Safety and efficacy of helminth treatment in relapsing-remitting multiple sclerosis: Results of the HINT 2 clinical trial.

BACKGROUND: The hygiene hypothesis suggests that microbial replacement may be therapeutic in allergic and autoimmune diseases. Nevertheless, the results of helminth treatment, including in multiple sclerosis (MS), have been inconclusive. OBJECTIVE: To assess safety and brain magnetic resonance imaging (MRI) activity in subjects with relapsing-remitting multiple sclerosis (RRMS) during oral administration of ova from the porcine whipworm, Trichuris suis (TSO). METHODS: A total of 16 disease-modifying treatment (DMT) naive RRMS subjects were studied in a baseline versus treatment (BVT) controlled prospective study. MRI scans were performed during 5 months of screening-observation, 10 months of treatment, and 4 months of post-treatment surveillance. RESULTS: No serious symptoms or adverse events occurred during treatment. For the cohort, there was a trend consistent with a 35% diminution in active lesions when observation MRIs were compared to treatment MRIs ( p = 0.08), and at the level of individuals, 12 of 16 subjects improved during TSO treatment. T regulatory lymphocytes were increased during TSO treatment. CONCLUSION: TSO is safe in RRMS subjects. Potentially favorable MRI outcomes and immunoregulatory changes were observed during TSO treatment; however, the magnitude of these effects was modest, and there was considerable variation among the responses of individual subjects.

Immune responses in stroke: how the immune system contributes to damage and healing after stroke and how this knowledge could be translated to better cures?

Stroke is one of the leading causes of death and disability worldwide. The long-standing dogma that stroke is exclusively a vascular disease has been questioned by extensive clinical findings of immune factors that are associated mostly with inflammation after stroke. These have been confirmed in preclinical studies using experimental animal models. It is now accepted that inflammation and immune mediators are critical in acute and long-term neuronal tissue damage and healing following thrombotic and ischaemic stroke. Despite mounting information delineating the role of the immune system in stroke, the mechanisms of how inflammatory cells and their mediators are involved in stroke-induced neuroinflammation are still not fully understood. Currently, there is no available treatment for targeting the acute immune response that develops in the brain during cerebral ischaemia. No new treatment has been introduced to stroke therapy since the discovery of tissue plasminogen activator therapy in 1996. Here, we review current knowledge of the immunity of stroke and identify critical gaps that hinder current therapies. We will discuss advances in the understanding of the complex innate and adaptive immune responses in stroke; mechanisms of immune cell-mediated and factor-mediated vascular and tissue injury; immunity-induced tissue repair; and the importance of modulating immunity in stroke.

Contrasting roles of immune cells in tissue injury and repair in stroke: The dark and bright side of immunity in the brain.

Despite considerable efforts in research and clinical studies, stroke is still one of the leading causes of death and disability worldwide. Originally, stroke was considered a vascular thrombotic disease without significant immune involvement. However, over the last few decades it has become increasingly obvious that the immune responses can significantly contribute to both tissue injury and protection following stroke. Recently, much research has been focused on the immune system's role in stroke pathology and trying to elucidate the mechanism used by immune cells in tissue injury and protection. Since the discovery of tissue plasminogen activator therapy in 1996, there have been no new treatments for stroke. For this reason, research into understanding how the immune system contributes to stroke pathology may lead to better therapies or enhance the efficacy of current treatments. Here, we discuss the contrasting roles of immune cells to stroke pathology while emphasizing myeloid cells and T cells. We propose that focusing future research on balancing the beneficial-versus-detrimental roles of immunity may lead to the discovery of better and novel stroke therapies.