Treatment for Alzheimer’s disease, the devastating condition that affects more than 5 million Americans, has remained notoriously elusive for decades. Now, a small study released by drug company Eli Lilly offers at least a flicker of hope: It shows that the experimental drug donanemab may significantly slow patients’ cognitive decline.
The two-year study — which followed 272 people whose brain scans showed Alzheimer’s — found that patients who took the drug had a 32 percent slower rate of decline than those who received a placebo. “It’s very encouraging because this is the first time a drug of its kind has had positive results in early-stage trials,” says Lon Schneider, M.D., Della Martin chair in psychiatry and neuroscience at the Keck School of Medicine of the University of Southern California. The drug, known as a monoclonal antibody, works by binding to the hard plaque in the brain made from amyloid (a protein associated with Alzheimer’s).
Though these initial findings are promising, Schneider says more data is needed. “It may have been everyone just had a small cognitive decline, in which case the results aren’t as significant,” he says. (The drugmaker has said it will release this information shortly in a peer-reviewed clinical journal.)
But this isn’t the only news Alzheimer’s researchers are excited about. “There are several new drugs either close to getting FDA approval, or in development, that promise to really change the playing field when it comes to treatment of Alzheimer’s disease,” says Marwan Sabbagh, M.D., director of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas. Here are some of the most promising contenders.
Aducanumab: This drug, up for FDA approval, is another monoclonal antibody similar to donanemab that binds to the hard amyloid plaques that are the hallmarks of Alzheimer’s disease. “It will be a game changer if it’s approved, because this will be the first drug shown to actually slow down the progression of Alzheimer’s disease,” Sabbagh says.
Pimavanserin: This antipsychotic drug, already approved to treat hallucinations and delusions in people with Parkinson’s disease, is under FDA review for the treatment of some of the behavioral and psychological symptoms of all dementias. “Research shows that it’s very effective also in treating dementia-related psychosis or hallucinations,” Sabbagh says. “This is important because these sorts of episodes are the main reason patients with Alzheimer’s get placed in memory care facilities. If caregivers can manage these symptoms, more people will be able to stay at home.”
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Atuzaginstat: There’s a growing body of evidence that the bacteria P. gingivalis (the cause of gum disease) can infect the brain and cause Alzheimer’s disease. Atuzaginstat is in clinical trials to see if it can inactivate gingipains, the toxic proteins the bacteria release, which can damage healthy brain cells.
NDX-1017: This drug — administered as a daily injectable — is a small molecule that improves the activity of hepatocyte growth factor (HGF), a protein found in your body’s tissues, including your brain. It’s thought that HGF can strengthen the synapses or connections between your brain cells, thus reversing some of the damage caused by Alzheimer’s disease. Brain wave studies in patients show that the drug works quickly, causing changes in as little as eight days.
ALZ-801: This medication offers an advantage over other drugs in clinical research, because you can take it orally rather than as an injection. Unlike monoclonal antibodies, which grab onto amyloid plaques and eliminate them, this drug attacks earlier in the process, blocking the amyloid from ever forming. Right now, studies are only in people with a high genetic risk of Alzheimer’s who carry two copies of the APOE4 gene. But if this research proves successful, the drug will be tried on other groups in the early stages of Alzheimer’s, Sabbagh says.
Lenalidomide (Revlimid): Used to treat blood cancers such as leukemia or multiple myeloma, this medication is now being studied at the Cleveland Clinic for its potential to treat Alzheimer’s. “Our early research has shown that it will inhibit amyloid plaques in the brains of mice,” Sabbagh says.
Faster Ways to Diagnose Alzheimer’s Are Coming
Right now, most researchers diagnose Alzheimer’s with a PET (positron emission tomography) scan, to measure amounts of amyloid deposits in the brain, or a spinal tap, to gauge amyloid levels in the fluid surrounding the brain and spinal cord.
But the procedures are expensive (making insurance coverage an issue), time-consuming and, with the spinal tap, potentially painful. That’s one reason researchers are on the hunt for a better, cheaper and faster blood test. Arman Fesharaki-Zadeh, M.D., a behavioral neurologist and neuropsychiatrist at Yale Medicine, says that his and others’ blood-test research involves hunting for “abnormal versions of tau proteins,” which would also help in diagnosing the disease at earlier stages. “By the time many folks come to see me, they’ve progressed so far they can no longer qualify for clinical treatment trials, which is heartbreaking.”
But it can also be challenging to measure these sorts of biomarkers in blood, as they exist in very small concentrations, Schneider says. That’s why researchers have turned to ultrasensitive tests, known as assays, to see if they can pick up minuscule amounts of biomarkers like amyloid and tau. A 2019 study in JAMA Neurology found that one such test, an immunoassay by Elecsys, was indeed able to pick up these markers in all stages of Alzheimer’s disease. “The thought is eventually it could become a diagnostic screening tool, like other lab tests we do for other illnesses,” Schneider notes.