# Experimental Drug Targets Alzheimer’s From a New Angle, Early Data Show Promise
Scientists hunting for better ways to fight Alzheimer’s disease say an experimental therapy that attacks a different brain protein than today’s leading treatments has produced encouraging — if not yet conclusive — results in a mid-stage clinical trial.
The drug, known as diranersen and developed by Massachusetts-based Biogen, targets tau, a protein long implicated in the destruction of brain tissue in Alzheimer’s patients but one that has proven notoriously difficult to treat. ,Tau is one part of a toxic duo fueling Alzheimer’s, but prior attempts to develop drugs that can target the protein have failed. Two Alzheimer’s drugs, lecanemab and donanemab, try to clear buildup of the better-known amyloid protein and can modestly slow cognitive decline.,
Findings from Biogen’s Phase 2 study, called CELIA, were presented Tuesday at the Alzheimer’s Association International Conference in London, drawing significant attention from researchers who have spent years searching for a viable way to intervene in tau’s destructive path through the brain.
## A Different Approach to an Old Problem
,The new findings suggest Biogen’s diranersen did more than lower tau levels — the study of about 400 people found signs that it also slowed cognitive decline, in one small subset enough to be comparable to amyloid therapy., Biogen has already signaled it intends to move forward with additional testing. ,Biogen is planning a larger study to try to prove the drug’s benefit.,
Unlike lecanemab and donanemab, which are delivered through the bloodstream and work by clearing sticky amyloid plaques that build up in the brain years before symptoms emerge, diranersen takes an entirely different route. It is ,an antisense oligonucleotide that blocks the production of tau by binding to its precursor mRNA,, rather than attacking tau buildup after the fact. Instead of scrubbing out existing toxic protein, the drug essentially turns down the body’s own manufacturing of it, giving the brain’s natural waste-clearing systems a better chance to keep up.
The therapy is also administered differently than existing Alzheimer’s drugs — through an injection into the fluid surrounding the spinal cord rather than an infusion, offering what researchers describe as a more direct pathway into the brain.
## Encouraging Numbers, With a Twist
According to data shared at the conference, the strongest results came not from the highest dose tested, but the lowest one. ,Diranersen demonstrated efficacy across all studied doses at 18 months, with the 60 mg dose showing the strongest response, slowing cognitive decline by 42% on one cognitive test, 50% on another, and 26% on a broader clinical dementia rating scale compared to placebo.,
That outcome caught many in the field off guard, since it defied the usual assumption that higher doses of a drug produce stronger effects. ,The study failed to meet its primary endpoint of demonstrating dose-response related effects, though the new data showed strong biomarker effects, including reductions in CSF tau and tau PET, as well as clinical effects at lower doses, raising important questions about the optimal dose and design of future trials.,
Even so, the biomarker findings alone were seen as historic. ,Diranersen became the first tau-directed therapy to show robust reductions in both cerebrospinal fluid total tau, ranging from 50% to 65%, and brain tau pathology measured by PET imaging.,
Researchers not involved in the study cautioned that the unusual dosing pattern needs further explanation before any conclusions can be drawn about the drug’s ultimate effectiveness. ,The central unanswered question from the study is the discordance between the biomarker and clinical findings, with higher doses leading to greater tau reduction while the lowest dose showed the strongest clinical signal.,
Still, the overall tone from scientists at the conference was one of cautious optimism. ,Researchers noted these are the first data from a randomized trial to show a tau-targeting drug producing both a robust biomarker effect and a signal of clinical benefit.,
## Safety Profile and Next Steps
As with any new therapy, safety monitoring remains a key part of the ongoing evaluation. ,The safety profile was broadly consistent with earlier studies, showing similar overall adverse event rates but a higher rate of serious adverse events in the highest-dose group.,
Despite the unresolved questions about dosing, Biogen appears confident enough in the results to push the drug toward larger, more definitive testing. ,Based on the growing and consistent body of evidence from earlier-phase studies, Biogen plans to advance diranersen into confirmatory Phase 3 development., Company officials have called the trial’s biomarker results “unprecedented,” according to comments made by a Biogen clinical development executive ahead of the presentation.
## Part of a Broader Push Against Tau
Diranersen isn’t the only tau-focused effort underway. A separate, federally funded research initiative — the Alzheimer’s Tau Platform based at the University of California, San Francisco — recently launched a first-of-its-kind trial structure designed to test multiple experimental anti-tau therapies, including a vaccine, both alone and alongside existing amyloid-targeting drugs. That effort is expected to expand to additional research sites and eventually include people who show biological signs of Alzheimer’s risk but have not yet developed symptoms.
Alzheimer’s disease remains the leading cause of dementia worldwide, affecting more than 7 million Americans and tens of millions of people globally. While amyloid-targeting drugs approved in recent years have offered modest benefits, the search for treatments that address tau — believed by many scientists to be the protein most closely tied to the actual onset of symptoms — has been a major unmet goal in neurology research.
For now, doctors and researchers say the CELIA results represent a meaningful, if preliminary, step forward. Whether diranersen ultimately proves it can slow the march of Alzheimer’s disease in a larger, more rigorous trial will take years to determine — but for a field starved of new therapeutic strategies, Tuesday’s findings offered a fresh reason for hope.