At a recent meeting on “Research priorities for preventing and treating Alzheimer’s disease and related dementias” (ADRD), convened by the National Academies, one consensus priority on ADRD research was that there needs to be more of it at every stage. Several speakers presented stark numbers on the relative volume of research in cancer and neurodegeneration. Research output, measured in peer-reviewed papers, for dementia is estimated to be around 10,000 papers annually, compared to 150,000 for cancer, while AD clinical trials are also few and far between compared to cancer trials. This final installment of BioWorld’s series on Alzheimer’s explores some of the reasons for this discrepancy along with the latest advances and ongoing efforts to accelerate research and drug development in the field.

Ironically, the first person to be diagnosed with what is now Alzheimer’s disease was missing its major risk factor. When she first began showing symptoms of dementia in 1901, Auguste Deter was not particularly old. Despite Deter’s case, aging is the largest risk factor for developing Alzheimer’s, by a large margin. But “geroscience has not been translated into drugs for Alzheimer’s disease,” Howard Fillit, Alzheimer’s Drug Discovery Foundation co-founder and chief scientific officer, told BioWorld. “We’re just starting to see that cross-fertilization now.”

After decades of trying and dozens of failed trials, amyloid targeting has paid off with the first disease-modifying agents reaching the market. But success does not mean slam dunk. Aduhelm (aducanumab, Biogen Inc.) was dogged by controversy throughout its brief tenure, and Biogen pulled the plug on it in early 2024. Leqembi (lecanemab, Biogen Inc.) has received full approval. In this second installment of a three-part series on Alzheimer’s, BioWorld looks at the nuanced view of amyloid’s role in the disease.

Ironically, the first person to be diagnosed with what is now Alzheimer’s disease was missing its major risk factor. When she first began showing symptoms of dementia in 1901, Auguste Deter was not particularly old. Despite Deter’s case, aging is the largest risk factor for developing Alzheimer’s, by a large margin. But “geroscience has not been translated into drugs for Alzheimer’s disease,” Howard Fillit, Alzheimer’s Drug Discovery Foundation co-founder and chief scientific officer, told BioWorld. “We’re just starting to see that cross-fertilization now.” This first article of a three-part BioWorld series on Alzheimer’s disease looks at how a group of researchers, as well as some startups, are trying to approach Alzheimer’s via an aging lens.

Alzheimer’s disease (AD) is recognized worldwide for its debilitating symptoms of declining cognitive function and gradual memory loss. What remains less clear is exactly what causes the neurodegenerative disease, and how to treat it. “Alzheimer’s disease is characterized by two key pathologies – beta-amyloid plaques and tau neurofibrillary tangles.” Seung-Yong Yoon, CEO of Adel Inc., told BioWorld. “Adel is looking to develop a tau-targeting drug, considering tau has been more correlated with AD symptom progression, and the industry’s need for tau pipelines.”

Deep learning algorithms have enabled the discovery of molecular structures of interest in biomedicine to design treatments against aggressive diseases such as idiopathic pulmonary fibrosis (IPF). Scientists at Insilico Medicine Inc. selected a target for IPF using artificial intelligence (AI), then designed an inhibitor to block it, and tested it in vitro, in vivo, and in clinical trials.

Senisca Ltd., a spinout from the University of Exeter, has raised an additional £3.7 million (US$4.7 million) in funding to support the development of RNA-based senotherapeutics to treat age-related disease.

The third day of the AD/PD 2024 conference in Lisbon started with a plenary lecture given by Professor Howard Fillit entitled, “Translating the biology of aging into new therapeutics for Alzheimer’s disease.” Fillit, a recognized neuroscientist and geriatrician, and co-founder of the Alzheimer’s Drug Discovery Foundation (ADDF), pointed to the geroscience hypothesis which postulates that targeting aging processes may result in preventive and therapeutic options for diseases of old age, including Alzheimer’s disease (AD).

CAR T cells could be repurposed to target senescent cells and delay the effect of aging. A study by scientists at Cold Spring Harbor Laboratory showed how to design them and demonstrated the advantages of this therapy in mice. “We only gave one dose, and we could have benefits [for] really long periods of time,” lead author Corina Amor told BioWorld.

It has been previously demonstrated that genetic variability of thioredoxin reductase 1 (TXNRD1) is associated with aging and age-associated phenotypes. Researchers from MD Anderson Cancer Center have now conducted work to assess the role of TXNRD1 in regulating tissue aging.