BALTIMORE—A University of Maryland research team has discovered a biomarker that can determine whether a patients has multiple sclerosis or is relapsing, thanks to VA funding. Now two VA organizations focused on technology transfer are working to bring the biomarker to market.
Approximately one million people in the United States have MS, among them about 60,000 veterans. In MS, the immune system attacks healthy tissue in the central nervous system and gradually destroys the myelin sheath that covers and protects the nerves.
Damage to the sheath disrupts electrical signaling between the brain and other parts of the body. That can cause a variety of symptoms, including: visual disruptions; muscle weakness; problems with gait, balance and coordination; numbness and pain; tremors; speech impediments; hearing loss; paralysis; and cognitive impairment.
Individuals with the most common form of the disease, relapsing-remitting multiple sclerosis, can go months or years between relapses. In patients with progressive multiple sclerosis, symptoms continue to worsen.
“Currently the diagnosis of the relapses is based on clinical findings (new symptoms which persists more than 24 hours) and by using brain or spine magnetic resonance imaging (MRI) to find active lesions which are also called gadolinium enhancing lesions,” said lead researcher Horea Rus, MD, PhD, professor of neurology at the University of Maryland.
Other tests used for diagnosis and disease monitoring include visual evoked potential testing and painful cerebrospinal fluid testing.
Brain MRIs are expensive and frequently require preapproval from insurance companies, delaying their use and the time to diagnosis or identification of a relapse. In addition, patients with claustrophobia require sedation for the exam and sometimes refuse to have an MRI at all, Rus explained.
Symptoms alone cannot reliably indicate either development of MS or a relapse, he noted, and patients who have no symptoms may still be experiencing disease progression. Even an MRI can fail to detect a relapse or progression in patients with “smoldering” MS, making a more reliable method important for monitoring disease progression and response to therapy.
Proteins Indicate Relapse and Response
Rus and Cosmin Tegla, MD, of the division of hematology and oncology at New York University Langone Health received a patent for a blood-based biomarker in May. The new biomarker analyzes proteins in a patient’s blood, including Sirtuin 1, Response Gene to Complement-32, Fas ligand and interleukin21.
“The biomarker will be a replacement for the brain MRI,” Rus told U.S. Medicine, and it will be “far less expensive.”
The researchers previously published studies of 15 patients over two years that demonstrated the ability of the proteins to identify patients experiencing a relapse and response to therapy.
They found that SIRT1 messenger RNA is lower in the peripheral blood mononuclear cells of patients with multiple sclerosis who are experiencing a relapse than in those with stable disease. In addition, patients who responded to treatment with glatiramer acetate, a common therapy for MS, had higher SIRT1 mRNA than nonresponders.1 The study defined nonresponders as participants who had two or more relapses after starting treatment with glatiramer acetate. Overall, SIRT1 mRNA had a 70% probability of accurately predicting response to the therapy.
The Maryland team also found that expression of RGC-32 and FAsL declined and IL-21 increased during acute relapses. Participants who responded to glatiramer acetate showed increased expression of both RGC-32 and FasL and reduced expression of IL-21. RGC-32 had a 90% probability of accurately detecting a relapse and 85% accurate for detecting response to glatiramer acetate, while FasL was 99% and 90% and IL-21 75% and 85% accurate for the two statuses, respectively.
“The test can be used to monitor response to therapy and distinguish between responders and nonresponders to MS therapy based on its levels in the blood,” Rus explained. “If a patient has a relapse, then he will need to be switched from the MS therapy he is taking to a new one.”
While Rus and Tegla received the patent, ”both inventors assigned their patent rights to the University of Maryland-Baltimore, which is the patent’s co-assignee with the VA. But then the university assigned all of its rights to the VA. All that means is that ownership is consolidated now under the VA,” TechLink Senior Technology Manager Gary Bloomer told U.S. Medicine.
“Our marketing on the MS biomarker technology is in progress and is aimed at helping the VA find the best industry partner to take the technology to market, and then to help that company identify the opportunity and assist them through evaluation and licensing,” he added.
TechLink’s licensing experts and business advocates “help private companies evaluate and license VA inventions, sort of like a matchmaker,” Bloomer said.
TechLink and the VA Technology Transfer program have been helping companies take VA technology to market for the benefit of both veterans and the general public since 1999.
The two groups “work collaboratively to bring the medical industry’s attention to the scientific achievements of the VA and VA-funded researchers who are consistently inventing novel medical devices, detection technologies and therapies,” Bloomer added. “The VA’s patent portfolio contains many opportunities for companies to expand in the healthcare field.”
Hewes D, Tatomir A, Kruszewski AM, Rao G, Tegla CA, Ciriello J, Nguyen V, Royal W 3rd, Bever C, Rus V, Rus H. SIRT1 as a potential biomarker of response to treatment with glatiramer acetate in multiple sclerosis. Exp Mol Pathol. 2017 Apr;102(2):191-197.
Kruszewski AM, Rao G, Tatomir A, Hewes D, Tegla CA, Cudrici CD, Nguyen V, Royal W 3rd, Bever CT Jr, Rus V, Rus H. RGC-32 as a potential biomarker of relapse and response to treatment with glatiramer acetate in multiple sclerosis. Exp Mol Pathol. 2015 Dec;99(3):498-505.
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