disease progression

The RhoE protein has been identified as being important for axons’  myelination and extension in the central nervous system, two processes that go awry in diseases like multiple sclerosis (MS). The findings stem from Pilar Madrigal’s doctoral thesis, “Role of the small GTPase RhoE in myelination and axonal tracts development.”…

Life never lets me forget its fragility. Sometimes my challenges seem like mountains to be scaled. Adversity has become the elephant in the room; it is ever present even when I refuse to acknowledge it. A few weeks ago, I faced what could potentially have been a medical crisis.

Genetic variants that enhance the activity of the NLRP3 inflammasome or the interleukin-1 beta cytokine are linked to higher severity and progression of multiple sclerosis, a study suggests. Previous studies with mouse models of MS have shown that a complex of innate immune system receptors and sensors, known as the inflammasome, is likely a player promoting the immune system’s attack on the central nervous system in MS and, consequently, the loss of myelin. Follow-up studies showed that people carrying mutations that enhance the function of the NLRP3 inflammasome — one of the three components of the inflammasome complex — had a worse prognosis, once again supporting the role of the inflammasome in MS. Once activated, the inflammasome triggers an enzyme called caspase-1 that promotes the production of two very powerful proinflammatory cytokines called interleukin (IL)-1 beta and IL-18. To further evaluate the role of the inflammasome in MS, a team led by researchers at the Universidade de Sao Paulo in Brazil analyzed the genetic sequence of five inflammasome genes — NLRP1, NLRP3, NLRC4, IL-1 beta, and IL-18 — in blood samples retrieved from 264 patients diagnosed with MS or other demyelinating diseases. They also analyzed 233 healthy individuals used as controls. The team specifically looked at eight variations in certain nucleotides (the building blocks of DNA), called single nucleotide polymorphisms (SNPs). Previous studies reported a link between SNPs in inflammasome-related genes and certain forms of MS. Results showed that SNPs associated with low serum levels of IL-18 were significantly less frequent in MS patients than in controls. In contrast, variants that enhance the function of NLRP3 and IL-1 beta were associated with severity and progression of MS, as measured by the Expanded Disability Status Scale. These results suggest that the "activation of NLRP3 inflammasome could represent a risk factor for MS clinical presentation,” the researchers wrote. A particular variant in the NLRC4 gene was less frequent in patients whose disease progressed rapidly compared with those who had a slower disease, an intriguing observation, according to researchers, suggestive of a “protection effect of this variant against a bad prognosis.” Carriers of this variant also responded better to treatment with interferon-beta. Regarding MS type, the genetic variant that promotes the function of the IL-1 beta gene was significantly more frequent in progressive forms of MS than in relapsing-remitting MS, strengthening once again the negative effects of IL-1 beta in the disease. An analysis of inflammasome activity in blood monocytes, a group of immune cells, showed that the inflammasome is permanently activated in MS compared with healthy controls. "This study emphasizes that a constitutive activation of NLRP3 inflammasome, principally through IL-1 beta production, represents a risk factor for both the development of MS and the progression to severe forms of the disease. On the other hand, low IL-18 production and/or NLRC4 activation were beneficial for MS patients,” the team concluded.

“If I were you two, I think I’d plan for the worst,” Amy, my physiatrist, said to my wife and me as we sat in the examination room. It was just after 11 a.m. on Friday, Jan. 18. January has become one of two pivotal months in terms of…

Fatigue is more prevalent among patients with progressive multiple sclerosis (MS), according to a study that surveyed patients on fatigue and factors related to it. In addition, increased fatigue severity correlated with greater physical, cognitive, and psychological impairment, although the strength of this link was largely the same…

Autologous hematopoietic stem cell transplant is better than disease-modifying therapies (DMT) at reducing the risk of disease progression in patients with relapsing-remitting multiple sclerosis (RRMS), results from the MIST clinical trial show. The study “Effect of Nonmyeloablative Hematopoietic Stem Cell Transplantation vs Continued Disease-Modifying Therapy on Disease Progression…

A Phase 3 clinical trial intending to confirm the potential of MD1003, a high-dose biotin, in treating progressive multiple sclerosis (MS) patients is completely enrolled, MedDay Pharmaceuticals, the investigational therapy’s developer, announced. The randomized, double-blind, and placebo-controlled study (NCT02936037), called SPI2, follows the previous Phase 3 trial (NCT02220933),…

When I was diagnosed in 2010 with primary progressive multiple sclerosis (PPMS), I didn’t know what to expect. It quickly became apparent that my doctors didn’t know, either. I’m sure they could have given me some scenarios of what my future might be…