Clinical trial results presented at the Alzheimer's Association International Conference show that Biogen's experimental drug diranersen, which targets the tau protein rather than amyloid plaques, successfully reduced tau levels by 50% to 65% and slowed cognitive decline by 26% at its lowest dose. Administered via spinal injection, the drug avoided the brain inflammation side effects associated with existing treatments, though it caused temporary confusion. Researchers are now planning larger Phase III trials and exploring combination therapies.
Diranersen and tau-targeting mechanisms
- ▪Diranersen is administered via injection into the fluid surrounding the spinal cord to provide a direct path to the brain
- ▪Diranersen is an experimental antisense oligonucleotide that instructs a tau-producing gene to produce less tau protein rather than attacking existing buildup
Tau protein and Alzheimer's pathology
- ▪Sticky amyloid beta protein builds up into plaques in the brain about two decades before Alzheimer's symptoms appear, potentially triggering abnormal tau tangles
- ▪Tau protein forms abnormal tangles in neurons that damage nerve cells and are strongly linked to Alzheimer's disease symptoms and cognitive decline
Diranersen clinical trial results
- ▪Diranersen recipients showed a slower rate of cognitive decline across five of six brain tests compared to those who received a placebo
- ▪In a Phase II trial of approximately 400 participants, Biogen's diranersen reduced tau levels in cerebrospinal fluid by 50 to 65 percent
Diranersen dosage and cognitive effects
- ▪The lowest dose of diranersen, administered every six months, resulted in a 26 percent reduction in cognitive decline, showing the strongest effect in the trial
- ▪The diranersen trial did not meet its planned goal because higher doses did not produce greater cognitive benefits than the lowest dose
Diranersen side effects and safety
- ▪Unlike anti-amyloid drugs lecanemab and donanemab, diranersen did not show side effects of brain inflammation or tiny brain bleeds
- ▪Side effects of diranersen included injection site pain and a temporary state of confusion lasting about a week, with no signs of brain inflammation
Future tau therapies and combination approaches
- ▪The University of California, San Francisco opened the Alzheimer’s Tau Platform to test various anti-tau therapies, starting with a vaccine called AADvac1
- ▪Researchers are exploring combination therapies that target both tau and amyloid proteins, as well as other experimental drugs like obicetrapib
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