A new diagnostic tool being developed to identify MS in the early stages has continued to perform well in a series of clinical studies and the process of validating these results in a prospective, multi-site clinical trial has begun.
MSPrecise™ is a sequencing assay that analyzes changes in key genes involved in the adaptive immune system of people being evaluated for MS. In clinical studies it has outperformed the specificity of the current standard of care for cerebral spinal fluid (CSF) analysis by almost two to one with no loss of sensitivity, according to product developer DioGenix.
MSPrecise measures DNA mutations found in rearranged immunoglobin genes in B cells isolated from cerebrospinal fluid (CSF). These mutations are a result of the adaptive immune system's response to a perceived challenge to the patient. The changes in the B cell DNA correspond to the production of diverse antibody libraries aimed at fighting the perceived foreign invader.
The specific mutational changes observed in people with MS are different from those observed in people with similar neurological diseases because the antigens recognized by the antibodies are different, results from DioGenix's clinical studies suggest.
The current diagnostic standard of care for MS includes CSF analysis using the oligoclonal banding test, which detects immunoglobin G proteins that indicate an immune response within the CNS. Because the oligoclonal banding test yields a high rate of false positive results, confident diagnosis also requires a comprehensive set of clinical tests including magnetic resonance imaging and, in certain cases, visual evoked potentials. Due to the variability of symptoms between patients and the lack of a definitive test, it has been estimated that the misdiagnosis rate for MS is higher than any other immune-mediated neurological disease, DioGenix reports.
MSPrecise would augment clinicians' current standard of care for the diagnosis of MS, providing measurement of changes in B cell DNA as compared to merely the presence of immunoglobin G proteins in the CSF. This novel method of measuring changes in human immunity during the early stages of the disease may also be able to discern individuals whose disease is more progressive and requires more aggressive treatment.
In a recently completed study, DioGenix analyzed CSF samples that were retrospectively and prospectively collected from people with MS and other neurological diseases, as well as healthy controls. CSF from two cohorts of approximately 40 to 45 patients each were compared; the first cohort included people with a confirmed diagnosis of relapsing remitting MS, and the other cohort consisted of people with other neurological diseases that mimic the presentation of MS and healthy controls. Subjects with MS had MSPrecise scores that were statistically significantly higher compared to both healthy controls and patients with other neurological diseases.
"MSPrecise quantifies specific molecular changes in CSF-derived B cells and results generated to date indicate that it is more accurate than oligoclonal banding. The DioGenix assay bridges the divide between immunology research and bedside care using cutting-edge technology," said Dr. Michael Racke, Professor and Chairman of Neurology at The Ohio State University. "This represents an exciting advance in our efforts to more accurately diagnosis patients with multiple sclerosis and it is based on clinically relevant biomarkers of immune system response."