In Alzheimer's disease research, we may be on the cliff of a critical moment. In clinical trial data released this week, scientists have presented early evidence that symptoms of people who may delay genetic fate at a young age.
Researchers at the University of Washington School of Medicine led the study, which aims to test an experimental anti-amyloid drug called Gantenerumab that can help people with a genetic form of Alzheimer's disease. In a portion of patients who have been treated the longest, the drug appears to reduce their expected symptom risk by 50%. These findings will require follow-up, but outside experts are cautiously optimistic about what this means for the future of treating Alzheimer's.
“The results clearly show that there is hope [Alzheimer’s] Pathology at the preclinical stage of pathology may be effective in slowing down or preventing disease onset,” Thomas M. Wisniewski, director of the Center for Cognitive Neurology at Langone Health at New York University, told Gizmodo.
Gantenerumab is one of many similar drugs developed by scientists for Alzheimer's disease. This is a laboratory-made antibody that targets amyloid beta, one of two proteins that is believed to play a key role in causing Alzheimer's disease (the other is tau). In people with Alzheimer's disease, misfolded versions of amyloid beta accumulate in the brain, forming a hard clump called plaques that eventually become entangled in the organs. In theory, scientists could use drugs such as Gantenerumab, such as breaking down and preventing these plaques from forming, to stop or at least slow down Alzheimer's.
Unfortunately, it was not a smooth journey for this assumption. Many anti-amyloid drugs have shown hope in the early stages, but failed in large trials that tested people who have begun experiencing Alzheimer's symptoms. The list includes Gantenerumab; at the end of 2022, pharmaceutical company Roche closed the development of the drug after a pair of Phase III trials failed.
However, recent anti-amyloid drugs have shown moderate but obvious effects in slowing down Alzheimer's disease, enough to win approval from the Food and Drug Administration. Some researchers, including At Washu Medicine, hope to administer anti-amyloid therapy long before Alzheimer's symptoms develop.
Starting in 2012, researchers and others have launched prevention trials to test anti-amyloids in people with major genetic inheritance of Alzheimer's, a genetic condition that almost guarantees a person's development of dementia sometime between the 30s and 50s. Most of these trials were unsuccessful, except maybe the same as the one from Gantenerumab.
When the initial Gantenerumab study ended in 2020, researchers found that it lowered people's amyloid levels. But it is too early to know whether it delays people's symptoms, as most patients at the beginning of the study are not expected to get sick for another 10 to 15 years. The researchers then decided to publicly provide Gantner tumors to their patients, including taking placebo or other drugs, as part of the extended study.
This is the latest result of the study, published Wednesday in Lancet Neurology, and people are excited.
“Everyone in this study is destined to develop Alzheimer's disease, some of whom have not.” “We don't know yet how long they will remain in symptoms, even years or even decades.”
That is, this study has important warnings.
Wisniewski noted that, on the one hand, these findings only hint at potential preventive benefits. Although the drug may reduce the risk of cognitive decline in the larger asymptomatic population overall, this reduction is not statistically important (probably due to the low number of patients in the study, with a total of 73, Wisniewski said). In the subset of asymptomatic patients who received the longest treatment (average eight years), the drug appears to reduce the expected chances of cognitive decline by 50%. But this subset includes only 22 patients, a smaller sample size.
The trial also ended earlier than many patients expected, as Roche abandoned the drug, while some dropped out of school for other reasons. The drug appears to be generally safe and tolerant, although about one-third of amyloid-associated imaging abnormalities or ARIA is a sign of brain swelling or bleeding. Arias is a known side effect of these drugs, although most episodes do not attract the patient's attention. The two patients did experience severe arias, which prompted the researchers to stop treatment, and they recovered afterwards. During the study period, there were no life-threatening events or deaths.
All in all, this study is not clear evidence that anti-amyloid proteins can work for Alzheimer's. However, because this form is inherently inevitable, these results are the first in clinical trials that suggest that it can be treated. Coupled with the early approval of Lecanemab and Donanemab's classical version of neurodegenerative diseases, there does seem to be something real here.
“We already know from the data from lecanemab and Donanemab that anti-amyloid antibodies (AAAS) can slow down the common Alzheimer’s disease,” Sam Grady, deputy director of the Alzheimer’s disease research center, told Mount Sinai, who told Gizmodo. Grady added: “This article focuses on using different AAAs (Gantenerumab) to prove that similar phenomena are correct in Alzheimer's disease, which occurs early in genetically.
Grady, Wisniewski and the researchers themselves all agree that this is just the beginning. Indeed, prevention trials are now being conducted for early and classical Alzheimer's disease, some of which are run by Washu through its main inherited Alzheimer's network-trial department. These trials are testing approved and updated experimental anti-amyloid drugs that may have a more protective benefit than gantnarumzumab. The researchers were also able to switch many patients in the original extended study to lecanemab, although data from this stage remain to be analyzed.
It's early now, but there may be real hope for this incurable disease.
