- A recent study tests a new drug, gantenerumab on people with a genetically inherited form of Alzheimer’s disease.
- For people with this condition, dementia is almost inevitable.
- Gantenerumab helps eliminate one of the neurological hallmarks of Alzheimer’s, called amyloid plaques.
- For some participants, gantenerumab reduced their risk of developing the disease by more than 50%.
A new study provides a well-needed glimmer of hope for treating Alzheimer’s disease.
Focusing on a genetic form of early-onset dementia called dominantly inherited Alzheimer’s disease, scientists have identified a drug that halved some participants’ risk of developing the condition.
While hopeful, scientists need to continue their research in larger groups for longer lengths of time. Below, we outline what the scientists have found and explain some of the unanswered questions.
Although there are many outstanding questions about Alzheimer’s and a significant lack of effective drugs, scientists believe a protein called amyloid-beta plays an important role in the condition.
Although amyloid-beta is present in healthy brains, in people with Alzheimer’s, it clumps together to form plaques, which interfere with the normal workings of the brain. This, scientists believe, is the primary reason for significant cognitive decline.
The amyloid hypothesis inspired scientists to design monoclonal antibody therapies that target and destroy these protein buildups, including drugs like aducanumab, lecanemab, and donanemab.
Research shows that these drugs can
However, until now, scientists have not investigated whether taking monoclonal antibody therapies could prevent or delay the onset of Alzheimer’s in at-risk individuals. The latest study tackles this question and adds supporting evidence for the amyloid hypothesis.
In the latest study, the researchers focused on people with dominantly inherited Alzheimer’s disease (DIAD). These individuals have mutations in certain genes that cause the accumulation of amyloid-beta.
This genetic predisposition means that they have an almost 100% chance of developing Alzheimer’s in early- to mid-adulthood.
Because developing the condition is almost inevitable, these individuals provide a unique model for testing new ways to prevent Alzhemier’s.
The participants in this study initially enrolled in the first-ever trial to try and prevent Alzheimer’s. This trial, which focused on anti-amyloid drugs, was set up in 2012 when the participants had either no symptoms or just mild cognitive symptoms. At this stage, they were within 15 years before to 10 years after their expected age of developing Alzheimer’s.
Coming to an end in 2020, the study showed that gantenerumab significantly reduced levels of amyloid-beta and improved some other markers associated with Alzheimer’s. Despite the positive signs, there were no measurable cognitive benefits compared with the placebo group simply because neither group had developed symptoms yet.
So, the researchers extended the study and upped the dosage to see how gantenerumab might work over a longer time.
Although gantenerumab did not make a significant difference for all groups involved in the study, for some, there were benefits.
For those who had been taking the drug for the longest time — around eight years — the effect was clear. Gantenerumab reduced the risk of developing symptoms by 50%.
Some participants are only just reaching or have only just passed their expected age of disease onset, so as the study continues, this percentage may rise if participants remain symptom-free or fall if they develop the disease.
“Everyone in this study was destined to develop Alzheimer’s disease and some of them haven’t yet,” explains senior author Randall J. Bateman, MD, from WashU Medicine in St Louis, MI in a press release.
“We don’t yet know how long they will remain symptom-free — maybe a few years or maybe decades,” he continues. “In order to give them the best opportunity to stay cognitively normal, we have continued treatment with another anti-amyloid antibody in hopes they will never develop symptoms at all.”
“What we do know is that it’s possible at least to delay the onset of the symptoms of Alzheimer’s disease and give people more years of healthy life,” Bateman concludes.
DIAD appears to develop in a similar way to late-onset Alzheimer’s, but further research is required to understand whether gantenerumab might also prevent this much more common version of dementia.
“I am highly optimistic now,” Bateman says, “as this could be the first clinical evidence of what will become preventions for people at risk for Alzheimer’s disease. One day soon, we may be delaying the onset of Alzheimer’s disease for millions.”
Medical News Today contacted Chris Vercammen, MD, a board certified internal medicine physician and medical director at Remo Health who was not involved in the study.
“The study findings are promising but its important to keep in mind that we are still in the very early stages of this type of research.”
— Chris Vercammen, MD
However, because this study focused on patients who were in the pre-clinical stage, but with a high baseline risk, we need more research, Vercammen said.
“To truly understand the potential of these treatments, extensive further research is required,” he told MNT. “This includes large-scale, randomized trials, particularly in diverse populations and those with late-onset Alzheimer’s.”
Although gantenerumab has been discontinued by Roche/Genentech, other anti-amyloid drugs continue to be investigated.
One of the issues with studying diseases that take decades to develop is that studies on drugs need to be just as long. We need to wait for more data to roll in, but the results of this study provide hope for the future.
Not everyone is as upbeat about the recent results. MNT reached out to Deepak Nair, MD, a neurologist at OSF HealthCare who was not involved in the research. “Unfortunately, the study results are not quite as exciting as we would like.”
Although gantenerumab showed an impressive ability to remove amyloid protein plaques, he explained, “there was no statistically significant impact on clinical ratings of cognitive performance.”
“This is similar to other agents that have been shown to reduce the burden of amyloid plaque in patients with mild cognitive improvement or early stage Alzheimer’s disease,” Nair explained.
He also shared “serious concerns about the role of amyloid plaque in Alzheimer’s disease.” As we mentioned, the amyloid hypothesis of Alzheimer’s disease is still just that: a hypothesis.
“Recent revelations about falsified data in early Alzheimer’s research have raised serious concerns about the role of amyloid plaque in Alzheimer’s disease,” he told MNT. He also raised concerns about so-called amyloid-related imaging abnormalities (ARIA).
ARIA are side effects of anti-amyloid therapies that produce abnormal brain signals on MRI scans. They include fluid accumulation or microhemorrhages. “In the various studies of anti-amyloid drugs, the rate of ARIAs has affected 20–25% of patients,” Nair told us.
According to Nair, symptoms can include:
- headache
- confusion
- nausea and vomiting
- difficulty walking
- worsening cognition
In the recent gantenerumab study, the rates of ARIA were particularly high, possibly due to the increased dosage. Two participants left the study due to these brain scan abnormalities, although they recovered fully once the drug had been stopped.
“Alzheimer’s disease, like all neurodegenerative diseases, is a highly complex process which affects the most complex organ system,” Nair concluded. “There is potential here, but we have much more to learn.”
“The accelerating rise in dementia cases presents a profound challenge, placing immense strain on families and demanding significant resources from state and federal governments,” Vercammen told MNT.
“In this context, studies like the one discussed are important, pushing the dialogue on dementia forward and bringing us closer to effective solutions,” he said.
Talking about next steps, Vercammen continued, “we must continue to prioritize large-scale, randomized clinical trials that encompass diverse populations at different stages of the disease in order to fully understand both the potential rewards and risks of any future treatments.”
