It’s not clear if monoclonal antibodies can be used to delay the onset of Alzheimer’s symptoms for those without symptoms. DIAN-TU is a trial that tests the effectiveness and safety of various treatments on people who have a genetic version of Alzheimer’s.
An experimental drug is showing promising results in reducing Alzheimer’s dementia risk in those who are destined to get the disease by their 40s or 50s. DIAN-TU at Washington University School of Medicine, St. Louis has found that amyloid deposits in the brain can be removed before they cause symptoms.
This international study examined 73 people with mutations leading to an excessive production of amyloid, which makes them more likely to get Alzheimer’s disease in their middle years. The treatment was able to reduce the risk of Alzheimer’s symptoms in 22 people who had no cognitive problems at the start of the study. They took it for eight years on average.
Randall J. Bateman is the senior author and Charles F. & Joanne Knight Professor of Neurology, WashU Medicine. Everyone in the study had a predetermined Alzheimer’s diagnosis, but some have not yet. It’s not yet clear how long the patients will be symptom free – perhaps a few decades or years.
“We have given them another anti-amyloid to give them the best chance of staying cognitively normal. This is in hope that they never experience symptoms. We know that Alzheimer’s symptoms can be delayed and people will live longer.
These findings confirm the amyloid theory of Alzheimer’s, according to which removing amyloid deposits from the brain is the first treatment for dementia.
Researchers evaluated an anti-amyloid experimental drug in this study to see if it could prevent dementia.
In 2012, the Knight Family DIANTU001 trial began. It was the first global attempt at preventing Alzheimer’s. The trial focused on anti-amyloid drug testing in mild cognitive decline or those with no cognitive impairment within 10 to 15 years of their predicted Alzheimer’s disease onset, based on the family history.
In the study, gantenerumab (an anti-amyloid medication) was found to reduce amyloid in the brain while improving Alzheimer’s related protein measurements. Researchers could not confirm any cognitive benefit in participants who did not show symptoms, as they had yet to experience any decline. They decided to investigate the matter further by extending their study of the drug using higher dosages and longer treatment times to determine if they could delay or prevent cognitive decline.
The DIAN-TU study extension included all participants who had a genetic mutation associated with a high risk of Alzheimer’s disease, regardless of the original treatment they received. Researchers used the data of untreated participants in a similar study (DIAN Observational), and the DIAN TU trial that did not join the extension to compare groups.
This extension, originally planned to last three years, ended in early 2023 when Roche/Genentech stopped gantenerumab’s development in 2020. The decision was made after Phase 3 results showed that the drug did not significantly slow Alzheimer’s disease progression for early symptoms. Participants in the extension trial had been receiving treatment on average for 2.6 years when it ended.
Researchers found after analyzing data that removing amyloid brain plaques prior to the appearance of dementia symptoms can delay the onset of the disease and its progression. The results, however, were statistically significant only for those who began treatment with no symptoms at all and received the most time.
Participants who took gantenerumab for only the two-to-three year extension study have not shown any cognitive benefit. The group that received treatment for eight years on average showed, however, that early intervention may have been crucial in preventing Alzheimer’s. The potential benefits of early, prolonged interventions are highlighted.
The treatment of the group that received the most treatments reduced symptoms in 50%. The calculation took into account how many people developed symptoms, and the age at which they first appeared. Effect size can change with time. Participants who are symptom free beyond the expected age of onset will have a larger effect, while participants who become ill later could decrease it.
Antibiotics, vaccines can reduce the risk of dementia
Gantenerumab, and other similar drugs can cause a side effect known as amyloid related imaging abnormalities. This is a small brain bleeding or swelling that may be detected in scans. The majority of cases resolve with no symptoms. However, some cases can be serious and have even led to death.
The higher extension doses were responsible for the higher ARIA rate (30% as opposed to 19%). After stopping the drug, two participants recovered from severe ARIA. The drug was safe and did not cause any serious adverse events.
The Alzheimer’s Association funded the Amyloid Removal Trial at WashU Medicine’s Knight Family DIANTU. Most participants started taking lecanemab after gantenerumab had been discontinued. This FDA-approved drug is used to slow cognitive decline among symptomatic dementia patients.
Researchers are still analyzing the data from this stage and have requested NIH funds to finish the study. This grant is under review.
Bateman, along with his colleagues, believe that the findings of this trial will help prevent and treat all forms of Alzheimer’s. Amyloid builds up in the mind about 20 years prior to cognitive problems appearing. Also, the results of early-onset Alzheimer studies have been confirmed by late-onset Alzheimer research.
Unraveling the key mechanism of Alzheimer’s disease
If late-onset Alzheimer’s prevention trials show similar results as the DIAN-TU trial, Alzheimer’s treatments could soon be available to the general public. Bateman is saying. I am very optimistic, because this is the first evidence that could lead to preventions of Alzheimer’s in people who are at high risk. We may one day be able to delay the Alzheimer’s disease onset for millions of people.
Other anti-amyloid medications are evaluated to prevent Alzheimer’s Disease in the absence of gantenerumab.
These preliminary results clearly indicate the role that lowering beta amyloid could play in preventing Alzheimer’s. Maria C. Carrillo PhD is the chief scientist and medical affairs leader at Alzheimer’s Association.
The Alzheimer’s Association is eagerly anticipating replication, expansion, and extension of this truly groundbreaking and unprecedented research. We have invested a lot to ensure that these important scientific issues can be explored. These discoveries are a great example of why research on Alzheimer’s disease and other diseases causing dementia must continue to expand and accelerate.
Journal Reference
- Prof Randall J Bateman. Yan Li. Prof Eric M McDade. The safety and efficacy in long-term treatment of gantenerumab for dominantly inherited Alzheimer’s disease. An open-label expansion of the DIAN-TU platform trial, phase 2, 3, randomized, double blinded, controlled by placebo, multicentre. The Lancet Neurology. DOI: 10.1016/S1474-4422(25)00024-9
