Amydis awarded $2.5M to develop diagnostic eye test for ALS
It could also help detect other neurdegenerative diseases
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- Amydis received $2.5M to develop an eye test aimed at earlier ALS diagnosis.
- The test detects toxic TDP-43 protein deposits, a hallmark of ALS, in the retina.
- This noninvasive method could improve clinical trials and treatment access for ALS.
Amydis has received a $2.5 million grant from the National Institutes of Health (NIH) to develop a simple eye test that could help detect toxic deposits of the TDP-43 protein — a hallmark of amyotrophic lateral sclerosis (ALS) and several other neurodegenerative diseases.
With the funding from the NIH’s National Institute on Aging, researchers will analyze retinal tissue — the light-sensitive layer at the back of the eye — from donated eyes and use artificial intelligence to identify disease-specific patterns of TDP-43 buildup.
The goal is to develop a noninvasive imaging approach that could detect these protein deposits earlier and help diagnose ALS and related conditions sooner.
“For patients and families facing ALS and related dementias, time is everything,” Stella Sarraf, PhD, founder and CEO of Amydis, said in a company press release. “We believe the eye represents a new frontier in neurodegenerative disease detection. Earlier detection has the potential to change how ALS and related diseases are diagnosed, studied, and ultimately treated.”
Majority of people with ALS have abnormalities in TDP-43 protein
Diagnosing ALS early can be difficult because there is no single test for detecting the disease. Instead, doctors usually reach a diagnosis only after multiple exams help rule out other diseases with similar symptoms.
The vast majority of people with ALS have abnormalities in a protein called TDP-43. This protein is normally found in the nucleus, which houses the cell’s DNA, where it regulates the activity of certain genes.
However, TDP-43 often acquires an abnormal shape in ALS and forms toxic deposits outside the nucleus, preventing it from carrying out its normal function. The loss of TDP-43 from the nucleus and the toxic protein clumps are believed to contribute to nerve cell death.
Despite TDP-43 deposits being a hallmark of ALS and other neurodegenerative conditions, there isn’t yet a test to detect TDP-43 in living patients.
Amydis is trying to address this issue by developing a noninvasive approach to detect TDP-43 in the retina. Some retinal cells connect directly to the brain, and changes in the retina often reflect changes in the brain.
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.
The company is developing a fluorescent ocular tracer, called AMDX-2011P, that binds to toxic deposits of abnormally folded proteins such as TDP-43 and makes them “light up” in imaging scans. This could allow doctors and researchers to measure those toxic clumps, perhaps offering a test for earlier diagnosis and better monitoring of neurodegenerative diseases such as ALS.
“Detection of TDP-43 in people with ALS [before symptoms begin] would be a step forward for our field,” said Merit Cudkowicz, MD, director of the Sean M. Healey & AMG Center for ALS at the Massachusetts General Hospital in Boston. “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.”
This Phase 2 grant builds on earlier research funded by a Phase 1 NIH grant, in which the company’s fluorescent tracer detected TDP-43 in retinal tissue from deceased patients with ALS and other conditions.
With that early funding, researchers examined the eyes of 16 deceased patients with ALS and nine healthy donors. Retinas were cut up and labeled with AMDX-2011P and antibodies against TDP-43, and data showed that AMDX-2011P bound strongly to the abnormal TDP-43 proteins.
Amydis has also sponsored a Phase 1 clinical trial called PROBE (NCT05542576), which tested AMDX-2011P in 13 adults with ALS or Parkinson’s disease. AMDX-2011P was given as a single infusion into the bloodstream at multiple doses and caused no serious side effects. The most common side effects included numbness or tingling, altered taste, and respiratory tract infection.
With the new funding, the company will continue its analysis of retinas from deceased patients and will apply artificial intelligence to define disease-specific patterns for ALS and other conditions that may allow researchers to distinguish these related disorders.
Amydis may also be planning a Phase 2 clinical trial at Mass General to continue studying its fluorescent tracer in people with ALS.
