In-Focus: Multiple Sclerosis

Pearls from the Podium: 2017 ACTRIMS Forum

In February, MS specialists convened in Orlando for the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2017 Forum. This year’s meeting explored several research threads related to the etiology of MS and the factors influencing its progression. Here are several standout quotes from various presentations throughout the meeting.

“An epidemic of autoimmune disease over the last 70 years suggests that MS risk is not just genetics but also environment… Increased fat and salt intake over that time may be one environmental risk factor for autoimmune diseases.”

—David A. Hafler, MD

“Possible association of puberty and disease activity should be confirmed before making treatment recommendations…. The underlying biological processes of the link between puberty and MS are still to be determined.”

—Emmanuelle Waubant, MD, PhD

“MS-associated retrovirus (MSRV) expression parallels MS onset, behavior, and therapy outcome… In vivo MSRV in the CSF at MS onset is predictive of worst prognosis in the next 10 years.”

—Ninella Dolei, MD

“Emerging evidence indicates an important link between our microbial self, immune system, and brain health… Early data indicate differences in the microbiome of patients with MS, but more studies are necessary to strengthen our understanding of how the microbiome impacts MS.”

—Irah King, PhD

“Pediatric MS offers a unique opportunity to explore possible triggers or modifiers of the disease… Intriguing observations regarding the microbiota’s potential role in pediatric MS warrant further investigation.”

—Helen Tremlett, PhD

Interleukin-16 Gene Tied to MS Risk

Single-nucleotide polymorphisms (SNPs) in the IL-16 gene may lead to altered cytokine expression or biological activity and may modulate an individual’s risk for MS, according to new findings. Researchers analyzed three SNPs of IL-16 in 250 MS patients and 400 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The IL-16 rs4072111C/T genotype and allele frequencies showed significant differences between MS patients and controls, while differences were also found in allele and genotype frequencies of rs11556218 G/T between two groups. Additionally, mean serum levels of IL-16 in MS patients were significantly higher in MS patients compared to healthy controls. The authors concluded that the rs11556218T/G and rs4072111C/T polymorphisms of IL-16 gene are associated increased risk of MS and may contribute to susceptibility to MS.

— Immunol Invest. 2017 Feb 2:1-9.

HDIT and Autologous Hematopoietic Cell Transplantation Prove Effective in the Long-Term

High-dose immunosuppressive therapy (HDIT) and autologous hematopoietic cell transplantation (HCT) could possibly induce long-term sustained remission of active relapsing MS without maintenance therapy for as long as five years, according results from the HALT-MS phase 2 trial. In 24 participants who underwent HDIT/HCT over a five year-period, progression free survival was 91.3 percent, clinical relapse-free survival was 86.9 percent, and MRI activity-free survival was 86.3 percent. Adverse events were consistent with expected toxicities, while there were no significant late neurologic adverse effects.

—Neurology, February 1, 2017

Kynurenine Pathway Offers Insight into MS Progression

Abnormalities in the kynurenine pathway (KP) may be associated with the switch from early-mild stage MS to debilitating progressive forms of MS, according to a new study. To gain insights into the links between inflammation, the KP and multiple sclerosis (MS) pathogenesis, researchers investigated the KP metabolomics profile of MS patients.

They found aberrant levels of two key KP metabolites, kynurenic acid (KA) and quinolinic acid (QA). “The balance between these metabolites is important as it determines overall excitotoxic activity at the N-methyl-D-Aspartate (NMDA) receptor,” the authors wrote. They also identified that serum KP metabolic signatures in patients can discriminate clinical MS subtypes with high sensitivity and specificity. A C5.0 Decision Tree classification model discriminated the clinical subtypes of MS with a sensitivity of 91 percent, which was maintained at 85 percent in another independent cohort.

—Scientific Reports, Article number: 41473 (2017)