Quantum joins team to study PET tracer demyelination tracking
Company to work with Mass General scientists on MS response
Quantum Biopharma is partnering with researchers at Massachusetts General Hospital in Boston on a clinical study to test a positron emission tomography (PET) tracer for monitoring changes in myelin content in people with multiple sclerosis (MS).
The Phase 1 study (NCT04699747) is recruiting healthy adults and people with progressive or relapsing-remitting MS, for a total of about 60 participants. The trial involves performing serial scans using the PET tracer [18F]3F4AP to determine how safe it is and establish its pharmacological profile.
The trial will also determine if the tracer can indeed be used to measure demyelination, or the loss of the myelin sheath that protects nerve fibers in the central nervous system — the brain and spinal cord — which may help to assess response to treatment.
“We are very excited about the potential of this novel PET biomarker to directly visualize and measure demyelination in the central nervous system,” Andrzej Chruscinski, MD, PhD, vice president of scientific and clinical affairs at Quantum, said in a company press release.
In MS, the immune system damages the myelin sheath around nerve fibers, causing symptoms. Quantum, which last year changed its name from FSD Pharma, is developing Lucid-MS, a patented oral small molecule designed to prevent demyelination and repair or replace any lost myelin. This should ease symptoms of MS caused by the loss of myelin.
PET tracer and myelin loss monitoring
Reliable methods for measuring myelin content in MS patients are limited, and new, more sensitive approaches are needed to monitor myelin loss and response to potential remyelinating therapies like Lucid-MS.
[18F]3F4AP is a radioactive form of the active ingredient in Ampyra (dalfampridine), which is approved to improve walking ability in MS. The medication is thought to bind to Kv1.1 and Kv1.2, two potassium channels found on the outside membrane of nerve fibers. These channels are normally covered by the myelin sheath, but when myelin is lost, Kv1.1 and Kv1.2 become exposed and may be detected with the tracer.
For PET, a small amount of [18F]3F4AP is injected into the bloodstream, and a scanner takes pictures of the body showing which brain regions are taking up the tracer. Those that have lost myelin will take up larger amounts of the tracer and appear brighter than surrounding tissues on the pictures.
“We are interested to study its potential as a biomarker to identify and monitor responders to remyelinating and neuroprotective treatments for MS and we are excited to undertake this important work with Quantum,” said Pedro Brugarolas, PhD, who’s leading the study at Massachusetts General Hospital. Brugarolas is an assistant professor Harvard Medical School.
In the study, serial PET scans will be performed along with MRI of the brain. The main goal is to check if [18F]3F4AP is safe and binds to its targets in the brain. Binding of the tracer will be compared with lesions drawn based on MRI scans to check if it can accurately monitor demyelination.
“We expect that this biomarker will be an important diagnostic tool,” Chruscinski said. “This is very relevant to our Lucid-MS clinical development program as Lucid-MS has been shown to protect the myelin sheath and prevent demyelination in animal models of MS.”
In a mouse model of MS, Lucid-MS eased MS motor symptoms after the disease had progressed to paralysis of the tail and hind limbs. Two Phase 1 studies in healthy adults showed that Lucid-MS is safe and well tolerated both as a single dose (NCT05821387) ranging from 50 mg to 300 mg and as multiple ascending doses (NCT06595706). Quantum is preparing for a Phase 2 study.
“We are glad to be part of this study and working with this team of scientists and physicians at Mass General in developing this PET tracer as a biomarker in MS,” said Zeeshan Saeed, founder and CEO of Quantum.
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