Trial to Detect Alpha-Synuclein Deposits in Patients’ Eyes Underway
Tracer intended to aid in diagnosing Parkinson's, monitoring patients
A Phase 1/2a clinical trial testing the ability of AMDX-2011P to safely detect abnormal protein deposits in the retina of adults with Parkinson’s disease and amyotrophic lateral sclerosis (ALS), possibly allowing earlier diagnosis and easier patient monitoring, has dosed its first participants.
These proteins comprise alpha-synuclein in Parkinson’s and TDP-43 in ALS, and they progressively build to toxic levels in the central nervous system (CNS; the brain and spinal cord) of patients.
The retina — the innermost, light-sensitive eye layer that sends vision signals to the brain — is increasingly considered a “window to the brain,” as it has been shown to reflect brain changes in several neurodegenerative diseases. Because the eye is translucent, it can be visualized in an easy and noninvasive manner.
AMDX-2011P, a small molecule being developed by Amydis, is a novel contrast dye, called an ocular or retinal tracer. It is designed to “light up” abnormal deposits of proteins in the retina that characterize certain neurodegenerative diseases. As such, the retinal tracer has the potential to be an early diagnostic test and a tool to monitor disease progression or treatment response during a standard eye exam.
Diagnosing Parkinson’s at early stages, accurately and more easily, is goal
“AMDX-2011P is the first imaging agent to be investigated for direct visualization of [alpha-synuclein] and TDP-43 biomarkers in the retina, an accessible part of the CNS that can be imaged non-invasively,” Stella Sarraf, PhD, Amydis’ CEO and founder, said in a company press release.
The Phase 1/2 trial, dubbed PROBE (NCT05542576), aims to enroll up to 36 adults with Parkinson’s or ALS at two sites in Southern California. Recruitment is currently ongoing at the Eye Research Foundation, in Newport Beach, and is expected to open at the California Eye Specialists, in Pasadena. Contact information is available for those interested in learning more.
Participants will receive a single injection of AMDX-2011P directly into the bloodstream, at one of four doses (25, 50, 100, or 200 mg).
The study’s main goal is assessing the tracer’s safety and tolerability, as determined by the rate and nature of adverse events over one week after the single dose.
Secondary goals include the detection of alpha-synuclein or TDP-43 protein deposits in the retina in corresponding patients and AMDX-2011P’s pharmacokinetics, which refers to the tracer’s movement into, through, and out of the body.
AMDX-2011P is an investigational agent that may assist in diagnosing and monitoring a condition; Amydis notes that no tests to detect such protein deposits have been approved. AMDX-2011P is not intended to cure or treat Parkinson’s or ALS.
“To my knowledge, exploring a diagnosis … through the eye is a novel and unique approach which may help us identify people at risk earlier in the disease and potentially help with drug development,” said Merit Cudkowicz, chief of neurology at Massachusetts General Hospital and a member of the PROBE trial’s safety and monitoring committee.