Since the first Kloster Seeon meeting on β-secretases in 2013, a handful of BACE inhibitors have entered clinical trials and researchers have learned more about what these proteases do in development and adulthood. What’s the status of the field in the fall of 2016? Check out our coverage of the 2nd Kloster Seeon meeting. Highlights include conditional BACE1 knockouts, updates on non-APP substrates cleaved by BACE, news about BACE’s role in dystrophic neurites, assays to measure off-target effects and—finally—the arrival of BACE1-selective inhibitors.
As research on frontotemporal dementia gathers steam, the international conference hosted its largest gathering ever last month in Munich, Germany. More than 750 researchers shared their latest data on basic science, genetics, and clinical outcome measures. Biomarkers dominated the meeting, as the field prepares for therapy trials by seeking better ways to track pathology in living people. The few trials that have been done thus far, without specific biomarkers, have largely been a bust.
Held July 22 to 28 in Toronto, the Alzheimer’s Association International Conference showcased a field in transformation. At the clinical level, groups from Europe, North America, and Japan are attempting to coalesce around new ways to recruit preclinical populations for large observational and trial platforms for late-onset AD, while the smaller but more established DIAN initiative is growing into a worldwide movement. At the biological level, research is set to expand thanks to funding increasing in response to national plans. Health economics research is pressing in. Topically, tau ruled the roost, though genetics, vascular contributions to dementia, and efforts to define ever-earlier stages of the decades-long disease continuum advanced, as well. On the clinical trials front, the only Phase 3 study appears to have been largely a bust, while some Phase 1 presentations of new antibodies, BACE inhibitors, and a small-molecule tau modifier drew quiet praise.
Researchers who packed the lecture halls for “Common Mechanisms of Neurodegeneration” and “Microglia in the Brain,” joint Keystone Symposia held June 12-16 in Keystone, Colorado, saw old dogmas fall and new ideas and methodologies emerge. Debates ran the gamut from the biophysical nature of toxic proteins to the characterization of microglia in health and disease.
At the third annual Zilkha Symposium, held April 15, 2016, in Los Angeles, scientists from the United States and Europe wrestled with the immense complexity and heterogeneity of Alzheimer’s disease. The program ranged from genetics to clinical symptoms to drug targets. Researchers discussed how genes point to amyloid, tau, and the immune system. They debated the merits of diagnosing Alzheimer’s disease based on symptoms versus biomarkers, and considered a panoply of medications now in trials. Rather than being overwhelmed by complexity, however, researchers were confident that even attacking one of multiple pathogenic pathways in Alzheimer’s could help people with the disease, perhaps soon. Highlights included new approaches to Aβ oligomer morphology, the interplay between amyloid and microbes, and the importance of the brain’s vascular system. Read Amber Dance’s series.
Earlier this month in Washington, D.C., 95 scientists from 23 companies, 19 academic institutions and two regulatory agencies met with funders, advocates and patients and caregivers. The buzz was all about learning from the mistakes and setbacks of drug development in Alzheimer’s disease and getting a collective act together while the FTD field is still young. On what did the group agree? Basic science and longitudinal human studies are advancing apace, but what the fields needs most urgently now to launch more and good trials is a toolbox of biomarkers to subtype FTD disorders and measure target engagement. For their part, the regulators want creative, rigorous science that tries to couple biomarker change to meaningful outcomes, but assured the scientists that no disease is too rare for them to be keenly interested and approve drugs for it. Read Gabrielle Strobel’s series.
Did you know the U.S. National Alzheimer’s Project Act covers Lewy body, frontotemporal, vascular, and mixed dementias, as well? It does, and in March, scientists gathered at the National Institutes of Health to powwow about where we are with these disorders and how best to target research dollars to them. Based on this meeting, research leaders articulated funding priorities for each of these diseases, which will inform both the next bypass budget, and, hopefully, the next Congressional funding allocation for research on these less-studied dementing illnesses.