While recent setbacks in the form of failed clinical trials have clarified that it will be a longer road to effective treatments for Alzheimer’s disease (AD), those setbacks haven’t dimmed optimism for developing diagnostics for the neurodegenerative disorder. Since the dementia associated with Alzheimer’s becomes noticeable later in the course of the disease, the need for earlier diagnostic options is clear. According to The Alzheimer’s Association, the total cost of care for individuals with Alzheimer’s or other dementias in 2018 is estimated at $277 billion, and as such, there are “enormous cost savings, both financial and emotional, that can be achieved with an accurate diagnosis even in the absence of a therapeutic,” says neurological diagnostics company NeuroDiagnostics LLC.
In pursuit of enabling such diagnoses, a partnership is underway to engineer a new method of diagnosing Alzheimer’s disease, while another method has secured Breakthrough Device designation.
Optos plc, a subsidiary of Nikon Corp., and Amydis Inc. have begun a clinical alliance to develop one of Amydis’ eye tests for retinal diagnosis of AD. The partners will work together to develop the test, with Optos applying its proprietary ultra-widefield technology to unite it with Amydis’ proprietary compounds. Financial details for this agreement were not released.
As noted in an Optos press release, “Research shows that damage to the brain [due to Alzheimer’s disease] starts 15 to 20 years before problems become evident … Early and accurate diagnosis could save up to $7.9 trillion in medical and care costs.”
Amydis’ compounds are engineered to detect amyloid proteins in the retina by binding to specific biomarkers and fluorescing, which makes them visible with Optos’ optomap ultra-widefield retinal imaging devices. While traditional retinal imaging can capture between 10 and 100 degrees of the retina, optomap is capable of capturing 200 degrees, with optomap auto-montage reaching 220 degress.
Robert Kennedy, CEO of Optos, said, “We are proud of the ongoing use of optomap imaging devices in clinical research to visualize biomarkers in the retina associated with Alzheimer’s disease. This clinical collaboration with Amydis supports Optos’ vision to help physicians diagnose and monitor disease by studying the retina. We are pleased to work with Amydis in this important alliance and the benefit it may bring to patients suffering from Alzheimer’s disease.”
Further down the pipeline, NeuroDiagnostics LLC recently secured Breakthrough Device designation from the U.S. Food and Drug Administration (FDA) for its DISCERN multiple biomarker test for Alzheimer’s disease. Should DISCERN gain FDA approval, it could be the first approved test that uses multiple biomarkers to identify AD and differentiate it from other dementias, according to a NeuroDiagnostics press release.
As with the Optos and Amydis effort, NeuroDiagnostics is pursuing a test that will enable less-invasive diagnosis earlier in the course of the disease. DISCERN only requires a small skin sample to be performed, as opposed to the most common tests currently in use. The sample is incubated and then expanded to more than a million cells.
“There has been a critical, unmet need for an accurate and simple test for Alzheimer’s disease,” said Dr. Daniel Alkon, principal investigator in the clinical trials for and co-inventor of DISCERN. “Existing methods to identify Alzheimer’s disease have limited accuracy, are expensive and often invasive; those tests that require lumbar spinal tap are frequently avoided by many patients. Until now, a significant number of patients with dementia go undiagnosed—or worse, misdiagnosed. Each of the NeuroDiagnostics biomarkers independently has been found to show high sensitivity and specificity—in both detecting and differentiating AD from other dementias—as confirmed by autopsy validation.”
DISCERN utilizes three novel proprietary biomarkers, all of which the company says have been proven to be highly accurate, “with a sensitivity and specificity greater than 95 percent in both detecting AD and differentiating AD from other dementias … The three biomarkers comprise an AD-Index assay, a Morphometric Imaging assay and a PKC Epsilon assay. The test can determine the level of synaptic loss in the brain before the onset of amyloid plaques or tangles and is accurate even in the earliest stages of the onset of AD (i.e., years 1-4).”
With the AD-Index Biomarker, NeuroDiagnostics explains on its website that a “small nano-peptide that induces Erk1 and Erk2 phosphorylation in fibroblasts,” after which “quantitative imaging of the phosphorylated Erk1 and Erk2 is then used to identify and differentiate Alzheimer’s disease (AD) from non-AD dementia (Non-ADD) and age-matched control (AC) specimens.”
For the second biomarker, “the cultured skin specimen is stimulated with an extracellular matrix composed of an array of macromolecules, forming networks which are dysregulated in AD skin fibroblasts. Networks are rapidly formed for Age-matched control and non-AD dementia cells, but not for AD cells. The rate and extent of network formation can be quantified and is a highly accurate diagnostic biomarker of AD that corresponds to autopsy-demonstrated pathologic hallmarks of AD – amyloid plaques and neurofibrillary tangles.”
As for PKCε (Protein Kinase C ε), a biomarker primarily expressed in the brain and associated with Alzheimer’s pathophysiology, “PKCε-specific antibodies are used with the cultured skin specimen to quantify relative levels of PKCε and to distinguish AD patients from non-ADD and AC patients. AD patients demonstrate a comparative deficit in PKCε and a different response to the ab stimulus when compared to AC and non-ADD. These differences were found to correspond closely in the AD patients to the presence of amyloid plaques and neurofibrillary tangles.”