The decades-long search for effective ways to treat or prevent Alzheimer's disease is littered with failures. 5.7 million Americans are already affected by this form of dementia without a lifeline. The rest of us can only hope that we are not among the 1
But precision medicine – an approach that changes the treatment of cancer and produces targeted therapies for a variety of diseases – could open new avenues for the treatment of Alzheimer's disease. And new ways to test experimental treatments promise to identify faster which treatments work and, perhaps, the patients they work best for.
This week, dementia specialists met at the International Conference of the Alzheimer's Association in Chicago to discuss the state of the field. And researchers have found some hope in developing new therapies for Alzheimer's disease in both precision medicine and innovative experimental designs.
These approaches raised the expectation that at least two experimental drugs – one called BAN2401 and the other Anavex 2-73 – would be successfully treated with some Alzheimer's.
In the case of BAN2401, the successful preliminary finding of a study that has surveyed 856 patients with early Alzheimer's disease has revived a hypothesis that persists despite losing losses: reducing lumps of proteins called amyloid plaques In the brain of people with Alzheimer's accumulate, their symptoms of memory loss and cognitive confusion can slow down or reverse.
With an innovative clinical trial design, the American and Japanese companies that developed BAN2401 for over 18 months found patients receiving the highest doses of the drug had dramatic reductions in amyloid plaque deposits in the brains. Compared to subjects receiving placebo, the highest dose patients showed a 26 percent decrease in clinical decline at 18 months.
As the study of BAN2401 progresses, its "adaptive design" ensures that new volunteers are recruited. They were more likely to be in the arms of the process that showed the greatest promise. While some scientists find it controversial, clinical trials that are looking for promising preliminary findings have a high-ranking advocate in the Trump Food and Drug Administration: Commissioner Scott Gottlieb.
"Alzheimer's studies need to evolve," James A. Hendrix, director of global scientific initiatives at the Alzheimer's Association. "We need to try new things and learn from other diseases," he added, including fields like cancer, where new targeted therapies deliver cures for selected groups of patients.
Distinguishing Between Probable and Unlikely Patients "It's an exciting new way to think about new treatments for Alzheimer's," Hendrix said. "Maybe a single size is not the best approach," he added.
In a first attempt to apply the principles of precision medicine to Alzheimer's disease, researchers this week reported on a small study of Alzheimer's patients carrying some "viable genetic variants". In these patients, Anavex 2-73 appeared to slow early cognitive decline and possibly even reverse it.
The new results are from a clinical trial designed to test the safety of Anavex 2-73, involving only 32 patients with mild to moderate Alzheimer's disease. So it's too early to announce the success of this experimental drug.
But the researchers added an extra step to their safety study: Sequencing of Genome of Subjects. They hoped to find genomic signatures in some patients, which would make them more likely to respond positively to the drug.
While researchers combed through more than 33,000 genes, they had a pretty good picture of what molecular processes (or pathways) Anavex 2-73 worked on. So they knew what they were looking for: genetic variations that probably affected the effects of Anavex 2-73 and made the treatment unsuccessful. They found two such genetic variants that occurred in about one-fifth of humans.
When Anavex researchers narrowed the pool of subjects to those whose genetic makeup was consistent with their mode of action, they found those subjects who received the medications for 57 weeks had "clinically meaningful" improvements in their ability to establish day-to-day activities and continue.
A major new study on Alzheimer's disease begins in Australia and North America. The experimental medication is also being tested as a potential treatment for dementia associated with Parkinson's disease, Rett syndrome and Fragile X syndrome.
The idea that a drug used to treat Alzheimer's disease in some dementia patients might work well in others coincides with a growing sense; first, that Alzheimer's can be many different diseases. But it also fits in with the notion that genetic factors, alone or collectively, make some vulnerable to Alzheimer's and protect others.
In precision medicine, sometimes called personalized medicine, researchers are working to identify genetic factors that trigger or contribute to a disease and to establish a medicine that targets the downstream effects of these nefarious genes. They then use genomic sequencing technologies to identify only those patients who carry the characteristic genetic signatures on which their drug works. More often than not, these medicines are expensive and they do not work for everyone. But if the right patients get the right medicine at the right time, the treatments are more effective and have fewer side effects.
"If you use a biomarker that can be detected in a few hours or days with a polka dot test, you can enrich a study – just list the topics that are most likely to respond to it – and of course, improve your chances of success." said Christopher Missling, founding director of Anavex Life Sciences Corp.
Such new approaches to the treatment of dementia "Dr. Deepak Bhatt, an expert on adaptive experimental designs and precision medicine."
"Identifying which patients could benefit from a novel biomarker or genetics therapy is likely to play a big role. Part of how medicine will be individualized in the future – so-called precision medicine," said Bhatt, the interventional cardiovascular program at Brigham and Women's Hospital in Boston.
"This approach can be particularly for therapies that have side effects or are expensive, and while additional confirmatory studies are needed for this particular Alzheimer's drug before clinical use, the potential of personalizing care for such a devastating disease is exciting. "
Alzheimer's drug study offers new hope, but also uncertainty