1st patient imaged in clinical trial of new PET tracer for MS
Tracer aims to detect changes in myelin loss
The first person with multiple sclerosis (MS) has been successfully imaged in a clinical trial evaluating a new positron emission tomography (PET) tracer designed to detect changes in myelin loss, or demyelination.
The Phase 1 study (NCT04699747), a joint effort between Quantum Biopharma and Massachusetts General Hospital, aims to recruit about 60 adults, including healthy individuals as well as MS patients.
The trial will first assess the safety and pharmacological profile of the PET tracer, named [18F]3F4AP. The study will also evaluate the tracer’s ability to monitor demyelination, the loss of the protective myelin sheath around nerve fibers, in the central nervous system (brain and spinal cord), which is a hallmark of MS. This could help assess patient responses to treatment.
“We are excited that the study has started and that we are learning more about the potential of this novel PET biomarker to directly visualize and measure demyelinated [nerve fibers] in the central nervous system,” Andrzej Chruscinski, MD, PhD, vice president of scientific and clinical affairs at Quantum, said in a company press release.
Should findings from the Phase 1 trial be positive, [18F]3F4AP may help to assess MS patients’ responses to Lucid-MS, Quantum’s experimental oral therapy to prevent demyelination and promote myelin repair.
PET tracer imaging ‘holds promise as a biomarker’
A Phase 1 trial (NCT06595706) showed the therapy, also known as Lucid-21-302, was generally safe and well tolerated in healthy adults, and the company is planning a Phase 2 study to test Lucid-MS in people with MS.
“PET imaging with [18F]3F4AP holds promise as a biomarker to measure the efficacy of drugs that can protect the myelin sheath in MS such as Lucid-21-302 (Lucid-MS),” Chruscinski said.
Standard imaging methods like MRI, while effective in detecting neuronal damage, lack specificity for monitoring demyelination.
[18F]3F4AP binds to potassium channels, Kv1.1 and Kv1.2, proteins that are normally hidden under intact myelin but exposed on nerve fibers when myelin is lost. The tracer was developed by radioactively labeling the active ingredient of Ampyra (dalfampridine), a therapy approved to improve walking ability in people with MS. Like [18F]3F4AP, the drug also targets these potassium channels.
Given shortly before a PET scan, [18F]3F4AP travels through the bloodstream, crosses the blood-brain barrier — a membrane that protects the brain and spinal cord from potential threats — and binds to the exposed proteins in demyelinated areas. The radioactive signal emitted by the tracer is then captured by the PET scanner, producing detailed images of myelin loss.
The tracer showed a good safety profile in a small, first-in-human Phase 1 study (NCT04710550).
In the ongoing Phase 1 trial, serial PET scans using [18F]3F4AP will be performed alongside MRI scans to compare the tracer’s binding patterns with MRI-detected lesions, assessing its accuracy in tracking demyelination.
The combined scanner “improves the patient experience by reducing the time needed to complete both scans,” Quantum said.
“By employing the latest technologies, we hope to learn more about how [18F]3F4AP PET can enhance MRI for monitoring demyelination and, by doing so, facilitate the development of novel treatments for people with MS,” said Pedro Brugarolas, PhD, assistant professor at Harvard Medical School and the trial’s principal investigator.
The study is expected to end late next year.
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