NeuroImmunology

Gastroenterology & Endoscopy News Study Hints Gut Microbiome Plays A Role in Multiple Sclerosis Gastroenterology & Endoscopy News The study included untreated MS patients (n=19) as well as those treated with interferon β-1a (n=21), interferon β-1b...

Via Krishan Maggon

Highlights

 

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Ruth Arnon and Michael Sela profoundly influenced the development of a model system to test new therapies in multiple sclerosis.

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By measuring clinical, pathologic, and immunologic outcomes, the biological implications of new drugs could be elucidated.

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The pioneering research on Copaxone using the EAE model, paved the way for the discovery of other therapeutics in MS.

Via Krishan Maggon

RT @MSDForum: Daclizumab did well in phase 3 trials for #MS. Here's the story behind the story http://t.co/PFzsfHqKs1

 

 an analysis of samples from blood and cerebrospinal fluid suggests that daclizumab nudges the abnormal numbers of innate and adaptive immune cells in RRMS back to more normal physiological levels found in people without MS (Lin et al., 2014).

 

the therapeutic efficacy of daclizumab paralleled the expansion of a key target cell population, called CD56bright natural killer cells (CD56bright NK). That raised hopes for a biomarker that could measure who was responding and predict who would do best.

 

 

Via Krishan Maggon

The central nervous system (CNS) largely comprises nonregenerating cells, including neurons and myelin-producing oligodendrocytes, which are particularly vulnerable to immune cell–mediated damage. To protect the CNS, mechanisms exist that normally restrict the transit of peripheral immune cells into the brain and spinal cord, conferring an “immune-specialized” status. Thus, there has been a long-standing debate as to how these restrictions are overcome in several inflammatory diseases of the CNS, including multiple sclerosis (MS). In this review, we highlight the role of the meninges, tissues that surround and protect the CNS and enclose the cerebral spinal fluid, in promoting chronic inflammation that leads to neuronal damage. Although the meninges have traditionally been considered structures that provide physical protection for the brain and spinal cord, new data have established these tissues as sites of active immunity. It has been hypothesized that the meninges are important players in normal immunosurveillance of the CNS but also serve as initial sites of anti-myelin immune responses. The resulting robust meningeal inflammation elicits loss of localized blood-brain barrier (BBB) integrity and facilitates a large-scale influx of immune cells into the CNS parenchyma. We propose that targeting the cells and molecules mediating these inflammatory responses within the meninges offers promising therapies for MS that are free from the constraints imposed by the BBB. Importantly, such therapies may avoid the systemic immunosuppression often associated with the existing treatments.

Via Krishan Maggon

ABSTRACT

Objective: This study evaluated the efficacy and safety of ATL1102, an antisense oligonucleotide that selectively targets the RNA for human CD49d, the α subunit of very late antigen 4, in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: In a multicenter, double-blind, placebo-controlled randomized phase II trial, 77 patients with RRMS were treated with 200 mg of ATL1102 subcutaneously injected 3 times in the first week and twice weekly for 7 weeks or placebo and monitored for a further 8 weeks. MRI scans were taken at baseline and weeks 4, 8, 12, and 16. The primary endpoint was the cumulative number of new active lesions (either new gadolinium-enhancing T1 lesions or nonenhancing new or enlarging T2 lesions) at weeks 4, 8, and 12.

Results: A total of 72 patients completed the study and 74 intention-to-treat patients were assessed. ATL1102 significantly reduced the cumulative number of new active lesions by 54.4% compared to placebo (mean 3.0 [SD 6.12] vs 6.2 [9.89], p = 0.01). The cumulative number of new gadolinium-enhancing T1 lesions was reduced by 67.9% compared to placebo (p = 0.002). Treatment-emergent adverse events included mild to moderate injection site erythema and decrease in platelet counts that returned to within the normal range after dosing.

Conclusions: In patients with RRMS, ATL1102 significantly reduced disease activity after 8 weeks of treatment and was generally well-tolerated. This trial provides evidence for the first time that antisense oligonucleotides may be used as a therapeutic approach in neuroimmunologic disorders.

Classification: This study provides Class I evidence that for patients with RRMS, the antisense oligonucleotide ATL1102 reduces the number of new active head MRI lesions.

Via Krishan Maggon