Green tracer may detect ATTR protein deposits at routine eye exam
Approach could aid FAP, other ATTRs when treatment most likely effective
Applying a fluorescent green tracer called AMDX-9101 during a routine eye exam may enable the detection of the toxic transthyretin protein deposits that cause symptoms of transthyretin amyloidosis (ATTR), a group of conditions that include familial amyloid polyneuropathy (FAP).
It’s too early to know if the approach would work in a clinical setting, but data suggest the tracer could allow doctors to diagnose FAP and other forms of ATTR at an early stage, when treatments are most likely to be effective.
“Developing a simple topical [locally applied] eye test to detect ATTR can potentially transform early diagnosis of ATTR and enable more people to benefit from available treatments,” Stella Sarraf, PhD, CEO and founder of AMDX-9101 developer Amydis, said in a company press release.
AMDX-9101 study findings will be presented by Tatyana Milman, MD, an ophthalmologist who’s been involved in the tracer’s development, at the American Association of Ophthalmic Oncologists and Pathologists annual meeting, Oct. 18, in Chicago. Milman is a professor of ophthalmology and pathology at Wills Eye Hospital.
ATTR comprises a group of conditions wherein transthyretin becomes misfolded and forms toxic deposits called amyloid fibrils, which build up in tissues, causing damage. The disease most often affects the nerves outside the brain and spinal cord, which is a hereditary form called FAP, and the heart, where it’s referred to as ATTR cardiomyopathy.
Other parts of the body can also be affected, however, including the eyes. Amyloid fibrils building up in the eyes can cause a range of symptoms, from dry eyes and blurry vision to changes in eye blood vessels and vision-threatening complications such as glaucoma, or damage to the nerves due to increased pressure inside the eyes.
Approach may yield earlier diagnosis
Treatments are available to slow the progression of FAP and other forms of ATTR, but how well they work depends on how early the disease is diagnosed. ATTR is often underdiagnosed, so many patients aren’t treated until their symptoms have already progressed.
“I investigate the ocular [eye] manifestations of [whole-body] amyloidosis in patients and have a clear understanding of the dire need for better noninvasive diagnostics for [whole-body] amyloidosis disorders,” said Jose Pulido, MD, a member of Amydis’ science advisory board and an ophthalmologist who’s been involved in AMDX-9101’s development.
Driven by the idea that “the eyes are windows to the body,” Amydis developed AMDX-9101 as a small-molecule tracer that could screen for transthyretin amyloid fibrils in the conjunctiva, the clear membrane that protects the eyes.
Once attached, the tracer makes the deposits glow green under a standard eye imaging device. If using the tracer could be added to workflows already established in eye care practice, it could represent a noninvasive, effective way to detect the disease at early stages, when symptoms may not yet be manifesting overtly.
“It is my belief that the Amydis tracer will improve patient outcomes by identifying amyloidosis at earlier stages and helping to personalize treatment plans,” said Pulido, who’s also had roles at Wills Eye, Thomas Jefferson University, and the Henry and Corrine Bower Memorial Laboratories for Translational Medicine.
Research by Milman, along with Pulido and other researchers, showed that mixing together AMDX-9101 and transthyretin clumps in a lab dish led to a bright green fluorescent signal. This was also observed when researchers added AMDX-9101 to an eye of a deceased FAP patient and an eye sample from a person with other forms of hereditary ATRR. Testing on a pig’s eye showed the tracer could be detected using a standard eye imaging device.
The findings supported applying AMDX-9101 to the eye during a simple eye exam as a potential way to diagnose FAP and other forms of ATTR.
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