Key facts
- An experimental drug, diranersen, targets tau protein levels in the brain to potentially slow early Alzheimer's disease.
- Unlike current treatments focusing on amyloid, diranersen aims to reduce the production of abnormal tau.
- Early study results indicated diranersen slowed cognitive decline in some participants, with one dose showing a 26% reduction.
- The drug is administered via injection into the fluid surrounding the spinal cord.
- Side effects were noted, including injection site pain and temporary confusion, but no brain inflammation.
- New research initiatives, including a tau vaccine and other novel approaches, are also being explored.
An experimental drug called diranersen is showing promise in potentially slowing the progression of early Alzheimer's disease by targeting the tau protein, a different mechanism than current treatments that focus on amyloid buildup. Researchers presented findings suggesting that diranersen not only lowers tau levels but also modestly slows cognitive decline, with one small subset of participants showing a reduction comparable to amyloid therapies.
The study, involving approximately 400 individuals with mild cognitive impairment or mild Alzheimer's, found that five out of six cognitive tests indicated slower decline in recipients compared to placebo. Notably, the lowest dose, administered every six months, demonstrated a 26% reduction in cognitive decline, a result considered encouraging despite the study not meeting its primary goal of dose-dependent benefits.
Diranersen, an antisense oligonucleotide, works by instructing a tau-producing gene to generate less of the protein. This approach differs from current infusions or injections of anti-amyloid drugs, as diranersen is injected into the spinal fluid for a more direct path to the brain. Side effects were reported, including injection site pain and temporary confusion, but importantly, no signs of brain inflammation were observed, unlike those sometimes seen with anti-amyloid treatments.
This development is spurring renewed interest in tau-targeting mechanisms, with other novel approaches also under investigation. These include a tau vaccine being tested in a new platform study by the University of California, San Francisco, and an experimental cholesterol-lowering drug, obicetrapib, being explored for its potential to mitigate Alzheimer's risk in individuals with a genetic predisposition.
Companies are also exploring innovative drug delivery methods, such as Denali Therapeutics' approach to use natural transport mechanisms, like iron, to ferry drugs across the blood-brain barrier more effectively.