Repurposed ALS drug presents a noninvasive diagnostic approach for neurodegeneration

Neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease, are primarily diagnosed by physical symptoms that occur when treatment is often too late to be effective. Better diagnostic approaches are needed to treat patients with these diseases more effectively.

Positron emission tomography (PET) is a nuclear imaging technique used to visualize conditions such as cancer. In a study published in Nature Biomedical Engineering, St. Jude scientists derivatized the drug edaravone, an antioxidant used to treat ALS, to enhance the detection of neurological disease using PET imaging.

As an antioxidant, edaravone works by countering the effects of reactive oxygen and nitrogen species (RONS), a group of chemically reactive molecules vital to cell signaling and growth. Accumulation of RONS can cause oxidative stress, which is associated with neurological conditions such as stroke and neurodegeneration. Detecting oxidative stress through a noninvasive imaging technique could potentially shift diagnosing and treating neurodegenerative conditions much earlier, when such care is more beneficial.

Its natural interaction with RONS led the corresponding author, Kiel Neumann, PhD, Department of Radiology, to hypothesize that edaravone could be repurposed to enhance imaging efforts. Neumann’s team radiolabeled edaravone, replacing atoms in the molecule with radioisotopes that allowed him to track the movement and breakdown of the drug. After administration, the radiolabeled drug releases subatomic particles called positrons that emit signals detectable by a PET scan. The areas where the drug accumulates the most emit the strongest signal, indicating where oxidative stress buildup is highest. 

“The goal in imaging is to promote contrast, so we want something that engages with its target rapidly but then also quickly clears so you can see your target right away,” said Neumann. “Uniquely, when the drug reacts with oxidative stress, it undergoes a massive structural and polarity change, which keeps it in the cell longer and promotes contrast.”

Edaravone’s excellent ability to bind RONS in tiny doses means it is ideally suited for PET imaging, while it can still be used as an antioxidant treatment at standard doses — a potential diagnostic and treatment combo. With this technique, researchers can detect oxidative stress, offering a clear path to establishing earlier therapeutic windows for neurological conditions.

“Ultimately, our goal is to use this to impact clinical care,” said Neumann. “Therapeutic intervention using this technology for clinical disease management is the future.”