At a joint Keystone symposia, microglia continued to twist and turn in the limelight, casting a long shadow as central agents of disease, not mere responders. Researchers embraced the complex reality of mixed pathology, dishing out data from animal models in which Aβ, tau, and α-synuclein mingled and sparked each other’s spread. From a gut-initiated model of Parkinson’s disease to chimeric mice harboring human microglia to a startling conversion of astrocytes to newborn dopaminergic neurons within the brain, researchers upped the ante on disease models and proposed new therapeutic strategies.
Held in romantically beautiful Lisbon, this AD/PD was the biggest thus far, drawing 3,982 attendees from 73 countries, according to Abraham Fisher, its longtime lead organizer. But as the field grows, it has little to celebrate, and the mood reflected that. Trialists were appealing for patience and pointing to deepening clinical trials skills as they learn from continuing setbacks on investigational therapies, most recently of lanabecestat, crenezumab, and aducanumab. Trials targeting tau were not yet reading out, but the medical food Souvenaid posted modestly positive results. At the other end of the bench-to-bedside spectrum, basic science is diversifying. Next-gen genetics is spilling out gene variants which, together with RNAseq, are energizing research into glial and lipid biology. Debate about the amyloid hypothesis, a fixture at AD/PD, evolved toward a focus on genetic variability in how a person’s innate immune system responds to amyloid deposition. Aβ itself? Nothing special about it. It aggregates into an irritant as the brain’s ability to degrade it wanes with age. It starts things off, but other factors later dominate the disease. Or so researchers now think. Read Madolyn Rogers and Gabrielle Strobel’s coverage.
Three years after the Global Alzheimer’s Platform (GAP) Foundation launched GAP-Net, a standing network of clinical trial sites optimized for Alzheimer’s drug studies, the group convened last month in Nashville, Tennessee, to compare notes and share best practices. With 73 sites signed on, three trials currently are up and running. What have they learned? Recruitment outreach works best at the local level, but centralizing other aspects, such as IRB approval, is helpful. Standardized contracts and rater training remain sticky issues, and sites better prepare for an onslaught of newly diagnosed early stage patients expect with upcoming Medicare changes. The mostly young audience enjoyed networking with front-line workers from other trial sites. Read Pat McCaffrey’s coverage in two parts.
Encompassing more than half dozen subtypes, linked to at least four different protein aggregates and at least six distinct genes, frontotemporal dementia would seem like a researcher’s nightmare. And yet, its science is advancing so fast that they have never been more hopeful. Read Tom Fagan’s coverage of the 11th International Congress on FTD, held in Sydney, to catch up on the news.