face a significant wait to access them.

“We need to see urgency from political leaders and the NHS to ensure our health system is ready for a breakthrough in Alzheimer’s treatment that we all hope is imminent. And we hope that the Government’s forthcoming Dementia Strategy sets out a clear and urgent roadmap for action.”

Detailed results for anti-amyloid drug crenezumab discussed

The pharmaceutical company Roche has previously announced that its potential Alzheimer’s drug, crenezumab, did not slow or prevent cognitive decline in people with a specific genetic mutation which causes early-onset Alzheimer’s disease. The drug is designed to target and eradicate a protein called amyloid from the brain. Amyloid build-up is a hallmark of Alzheimer’s disease.

At AAIC, researchers from the US will give a more detailed breakdown of these results, discussing the impact of the drug in study volunteers, and the impact on markers of disease.

The trial looked at the effect of the drug on people who carry faults in a gene called PSEN1, which are the most common cause of inherited forms of Alzheimer’s disease.

Speaking about the presentation, Dr Rosa Sancho, Head of Research at Alzheimer’s Research UK, said:
“While it’s disappointing to see any potential Alzheimer’s drug end without making a meaningful difference to people’s memory and thinking, full study results like these can still provide important insights that could shape future drug trials.

“The amyloid protein remains a key player in Alzheimer’s disease and while a number of ongoing trials are investigating drugs that target this protein, it’s also important to widen the number of approaches being explored to treat the disease.

“The unique group of participants in this trial allowed researchers to test Alzheimer’s drugs before they started to show symptoms. While testing before symptoms show is thought to be important for giving new drugs the best chance of success, this isn’t the only factor that matters, and strong genetic drivers may have played a part here. We expect to see trial results of three more anti-amyloid drugs in the coming months – these drugs target larger clumps of amyloid than the smaller clusters of protein targeted by crenezumab. Many researchers believe these play a more important role in Alzheimer’s, so we’re keen to see results of these other trials.”

Buntanetap shows improved thinking in small Alzheimer’s trial, and positive signs larger trial for Parkinson’s disease

Many potential dementia drugs are designed to clear away protein fragments that stick together and build up into clumps in the brain. Buntanetap (previously known as posiphen) has a different mechanism of action – it aims to limit the production of proteins that cause the sticky fragments in the first place.

Preliminary studies have shown that it can reduce levels of four brain proteins, including the hallmark Parkinson’s protein, alpha-synuclein; and the precursor to the hallmark Alzheimer’s protein, amyloid. This has led to a number of clinical trials, results of which will be presented today at AAIC.

In a small (Phase 2) trial of people with Alzheimer’s disease, volunteers received either 80mg of the drug or a dummy drug (placebo). Ten people received the drug and five people had the placebo.

Researchers from the pharmaceutical company, Annovis Bio looked at markers of Alzheimer’s disease, and found those who received the drug were more likely to have improved nerve structure and function, and lower levels of inflammation.

The researchers also looked at the effect on thinking skills in study volunteers, with results suggesting they improved after 25 days of treatment.

Researchers from Annovis Bio also shared results from a Phase 2 trial looking at the effects of people with Parkinson’s disease. In this research they looked at five different doses of the drug and tested them against a placebo.

Researchers found the 10mg and 20mg doses improved people’s mobility the most. This data supported the FDA’s decision to award a phase 3 trial for Parkinson’s disease.

Dr Rosa Sancho, at Alzheimer’s Research UK, said:
“These findings need to be interpreted with caution as research investigating this drug in people with Alzheimer’s disease is at an early stage, with only a few people receiving the drug. The researchers are planning further short term and longer-term clinical trials to find out more about any clinical benefits of the drug in people living with Alzheimer’s, and we hope these build on the early promise shown in the data presented today.

“While there are many differences between neurodegenerative diseases, there are also commonalities, so it’s encouraging to see the same drug in clinical trials for Alzheimer’s and Parkinson’s disease.”

Safety data to be presented for T3D-959 – a drug that targets brain glucose

Researchers from the US will present results from trials of an experimental drug that targets impaired glucose and lipid metabolism, both of which are impaired in Alzheimer’s disease.

The drug called T3D-959 acts to overcome insulin resistance, maintain brain metabolism and keep the brain functioning well.

The drug is designed to be taken orally once-a-day for 24-weeks, and researchers are investigating three different doses of the drug – 15g, 30mg, 45mg – and comparing against a placebo.

In a phase 2a trial, researchers will look to see whether the drug improves people’s memory and thinking.

They will also look at other measures including markers of disease in the blood and spinal fluid.

The ongoing trial, called PIONEER, started in March 2021 and is looking at over 250 people with mild to moderate Alzheimer’s disease.

Head of Research, Dr Rosa Sancho, said:
“Alzheimer’s is a complex disease involving changes in several different biological processes. A growing body of evidence points to the important role of glucose – the fuel that cells in the body and brain typically use to function and survive. Improving the way our brain cells use energy is a promising strategy for slowing the effects of diseases like Alzheimer’s.

“Like any new drug, T3D-959 will need to go through a series of clinical trials in people and this approach is a long way off being proved successful in humans. Results of this Phase 2 trial aren’t expected to be seen till next year, so we will have to wait for more details.”

Impact of exercise in people with mild memory problems – top line results from the EXERT trial

In another study presented at AAIC, researchers in the US looked at the impact of exercise on memory and thinking in people with Mild Cognitive Impairment (MCI).

Participants were split into two groups: one which did stretching and balancing activities, and another which did aerobic intensity training over the course of the study.

For the first 12 months of the study, participants carried out exercise twice a week under supervision and completed unsupervised exercise a further two times a week. Between months 13-18 all their exercise was unsupervised.

There was no decline in memory and thinking in either group over the course of the study.

However, compared with people in separate studies, who didn’t carry out an exercise regime, participants performed better on memory and thinking tests after 18 months.

Dr Rosa Sancho, Head of Research at Alzheimer’s Research UK, said:
“This research is encouraging adds to a growing evidence body suggesting exercise is an important way we can look after our brain health.

“But awareness of the importance of brain health is low: our own research shows that only a third of people think it’s possible to reduce their risk of developing dementia, compared to 77% who believe they can reduce their risk of heart disease. While there is no sure-fire risk way to prevent dementia, our brains don’t operate in isolation from the rest of our bodies and a good rule of thumb for everyone is that what is good for your heart is also good for your brain.

“As the UK’s leading dementia research charity, Alzheimer’s Research UK is now helping fund work to see how feasible it is for people in midlife to take up exercise as part of a healthier lifestyle, with a view to larger trials that assess the effect on brain health.

“The best current evidence suggests that as well as staying physically and mentally active, eating a healthy balanced diet, not smoking, drinking only within the recommended limits and keeping weight, cholesterol and blood pressure in check are all good ways to support a healthy brain as we age.”

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Quang Tran