Two billionaires have joined forces in a $30 million effort to develop peripheral biomarkers for the early detection of Alzheimer’s disease and other dementias.
Bill Gates and Leonard Lauder, cofounder of the Alzheimer’s Drug Discovery Foundation (ADDF) and chairman emeritus of Estée Lauder, provided initial funding for the project, dubbed Diagnostics Accelerator. Support from other philanthropists, including the Dolby family and the Charles and Helen Schwab Foundation, will bring the initiative up to its full funding capacity, according to an ADDF press statement.
“Over the next 3 years, we will provide more than $30 million in grants to researchers who are working on the most promising and innovative ideas to help diagnose Alzheimer’s disease [AD] early before the more devastating symptoms occur,” Mr. Lauder said in the statement.
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Researchers at academic centers and nonprofit organizations are eligible to apply for the program; biotech companies and startups are also invited. Letters of intent for the first round of funding are due by Sept. 14, and the final proposals are due Nov. 16. Conducted under the auspices of the ADDF, the program will employ strict scientific review of all proposals and grant priority to blood and other peripheral markers, including saliva, urine, and ocular biomarkers. Neuroimaging and cerebrospinal fluid biomarkers won’t be considered, although researchers may use these as validation tests for their investigational markers.
Target areas include, but aren’t limited to:
- Neuroprotection
- Neurodegeneration
- Protein misfolding
- Synaptic integrity and/or activity
- Vascular injury and blood-brain barrier integrity
- Mitochondria and metabolic function
- Oxidative stress
- White matter changes
The initiative reflects recent emphasis on the critical role of biomarkers in drug development; this is especially important because emerging data paint a clear picture of a long AD prodrome during which the disease might be more amenable to treatment, ADDF’s Howard Fillit, MD, said in the press statement.
“The significance of biomarkers in Alzheimer’s disease research is underscored by recent FDA [Food and Drug Administration] guidelines that recognize the critical role of biomarkers in drug development and shift the research definition of the early stages of the disease to include biomarkers, even before clinical symptoms become apparent. ... Like in cancer today, using the biomarker-specific model of precision medicine, we will be able to predict more accurately which treatment and prevention strategies will work in different at-risk populations of people who have Alzheimer’s disease or other forms of dementia.”
Diagnostics Accelerator will award two general types of grants. Proof-of-principle awards of up to $500,000 will support exploratory analyses of biomarkers in smaller human sample sizes of 50-100. Proposals must be supported by human data that demonstrate that the candidate markers correspond with disease pathophysiology. Preliminary assay validation data for the proposed studies should be included. Successful proof-of principle projects may be eligible for follow-on funding in the form of a validation award.
Validation awards will support exploring biomarkers that need to be tested at a larger scale (500-1,000 samples). These must be supported by a significant extant body of human data that demonstrate that the biomarker corresponds to disease pathophysiology. Validation studies should compare peripheral analytes to quantitative measurements using PET imaging and/or cerebrospinal fluid testing, and not cognition alone. Award amounts will be based on stage and scope of research.
The announcement drew praise from researchers and clinicians.
“I think this is a terrific initiative,” said Michael S. Wolfe, PhD, the Mathias P. Mertes Professor of Medicinal Chemistry at the University of Kansas, Lawrence. “It’s so important to identify those at high risk of developing AD well before the onset of symptoms. All clinical trials for disease-modifying therapies have failed because these have enrolled subjects who already have AD or MCI. Preventing or delaying disease onset [i.e., prophylaxis] is the way forward, but this will require specific predictive biomarkers.”
Richard J. Caselli, MD, a professor of neurology at the Mayo Clinic Arizona in Scottsdale and clinical core director of the Arizona Alzheimer’s Disease Center, agreed.
“I would add that we are still trying to understand how various ‘experiences’ might push us toward Alzheimer’s disease; head injury, diabetes, and air pollution, for example. We know already, based on existing genomic and acquired risk factors, that AD is a complex disease and that many disparate things can influence our risk. Are each of these equally important in each of us or do we each have our own unique vulnerability profile? New biomarkers can help us determine that, and if we are in fact each unique, then maybe prevention strategies need to be personalized.”