New PET tracer imaging tech could help track nerve fiber loss in MS
Study: It may provide means to select candidates for treatment, monitoring
A new positron emission tomography (PET) tracer may help determine the extent of nerve fiber loss in multiple sclerosis (MS) lesions, something that can’t be identified with conventional MRI imaging, according to a new study.
Researchers think the new imaging tech could help track the efficacy of experimental therapies that aim to promote myelin repair.
The study, “First evaluation in multiple sclerosis using PET tracer [18F]3F4AP demonstrates heterogeneous binding across lesions,” was published in the European Journal of Nuclear Medicine and Molecular Imaging.
PET tracer highlights axons that have lost myelin
In MS, inflammation in the brain causes damage to the myelin sheath, which is a fatty covering that wraps around axons, or nerve fibers, and helps nerves to send electrical signals. The loss of myelin leads to axonal dysfunction and damage, disrupting normal nerve signaling and ultimately driving MS symptoms.
MRI scans are a standard type of imaging technology used to track disease activity in MS. On MRI scans, areas where myelin has been damaged and lost are visible as spots called lesions. A drawback of MRI scans, however, is that they cannot differentiate lesions with intact axons versus lesions where axons have been lost.
MRI images the body’s structures by detecting signals from water molecules. PET scans are an imaging technology that generally use tracers, which are basically molecular dyes that stick to specific biological structures and cause them to light up on the scans.
Studies in animal models have indicated that a novel tracer called [18F]3F4AP can highlight axons that are intact but have lost myelin. The tracer specifically binds to certain potassium channels that are normally hidden under intact myelin, but exposed on nerve fibers when myelin is lost.
It was developed by radioactively labeling the active ingredient Ampyra (dalfampridine), a therapy approved to improve walking ability in people with MS.
Results in humans largely consistent with those in preclinical animal studies
An ongoing Phase 1 study (NCT04699747) is assessing whether the tracer can be used to detect changes in myelin. The study is a joint effort between Quantum Biopharma and Massachusetts General Hospital (MGH). Quantum hopes the tracer will be able to show in a follow-up trial that its drug Lucid-MS can prevent demyelination and promote myelin repair.
“The ongoing collaborative study with MGH seeks to further evaluate the imaging agent and its potential to demonstrate the effectiveness of drugs, such as Lucid-21-302 (Lucid-MS), that can protect the myelin sheath in MS,” Andrzej Chruscinski, MD, PhD, vice president of scientific and clinical affairs at Quantum, said in a company press release.
The researchers shared results from three people with MS and three people without the disease who were enrolled in a Phase 1 study. Their goal was to determine if the tracer could distinguish between different levels of myelin and axonal loss.
“In this study, we first evaluated the robustness of [18F]3F4AP as a brain imaging agent in humans, including in people with MS,” the scientists wrote.
Participants underwent standard MRI scans, as well as PET imaging with the novel tracer. Tracer uptake in the brain was generally higher in MS patients, which was expected given that the tracer is thought to highlight myelin loss. The tracer also showed good consistency from person to person, the researchers said.
“The relatively low variability across subjects suggests this tracer meets the requirements to become a robust biomarker,” the researchers wrote, noting that “the results in humans were largely consistent with prior results in preclinical animal studies.”
Among the MS patients, some lesions showed higher than normal levels of the tracer on PET scans, but other lesions had lower than normal tracer binding, and still others had normal tracer binding.
The published study shows that the PET tracer is highly promising as a biomarker to detect and monitor lesions in people with MS.
The researchers proposed that lesions with high signals likely represent areas with myelin loss, but where axons are largely intact, whereas low signals indicate axons that have been lost. Normal signals, meanwhile, may indicate relatively little myelin loss or some myelin repair.
“Perhaps the most remarkable finding of our study, which, if confirmed, could change the way we understand and monitor the heterogeneity of lesions in MS, was the different binding of the tracer across MS lesions,” the researchers wrote.
The scientists emphasized that further studies are needed to validate the results and confirm if their interpretation is correct. If it’s true that this tracer can distinguish lesions with and without axon damage, then it “may provide a means to select candidates for remyelinating treatments and monitoring for the effect of those treatments,” the researchers wrote.
Quantum is now working to launch a Phase 2 trial of the therapy in people with MS. The company expects to file for clearance of the trial later this year.
“The published study shows that the PET tracer is highly promising as a biomarker to detect and monitor lesions in people with MS,” Chruscinski said.
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