Earlier detection has the potential to change how ALS and other neurodegenerative diseases are diagnosed, studied, and ultimately treated.
US biotech Amydis has secured a $2.5 million Phase 2 grant from the National Institute on Aging to advance its development of imaging technologies that detect disease biomarkers through the eye. The funding is specifically intended to support the San Diego-based company’s efforts to detect a key protein linked to amyotrophic lateral sclerosis (ALS) and related neurodegenerative conditions.
Amydis’ approach builds on a growing scientific understanding that the eye can provide insights into systemic disease. The retina contains cells and structures connected to the central nervous system, making it possible to observe biological changes associated with conditions affecting the brain. The company’s technology is based on small-molecule fluorophores engineered to bind to specific protein deposits, allowing clinicians to visualize molecular biomarkers that would otherwise remain invisible using standard imaging.
ALS diagnosis typically relies on excluding other conditions, a process that can take months or even years while the disease continues to progress. Amydis is developing a non-invasive diagnostic approach for identifying a molecular hallmark found in the vast majority of ALS cases: a protein known as TDP-43.
“Currently, it takes 9-12 months to receive a diagnosis of ALS, delaying precious time for people to seek therapeutic intervention,” Amydis founder and CEO Dr Stella Sarraf told us. “Unfortunately, there is no test to directly detect the molecular biomarker TDP-43 in living people, even though it is present in over 97% of people with ALS.”
Amydis is attempting to address that gap by creating a fluorescent ocular tracer designed to reveal TDP-43 deposits in the retina during a routine eye examination. The tracer binds selectively to disease-related proteins and produce a signal detectable with standard ophthalmic imaging equipment commonly used in eye care clinics. If successful, the approach could enable clinicians to detect molecular signs of neurodegeneration through a simple eye test integrated into everyday eye care visits.
The Phase 2 award follows the Amydis’ earlier Phase 1 NIH grant, which supported preliminary studies demonstrating that its fluorescent tracer could detect TDP-43 deposits in retinal tissue collected from deceased patients with ALS, frontotemporal dementia and limbic-predominant age-related TDP-43 encephalopathy (LATE), a neurodegenerative condition that affects memory in older adults.
“For the first time, we have shown that this biomarker can be visualized in retinal tissue with our novel tracer, qualify the eye as a potential means to diagnose ALS,” said Sarraf. “This second NIH grant award will allow us to further map where TDP-43 is located in ALS retinal tissues as well as across other TDP-43-related diseases like FTD and LATE, and use that information to guide as we prepare for human clinical studies.”
The new grant will allow Amydis to expand its analysis of retinal tissue samples in order to further characterize the distribution of TDP-43 in the eye. Researchers plan to apply AI tools to examine patterns of protein deposition, with the aim of identifying disease-specific molecular signatures. Such distinctions could help physicians differentiate between related neurodegenerative disorders and potentially guide treatment strategies in the future.
“Prodromal detection of TDP-43 in people with ALS would be a step forward for our field,” said Dr Merit Cudkowicz, exec director of the Mass General Brigham Neuroscience Institute. “A molecular biomarker test to detect TDP43 in the eye has the potential to facilitate clinical trial design and drug targeting, as well as accelerate patient enrollment in clinical trials providing earlier access to promising investigational therapies.”
