The uses of ultrasensitive technology in guiding diagnostics for MS

Aug. 15, 2017

According to the Multiple Sclerosis (MS) Foundation, an estimated 400,000 people in the United States and about 2.5 million people worldwide suffer from MS. About 200 new cases are diagnosed each week in the United States. MS is the most widespread disabling neurological condition of young adults around the world, and researchers today have little understanding about what causes it. Neurodegeneration plays a key role in MS, contributing to long-term disability in patients. The prognosis is complicated by disease mechanisms that can only be clearly understood through the analysis of biomarkers specific to pathobiology of the underlying process.

The role of ultrasensitive technology

MS is an autoimmune disease that causes the immune system to attack and damage the myelin sheath of nerve cells. Although the precise cause of MS is unknown, many researchers believe that there is a genetic component to the disease. In order to better understand the impact the disease has on neural damage, clinical labs are looking at protein biomarkers in the blood. The ability to closely monitor and track neural damage in MS patients provides clinical lab researchers with a potential pathway to better understanding the disease, which could ultimately enable better treatment and earlier diagnosis in patients.

In order to track and monitor proteins in the blood, researchers use ultrasensitive biomarker analysis technologies that can detect miniscule amounts of proteins in the serum, plasma, and cerebrospinal fluid. Research shows that a highly sensitive and reliable measurement platform can be used to determine the blood-based, early changes of bioactive molecules for neurodegenerative disease, as well provide targets for developing therapeutic strategies.

To enable the detection of miniscule proteins in the blood, clinical lab researchers use a digital ultrasensitive technique that is substantially more sensitive than conventional, analog immunoassay technologies. The digital nature of the technology provides the ability to trap single molecules in femtoliter-sized (10-15 liters) wells, allowing for a “digital” readout of each individual bead to determine if it is bound to the target analyte or not.

The role of biomarkers

By understanding the role of protein biomarkers in the blood of patients who suffer from MS, clinical labs are able to detect patients who may have MS earlier in the disease pathway, even before symptoms present. Researchers and doctors can also use protein biomarkers to monitor and gauge the effectiveness of therapeutic interventions.

In order to objectively and correctly detect, measure and guide therapeutics for patients, researchers need to use an ultrasensitive technology that can analyze promising biomarkers for MS, including neurofilament light, IFN-γ-inducible protein 10, Interleukin 5 and Interleukin-12p70.

Detecting and monitoring MS

Researchers have been exploring the role of neurofilament light chains (NfL) as it relates to MS, and recent studies looking at NfL have shown it to be a clinically meaningful blood biomarker to monitor tissue damage and the effects of therapies in MS. NfL is a 68 kDa cytoskeletal intermediate filament protein that is expressed in neurons.

Another assay which researchers are exploring is IFN-γ-inducible protein 10 (IP-10). IP- 10 is constitutively expressed at low levels in thymic, splenic, and lymph node stroma. Expression of IP-10 is seen in many Th1-type human inflammatory diseases, including skin diseases (e.g., psoriasis), MS, atherosclerosis, rheumatoid arthritis, transplant rejection, and inflammatory bowel disease. Elevated levels of IP-10 protein have been found in the cerebrospinal fluid in patients with viral meningitis and MS.

Researchers from the University of Mississippi Medical Center and the German Center for Neurodegenerative Disease used an ultra-sensitive, single molecule digital analyzer platform with the ability to measure the molecules in plasma and tissue homogenates at serial pg/ml to fg/ml in a very reliable manner—R square values are as high as 99 in serial dilution tests. They’ve now successfully established tests for several cytokines and also for a neurosteroid allopregnanolone in human plasma samples. Further spike and recovery experiments in diluted samples help them to accurately measure the spiked samples in calibrator into those diluted brain samples (recovery 70 percent to 93 percent). The high sensitivity also indicates that these molecules can be measured in a small size quantity/volume (less than 200μ) of samples. Therefore, the highly sensitive and reliable measurement platform have potential to be used to determine the blood-based, early changes of bioactive molecules for neurodegenerative disease, such as MS. The results can also provide targets for developing therapeutic strategies for these neurodegenerative diseases.

Putting research into action

By using ultrasensitive assays, researchers have the opportunity to advance the detection of MS and also use these biomarkers as a guide to show how therapeutics are working in patients. The advancements of ultrasensitive technologies using assays such as NfL and IP-10 have been critical in advancing our understanding of neurogenerative diseases and the development of effective therapeutics. With further research using ultrasensitive technologies, researchers can advance the knowledge and understanding of neurodegenerative diseases like MS.

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