For decades, the pharmaceutical industry\u2019s battle against Alzheimer\u2019s disease has been largely defined by a singular focus on clearing amyloid plaques. However, new data presented Tuesday suggests the next breakthrough may come from targeting the other half of the disease\u2019s \u201ctoxic duo\u201d: a protein called tau.<\/p>\n
Researchers at the Alzheimer\u2019s Association International Conference in London reported that an experimental drug from Biogen, known as diranersen, successfully lowered levels of tau protein in the brain. More significantly, the study provided early evidence that the drug could slow cognitive decline in patients with early-stage symptoms, potentially offering a new mechanism of action that differs fundamentally from current blockbuster treatments.<\/p>\n
While existing therapies like lecanemab (Leqembi) and donanemab (Kisunla) work by scrubbing the better-known amyloid protein from the brain, diranersen takes a more preventative approach. It is classified as an antisense oligonucleotide\u2014a type of precision medicine that doesn’t just attack existing protein buildup but instead provides genetic instructions to the body to produce less of the protein in the first place.<\/p>\n
\u201cIf you lower tau production, you are lowering the amount of the abnormal tau that needs to be cleared by the microglia, by the clearance mechanism in the brain,\u201d explained Dr. Cath Mummery of University College London, who led the study. \u201cAnd so you are enabling the normal clearance mechanism to have more capacity to clear the tau.\u201d<\/p>\n
The study, which followed approximately 400 participants with mild cognitive impairment or mild Alzheimer\u2019s, revealed a nuanced set of results. Biogen and its partner, Ionis Pharmaceuticals, had previously noted a \u201ccounterintuitive surprise\u201d in the data: the lowest dose of the drug, administered just once every six months, appeared to have the most potent effect. Because higher doses did not yield greater benefits, the study technically missed its primary goal of showing a traditional dose-response relationship. <\/p>\n
Despite that statistical hurdle, the clinical signals were encouraging. Across five of six different cognitive assessments, patients receiving diranersen saw their memory and thinking skills worsen more slowly than those on a placebo. In the most successful test group, the drug was associated with a 26% reduction in cognitive decline\u2014a figure that Mummery noted is \u201capproximately the same\u201d as the efficacy seen in the landmark trials for amyloid-clearing therapies.<\/p>\n
The delivery method also marks a departure from current standards. While amyloid drugs are typically administered via intravenous infusions or subcutaneous injections into the bloodstream, diranersen is injected directly into the fluid surrounding the spinal cord. This provides a more direct pathway to the central nervous system, bypassing the restrictive blood-brain barrier that often limits the effectiveness of neurological drugs.<\/p>\n
\u201cThis is really quite promising if it were to hold up\u201d in larger, late-stage clinical trials, said Jessica Langbaum of the Banner Alzheimer\u2019s Institute in Phoenix. Dr. Reisa Sperling of Mass General Brigham added that while it is still \u201cearly days,\u201d the results are likely to \u201creinvigorate interest and investment in lots of tau mechanisms.\u201d<\/p>\n
The industry\u2019s pivot toward tau comes as scientists increasingly believe that while amyloid plaques begin forming 20 years before symptoms appear, it is the subsequent development of tau \u201ctangles\u201d that actually triggers the death of neurons and the onset of dementia. This shift is fueling a wave of diverse research efforts. For instance, the University of California, San Francisco, recently launched the Alzheimer\u2019s Tau Platform, a federally funded study testing various treatments, including a vaccine called AADvac1 designed to train the immune system to fight toxic tau.<\/p>\n
Other firms are exploring even broader connections. NewAmsterdam Pharma is investigating whether its cholesterol-lowering drug, obicetrapib, might mitigate Alzheimer\u2019s risk in carriers of the APOE4 gene, which is linked to both lipid processing and protein buildup in the brain. Meanwhile, Denali Therapeutics, led by CEO Ryan Watts, is developing \u201ctransport vehicle\u201d technology to help drugs more efficiently cross the blood-brain barrier by \u201chitching a ride\u201d on the body\u2019s natural iron transport systems.<\/p>\n
For Biogen, the diranersen data represents a critical step in diversifying its neurobiology portfolio. While the drug did cause some temporary side effects, such as injection site pain and short-term confusion, it notably did not show signs of the brain inflammation often associated with amyloid-targeting drugs. Biogen is now moving forward with plans for a larger, more definitive study to prove the drug\u2019s clinical benefit for the more than 7 million Americans currently living with the disease.<\/p>\n","protected":false},"excerpt":{"rendered":"
For decades, the pharmaceutical industry\u2019s battle against Alzheimer\u2019s disease has been largely defined by a singular focus on clearing amyloid plaques. However, new data presented Tuesday suggests the next breakthrough may come from targeting the other half of the disease\u2019s \u201ctoxic duo\u201d: a protein called tau. Researchers at the Alzheimer\u2019s Association International Conference in London …<\/p>\n","protected":false},"author":1,"featured_media":2864,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_sitemap_exclude":false,"_sitemap_priority":"","_sitemap_frequency":"","footnotes":""},"categories":[3],"tags":[5025,5023,5022,5018,5024,5021,5019,5020],"class_list":["post-2862","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-business","tag-alzheimers-association-international-conference","tag-amyloid-protein","tag-antisense-oligonucleotide","tag-biogen","tag-blood-brain-barrier","tag-cognitive-decline","tag-diranersen","tag-tau-protein"],"_links":{"self":[{"href":"https:\/\/nile1.com\/en\/wp-json\/wp\/v2\/posts\/2862","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nile1.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/nile1.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/nile1.com\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/nile1.com\/en\/wp-json\/wp\/v2\/comments?post=2862"}],"version-history":[{"count":1,"href":"https:\/\/nile1.com\/en\/wp-json\/wp\/v2\/posts\/2862\/revisions"}],"predecessor-version":[{"id":2863,"href":"https:\/\/nile1.com\/en\/wp-json\/wp\/v2\/posts\/2862\/revisions\/2863"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nile1.com\/en\/wp-json\/wp\/v2\/media\/2864"}],"wp:attachment":[{"href":"https:\/\/nile1.com\/en\/wp-json\/wp\/v2\/media?parent=2862"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nile1.com\/en\/wp-json\/wp\/v2\/categories?post=2862"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nile1.com\/en\/wp-json\/wp\/v2\/tags?post=2862"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}