An experimental drug called diranersen reduced tau tangles in the cerebrospinal fluid of people with early Alzheimer's disease by 50 to 65 percent and modestly slowed their cognitive decline compared with placebo.
The Research
Diranersen is an antisense oligonucleotide—a synthetic strand of DNA designed to silence a specific gene. It targets the MAPT gene, which produces tau, the protein that forms damaging tangles inside nerve cells in Alzheimer's disease. The drug is being developed by Biogen and was injected directly into patients' spinal cords.
Neurologist Catherine Mummery of the University College London Dementia Research Center presented the Phase II results on July 14 at the Alzheimer's Association International Conference in London. The trial, which began in October 2017, enrolled 416 participants with mild cognitive impairment or early-stage Alzheimer's disease. Participants were divided into four groups: a 60 mg dose every 24 weeks, a 115 mg dose every 12 weeks, a 115 mg dose every 24 weeks, and a placebo. The trial lasted 76 weeks.
Cognitive testing measured memory, problem-solving, and orientation to time and place. The data contained a surprise: all intervention groups declined more slowly than placebo, but the low-dose group showed the slowest decline, with scores dropping 26 percent less than placebo, while the highest-dose group dropped only 9 percent less—despite achieving the greatest reductions in tau.
"It's the age-old question, are these clinically meaningful differences?" said Rob Howard, a psychiatrist at University College London who was not involved in the study. The cognitive changes were, in his words, "pretty tiny." The mismatch between tau lowering and cognitive benefit could stem from the trial's small size or the drug's small effect sizes. Biogen plans to move diranersen into Phase III trials in a larger group.
Why It Matters
Alzheimer's affects over seven million people aged 65 and older in the United States. The approved drugs lecanemab and donanemab target amyloid plaques, not tau. If diranersen succeeds in Phase III and gains FDA approval, it would be the first tau-targeting drug to alter memory in Alzheimer's disease.
For anyone interested in brain health, this research highlights something important: cognitive decline is not one process. Tau tangles are one piece of a complex puzzle that also includes amyloid, inflammation, vascular health, and genetics. A drug that clears tau without proportionally improving cognition reminds us that measuring a biomarker is not the same as measuring how well a person thinks and remembers—and that lifestyle factors like sleep, exercise, and cognitive engagement remain valuable, evidence-backed levers for brain health at every age.
What You Can Do
- Keep your brain active with challenging, varied tasks—novelty and difficulty drive neuroplasticity.
- Prioritize sleep: deep sleep helps clear metabolic waste from the brain, including tau and amyloid.
- Stay physically active—regular aerobic exercise is linked to better cognitive outcomes in aging adults.
- If you or a loved one notice memory changes, talk to a doctor early; interventions work best in early stages.
Source: Science News
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