Laser-based eye tests now in clinical trials for detection of Alzheimer’s disease have proven successful in spotting early molecular signs of the disease. The commercialization of these tests could ignite future demand for imaging studies of patients suspected of Alzheimer’s.
Laser-based eye tests now in clinical trials for detection of Alzheimer's disease have proven successful in spotting early molecular signs of the disease. The commercialization of these tests could ignite future demand for imaging studies of patients suspected of Alzheimer's.
The optical technology, which has completed phase I clinical studies and is slated next year to enter phase III, could cost as little as $300, low enough to prompt widespread screening, according to its developer, Dr. Lee Goldstein, director of the Molecular Aging and Development Laboratory and associate director of the Center for Ophthalmic Research at the Brigham and Women's Hospital in Boston.
If adopted as a screening tool, the optical tests, which detect amyloid beta proteins in the lens of the eye, could be a boon for medical imaging techniques aimed at diagnosing Alzheimer's disease. Goldstein speculates that the tests could eventually become part of a suite of universal early screening technologies used routinely in an annual physical exam for middle-aged people. If this happens, the detection of molecular signs might be followed by imaging studies to determine whether the disease has taken hold in the brains of patients or to monitor their condition and response to therapy.
PET scans already demonstrate patterns of decreased metabolism in the brain indicative of Alzheimer's disease. These patterns may be apparent years before a physician can confirm the diagnosis and may be used to differentiate Alzheimer's from other types of dementia or depression. Medicare reimbursement has been available for these tests since 2004.
More specific imaging tests that target amyloid plaque in the brain are in the offing. One such test, based on a PET radiopharmaceutical, is in development at GE Healthcare. The company is also working on a synthesizer for efficiently producing this radiotracer onsite, pending its approval by the FDA.
The optical technology that might build demand for such PET studies will be the subject of a plenary talk by Goldstein next week at the annual meeting of the Optical Society of America in Rochester, NY. There he will provide animal data indicating that the test may be so sensitive it can detect the presence of amyloid beta proteins in the lens of the eye even before this pathology is present in the brain.
Goldstein's presentation will build on results provided at last year's meeting showing that laser-based eye tests could detect unusual cataracts composed of the protein. Amyloid beta, when present in the brain, is a hallmark of Alzheimer's disease. Previously, Goldstein and his colleagues had discovered evidence that Alzheimer's was not just a brain disease, but rather a systemic one that also manifests in the lens of the eye.
The amyloid beta proteins that form plaques in the brain and impair cognitive function also build up near the edge of lens, ultimately forming an unusual supranuclear cataract that is very different from more familiar age-related cataracts.
The technology behind these tests is being developed by Neuroptix, a Massachusetts-based biotech firm cofounded by Goldstein, who serves as a consultant to company. Neuroptix has licensed the technology for clinical use.
One test involves low-intensity laser light directed very briefly into the lens. Light scattering detects small clumps of amyloid beta particles there. Animal studies indicate this test can detect the particles that form the unusual cataract associated with Alzheimer's disease, but a cataract need not be present for the amyloid beta proteins to be detected.
"We can pick this up in entirely clear lenses," Goldstein said. "This is exactly what we want to be doing."
Another test uses eyedrops containing a specially designed ligand that specifically binds to amyloid beta proteins. When laser light from the instrument is directed into the lens, the amyloid emits a characteristic light signal detected and analyzed by the technology.
Goldstein emphasizes that these are not imaging tests but rather a "molecular diagnostic" that can detect and analyze suspicious amyloid deposits in the lens. Such a test, employed as a screening tool, offers the potential to serve as a gateway to clinical tests that might follow disease progression and patient response to therapy.
Buoying hopes that the optical technology might serve as a screening tool are studies performed by Goldstein and colleagues demonstrating in mice that signs of the protein appear in the lens before the classic amyloid brain lesion of Alzheimer's disease develops in the brain. This is vitally important, he said, as early detection is the only way that physicians can effectively treat the disease.