Drug candidates to treat Alzheimer's disease have failed across the board in clinical trials. To better advance them, the FDA recently released guidelines focused on pushing these drug development efforts into presymptomatic patients. But that's difficult, if not impossible, to do quite yet.
A definitive Alzheimer's disease (AD) diagnosis typically isn't arrived at until after a patient's death, upon brain examination at autopsy. But the industry is pushing hard to arrive at useful biomarkers to identify presymptomatic patients; these include amyloid PET scans and other imagining, cerebrospinal fluid measures of proteins associated with Alzheimer's, speech and brain tests for early cognitive decline, and analyses of retinal images.
Seeing amyloid sooner
For it's part, Sacramento, Calif.-based Neurovision Imaging Inc. is working to develop analytics and technology that detect the disease via retinal autofluorescence to detect amyloid beta (Aβ). It has raised a $15 million series C round to help advance its efforts, with a first close in hand of $11.2 million.
Hedge fund Wildcat Capital Management led the round, with participation from a wide range of strategic investors including Johnson & Johnson Innovation – JJDC Inc., Nikon-SBI Innovation Fund and ophthalmic insurer VSP Global as well as Whittier Ventures.
The detection of amyloid beta plaques, which are distinctive of AD, in retinal imaging could provide a means of early detection. However, the relationship of the appearance of these plaques, in the brain or the retina, to the progression and severity of disease isn't well established yet.
Neurovision is working on clinical testing to seek validation and regulatory approval for its approach to detecting amyloid pathology via retinal imaging. It's been working with a couple of biopharmaceutical companies in pursuit of that effort J&J's Janssen and Eli Lilly. The startup is also in talks with other companies around drug development partnerships.
On the Janssen deal, "the collaboration was designed to enable Neurovision to further validate its retinal imaging technology and develop its technology for potential early detection and monitoring of amyloid pathology related to Alzheimer's disease," Neurovision CEO Steven Verdooner told BioWorld MedTech.
"The collaboration was intended to help Neurovision further develop the foundation for wide, global adoption of its technology, including participation in Janssen clinical trials. The agreement called for Janssen to provide an initial upfront payment as well as payments for participation in clinical trials and also a milestone payment for regulatory approval," he added.
Testing the thesis
Neurovision's technology is part of Janssen's ongoing CHARIOT:PRO clinical trial, which is a prospective, non-interventional trial of 700 patient aged 60 to 85 over up to four years who are at various risk levels for the development of AD. It's designed to describe the baseline characteristics and how cognitive and functional abilities change overtime.
It includes an ancillary Neurovision study to explore the correlation between retinal amyloid beta plaques identified via its technology, as well as compared to PET scans and cerebrospinal fluid testing in 42 patients identified as at-risk for Alzheimer's disease.
With Eli Lilly, Neurovision technology is being used in a phase III trial of its solanezumab to treat Alzheimer's disease, which is also being backed by the National Institutes of Health (NIH). Neurovision joined that ongoing A4 (Anti-Amyloid Treatment in Asymptomatic Alzheimer's) study last year. It is slated to continue through mid-2022. After an earlier trial for solanezumab failed, Lilly opted to push earlier into disease progression and to increase the candidate dosage in the A4 trial.
Last year, researchers at Cedars-Sinai Hospital and Neurovision published in JCI Insight on data from a 16-patient feasibility trial of the technology. It also examined the brains of 37 patients, 23 with confirmed AD and 14 controls. (See BioWorld MedTech, Aug. 23, 2017.)
They found that using autofluorescence imaging to identify beta-amyloid plaques identified a 4.7x increased retinal plaque burden in Alzheimer's patients, as compared to controls. The researchers reported that this was the first attempt to do a histologic quantitative analysis of retinal plaque clusters to identify the most toxic forms of beta-amyloid. They also demonstrated an algorithm designed to quantify retinal autofluorescence that identifies Alzheimer's patients.
The Neurovision approach is based on a 2010 publication by Yosef Koronyo on the discovery of amyloid beta plaques in the retina. The initial work was in transgenic mouse models and human cadaver retinal tissue. The company then spent the next few years translating this out of the lab by developing the device and technology for in vivo imaging.
The system is expected to be used by physicians as an aid to the assessment of amyloid status. It is in the process of being tested in combination with – and in comparison to – other potential biomarkers, such as PET imaging of plaques in the brain.
Neurovision is still in the midst of assessing the best practices use of its technology, but it expects that amyloid beta will be found to build up in the brain at least 20 years in advance of cognitive decline. So, any screening testing for AD would potentially begin around the patient age of 50 or 60.
Using analytics of retinal images to create population disease screening tools is advancing on a number of fronts, not just with Neurovision. The retina is increasingly be viewed as a window into the brain, as well as onto metabolic and vascular health.
Iowa startup Idx LLC recently received the first FDA nod for an autonomous AI system to diagnose diabetic retinopathy from retinal images. It already has several software prototypes of AI diagnostics in additional indications, including an AD risk assessment tool. (See BioWorld MedTech, April 12, 2018.)
Ultimately, the Neurovision system is expected to be useful not only in clinical trials, but also as a population screening tool for Alzheimer's disease. The underlying imaging only requires about 10 minutes are so and is widely available.
"Neurovision's groundbreaking technology provides for the important possibility of detecting neurodegenerative diseases earlier through the discovery of symptoms in the eyes," said Steve Baker, president of Eyefinity, which is part of omnipresent vision insurer VSP Global that has a network of 39,000 optometrists.
He added, "In the end, this is about leading to better health outcomes and more coordinated patient care. We believe Neurovision's technology represents a great opportunity for optometry, underscoring the critical role the eye doctor plays within an increasingly integrated health care system."