Researchers have achieved a major advance by creating the first imaging tool capable of directly visualizing myelin damage in multiple sclerosis (MS). This breakthrough could enable earlier diagnosis, more accurate monitoring of disease progression, and better assessment of treatment responses.
Scientists at Case Western Reserve University School of Medicine have developed a novel molecular probe for detection with positron emission tomography (PET). The new myelin-directed molecular marker, called MeDAS, provides the first non-invasive way to image myelin integrity across the entire spinal cord simultaneously, as reported in the Annals of Neurology.
“While MS originates with an abnormal immune response, the primary damage that produces symptoms is to the myelin sheaths in the central nervous system,” said Yanming Wang, PhD, the study’s senior author and associate professor of radiology at Case Western Reserve University School of Medicine. “Our discovery brings new hope to clinicians: an accurate diagnosis and prognosis could be achieved in hours rather than the months or years many patients currently face. The spinal cord’s small size and complex shape make direct molecular imaging of myelin especially challenging; this is the first method that images spinal cord myelin function at the molecular level.”
Multiple sclerosis is the most common acquired autoimmune disease of the central nervous system and affects millions worldwide. MS is defined by damage to myelin, the insulating membrane that surrounds nerve fibers. Loss of myelin compromises the ability of nerves to conduct electrical signals, which manifests as cognitive problems, loss of balance, weakness, and other neurological deficits. There is no cure at present; available therapies modify the disease course or symptoms but do not fully restore damaged nerve function.
MeDAS has potential value in several clinical and research areas. It can provide a quantitative, real-time assessment of myelin health, which could improve how clinicians diagnose MS and follow its progression. Current approaches such as behavioral testing and magnetic resonance imaging (MRI) can take months to correlate with symptoms, and MRI-detected lesions in the brain and spinal cord are not myelin-specific and often do not match a patient’s clinical status. A myelin-specific imaging marker that correlates with tissue pathology addresses a clear unmet need in MS care and clinical trials.
“This discovery opens the door to developing drugs that aim to restore nerve function rather than only controlling symptoms,” said Robert Miller, PhD, co-author of the study and vice president for research at Case Western Reserve, who also holds the Allen C. Holmes Professorship of Neurological Diseases. “A true cure for MS will require both effective remyelination therapies and reliable tools to measure whether those therapies actually repair myelin.”
For more than two decades, Miller’s laboratory has pursued therapies designed to repair myelin and restore neuronal function. Translating promising remyelination drugs from animal models into human clinical trials depends on having precise, objective measures of myelin repair; MeDAS aims to provide that capacity.
Developed in Wang’s laboratory, the MeDAS probe acts like a molecular homing device. Administered intravenously, it selectively binds to myelin in the central nervous system — including the brain, spinal cord, and optic nerves. The probe is labeled with a positron-emitting radioisotope that a PET scanner can detect, allowing clinicians and researchers to quantify the location and intensity of myelin binding. These signals are reconstructed into images that reveal areas of intact myelin and regions of demyelination. Such images support diagnosis, track disease activity over time, and enable evaluation of therapies intended to promote myelin repair.
“MeDAS is an indispensable tool for developing next-generation treatments for MS,” said Chunying Wu, PhD, the study’s first author and an instructor of radiology at Case Western Reserve. “Beyond multiple sclerosis, this platform technology could be applied to other disorders involving myelin damage, such as spinal cord injury and other demyelinating conditions.”
The research team has completed preclinical animal studies and has begun the regulatory process to initiate human trials, marking an important step toward clinical translation.
Notes about this multiple sclerosis research
This study received support from the Department of Defense (grant W81XWH-10-1-0842), the National Multiple Sclerosis Society (grant RG 4339-A-2), and the National Institutes of Health (grant R01 NS061837).
Contact: Jessica Studeny – Case Western Reserve University
Source: Case Western Reserve University press release
Image Source: Neuron diagram credited to Andrew c, public domain.
Original Research: Abstract for “Longitudinal positron emission tomography imaging for monitoring myelin repair in the spinal cord” by Chunying Wu, PhD; Junqing Zhu, BS; Jonathan Baeslack, BS; Anita Zaremba, BA; Jordan Hecker, BS; Janet Kraso, BS; Paul M. Matthews, MD, PhD; Robert H. Miller, PhD; and Yanming Wang, PhD, published in Annals of Neurology. Published online September 23, 2013. DOI: 10.1002/ana.23965