Through its Diagnostics Accelerator, the Alzheimer’s Drug Discovery Foundation (ADDF) – a U.S. based non-profit – is committed to accelerating the development of diagnostic tools and biomarkers for Alzheimer's disease and related dementias. With funding from a coalition of philanthropists, including ADDF Co-Founder Leonard A. Lauder, Bill Gates, and Jeff and MacKenzie Bezos, among others, the ADDF will award up to $50 million over the next three years.
A European research collaboration headed by the University of Gothenburg will receive the equivalent of up to SEK 30 million, or $3.2 million U.S. dollars, to develop a blood test where people at risk for Alzheimer’s disease may submit blood samples in most hospitals in the world and be informed with great accuracy if they are beginning to develop the characteristic plaques in the brain, perhaps 20 or 30 years before dementia becomes apparent.
“This represents a further development of a marker we have worked with for a long time and its use is now established as a marker measured in spinal fluid,” says Henrik Zetterberg, a professor of neurochemistry at Sahlgrenska Academy, University of Gothenburg. “We have shown that the marker can also be measured in the blood, but, requires highly sensitive measurement techniques.”
Characteristic plaque in the brain
The marker, known as beta amyloid 42, is a protein normally found in the brain. The protein metabolizes and is then flushed out, primarily into the spinal fluid but also into the blood. Early in the development of Alzheimer’s disease, plaque formation begins, which causes beta-amyloid 42 to adhere to the brain. This leads to a drastic reduction in measurable levels, especially in the spinal fluid, but also in the blood. Previous research from a neurochemistry team at the University of Gothenburg has shown that this reduction in beta-amyloid 42 in cerebrospinal fluid indicates with 96 percent certainty that a person will become ill with Alzheimer’s disease within 10 years.
Henrik Zetterberg is coordinating the project at the University of Gothenburg, and his colleague Kaj Blennow is also one of the heads of research on the project. Other participants include Oskar Hansson at Lund University and José Luis Molinuevo at the Barcelonaβeta Brain Research Center in Spain. The global pharmaceutical company Roche Diagnostics International Ltd.
“We have long worked with Roche to develop a platform, and now we are beginning to approach the accuracy that can be used as a method of routine clinical care throughout the world. We will continue to refine the method, verifying that it really works, and we hope to see it approved for clinical use,” says Zetterberg.
Dr. Howard Fillit, Founding Executive Director and Chief Science Officer of the Alzheimer's Drug Discovery Foundation, says. “These awards represent a true collaboration among renowned clinicians, who are directly involved with patients and understand the disease, scientists who are developing the tests, and diagnostics companies that understand the regulatory pathways – driving research and product development.
“Our goal is to accelerate the development of early and more accurate diagnostic tests, as well as tests that can accelerate and improve the rigor of clinical drug development. “Ultimately, these tests will represent the beginning of precision medicine for Alzheimer’s disease and related dementias,” he says.
Contributing to clinical trials
There is currently no cure or disease-modifying treatment for Alzheimer’s disease, but there are drugs to address symptoms. The goal is to have the new method of analyzing blood tests to predict Alzheimer’s ready in three years. The method will then be used to find people included in major clinical trials already under way or planned for various pharmaceutical candidates to treat the disease.
“This simplified method for finding people with early signs of disease in the brain will facilitate drug discovery, not only for Roche but for all the pharmaceutical companies that are working to find treatments for Alzheimer’s disease,” says Henrik Zetterberg.
The research teams at Lund University and in Barcelona offer access to samples collected from both cerebrospinal fluid and blood of people who have also been studied with other methods and who researchers have a good overall picture of as a result. A parallel effort at Lund University has the goal of improving diagnostics in primary care.
PHOTO: JOHAN WINGBORG