|Project outline

MUSE – Multiple Sclerosis Biomarker Evaluation

Objective:
Development and Validation of an NMR-based metabolic constellation that early indicates the transition of relapsing-remitting (RRMS) to secondary progressive multiple sclerosis (SPMS). 

“A serum-based test for early diagnosis of the RRMS-to-SPMS transition to allow timely therapy adjustment”
Dr. Eric Schiffer, Head of Clinical Development, numares AG

Multiple sclerosis (MS) is considered to be an immune-mediated disease in which the body’s own defence cells attack the central nervous system. MS involves inflammatory and neurodegenerative processes that damage the insulating myelin sheaths of nerve fibers and the nerve cells themselves.  While about 10-15% of patients begin the disease with primary progressive MS (PPMS) showing continuously worsening of symptoms from disease onset, the majority of patients are initially diagnosed with relapsing-remitting MS (RRMS) [1,2]. In RRMS, patients experience attacks of neurological symptoms (relapses) followed by periods of complete or partial remission. Most RRMS patients will eventually transition to a secondary progressive course (SPMS) with continuous worsening of symptoms and accumulation of disability. The RRMS-to-SPMS transition requires a change in therapy as most MS medications are not effective in SPMS [3].  Currently, there is no diagnostic test for SPMS and clinical diagnosis of SPMS transition is difficult and time-consuming, as it requires retrospective evaluation of neurological exams and results from magnetic resonance imaging (MRI) of the brain of the last 12 months [1]. A diagnostic test that reliably identifies patients at early transition from RRMS to SPMS would improve management and long-term outcome of MS patients.

Study design:
Two-center, prospective, observational study

Material:
Serum samples from patients with RRMS or SPMS

Reference standard: 
Brain MRI in combination with retrospective evaluation of disease course and disability in neurological exams

Approach: 
University of Oxford and numares started a joint development program to develop metabolomics-based diagnostics tests in multiple sclerosis. In previous work, University of Oxford has discovered metabolic biomarkers for discriminating RRMS from SPMS patients using nuclear magnetic resonance (NMR)-based analysis of blood samples [4]. Oxford University and numares are currently conducting a prospective observational study to validate the identified biomarkers and combine them to a metabolic constellation that reliably indicates early transition from RRMS to SPMS. numares provides its Magnetic Group Signaling (MGS®) technology and NMR-based AXINON® IVD system to translate the biomarker constellation into an in vitro-diagnostic (IVD) test.

Success:
In 2017, Oxford University and numares initiated a prospective observational study for validation of previous work. 

References:
1.    Lublin, F.D., et al., Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology, 2014. 83(3): p. 278-86.
2.    Multiple Sclerosis Society. Types of MS. www.mssociety.org.uk/what-is-ms/types-of-ms
3.    Shirani A, Okuda DT, Stuve O. Therapeutic advances and future prospects in progressive forms of multiple sclerosis. Neurotherapeutics 2016; 13: 58–69.
4.    Dickens, AM, et al. A type 2 biomarker separates relapsing-remitting from secondary progressive multiple sclerosis. Neurology 2014. 83:1492-9

numares’ products are not yet available for sale within the United States; they have not yet been approved or cleared by the U.S. Food and Drug Administration.