Multiple Sclerosis research studies for holistic treatments

Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray was approved as add-on therapy for spasticity in patients with Multiple Sclerosis (MS). We showed our forty-weeks post-marketing experience regarding efficacy and safety of THC/CBD spray in an Italian cohort of 102 MS patients. Patients were evaluated using the Expanded Disability Status Scale (EDSS) score, the Numerical Rating Scale (NRS) for spasticity, the Ambulation Index (AI), and Timed 25-Foot Walk (T25-FW) at the beginning of treatment and then every 3 months. After four weeks, if a clinically significant improvement in spasticity (at least 20% of baseline NRS score) was not seen, administration of the drug was stopped. In our cohort patients received an average of 6.5±1.6 sprays each day. The mean reduction to the NRS spasticity score was 2.5±1.2 points (p

The immune system is balanced with cells that respond to microbes by developing into effector cells and cells that regulate the activity of effector cells. In many immune responses a subset of effector T cells termed Th17 are necessary for complete immunity because the cytokine IL-17 that they produce is critical to elimination of the pathogen. However, the activity of Th17 must be balance with development of regulatory T cells termed T(regs). Usually, when the activity of the effector cells is excessive and not balanced by regulatory cells of the immune system, there is the increased risk for development of autoimmune s. Therefore in many autoimmune s the activity of Th17 exceeds that of T(regs). Therapeutics for treatment of autoimmune s such as Multiple Sclerosis (MS) have focused upon immunosuppression, immunomodulation, or even immunoablation of effector cells such as Th17 followed by hematopoietic stem cell transplantation. Very few approaches have attempted to therapeutically increase immune regulatory cells such as T(regs) in the treatment of autoimmune . This review will focus upon the potential `or the use of resveratrol, a natural plant compound that has already been shown to be a potent anti-inflammatory compound, as a complementary therapeutic for MS that increases the activity of T(regs) even though it also increases development of Th17.

Background:
Previous studies have shown that PADMA-28, a multicomponent, traditional Tibetan herbal plant preparation possesses a variety of beneficial effects on several experimental models of inflammatory and immune processes, including autoimmune diabetes and autoimmune encephalomyelitis. In humans, PADMA-28 attenuated the symptoms associated with intermittent claudications in atherosclerotic patients. OBJECTIVE:
To assess the effect of PADMA 28 on the immune system, e.g. cytokine (interleukins) production.
DESIGN:
Cytokine production by human blood monocytes (derived from 12 healthy donors) stimulated in vitro, either by endotoxin (LPS) from Salmonella typhi or by lipoteichoic acid (LTA) from group A Streptococci was modulated by PADMA-28.
Results:
The present study showed that an aqueous extract of PADMA-28 strongly decreased the production of the inflammatory cytokines IL-1beta, IL-6, IL-8 and TNF-alpha, and more moderately, also decreased the anti-inflammatory cytokine IL-10 induced by LPS. However, the LTA – induced IL-10 production was [not significantly] increased by the low dose PADMA-28, while not effected at all by the higher dose of PADMA-28. CONCLUSIONS: The data from these finding suggest a possible clinical efficacy of PADMA-28 either in autoimmune and in inflammatory conditions or in post-inflammatory sequelae, as previously shown in in vivo and human studies, probably by decreasing inflammatory cytokines.

Among the many functions of vitamin D (VD) is its role in the immunomodulation of macrophage. As VD deficiency is a wide-spread diet therapy problem, there is a tendency for the public to overdose with vitamin D supplementation which can result in hypercalcemia and several associated disorders. The present study was designed to investigate the possibility that combining low doses of vitamin D with b-sitosterol (SIT), a common phytosterol in the diet without toxicity, enhances the efficacy of the vitamin. Murine macrophages were stimulated with LPS and supplemented with VD3 (80 nM) and SIT (8 ?M) for 24 hr and examined for cell proliferation, the release of nitric oxide (NO) and cytokines and the activation of NF?B. SIT (8 ?M) was found to reduce cell proliferation by 62% while VD3 was found to be not effective. In combination, SIT and VD3 reduced cell proliferation by 75%. The amount of NO released, as influenced by 8 ?M SIT or 80 nM VD3 treatments, was not significantly different from control. Combining SIT and VD3, resulted in a 220% greater increase in NO release compared to control. The SIT + VD3 treatment brought about a significant increase in all the cytokine release, regardless of whether they were pro- or anti-inflammatory. The effects were either additive or synergistic. We conclude that SIT enhances the action of VD3 on the immune function of macrophages which could be beneficial to vitamin D deficient individuals and to those with autoimmune s such as multiple sclerosis.

The etiology of multiple sclerosis (MS) is believed to involve environmental factors, but their identity and mode of action are unknown. In this study, we demonstrate that Ab specific for the extracellular Ig-like domain of myelin oligodendrocyte glycoprotein (MOG) cross-reacts with a homologous N-terminal domain of the bovine milk protein butyrophilin (BTN). Analysis of paired samples of MS sera and cerebrospinal fluid (CSF) identified a BTN-specific Ab response in the CNS that differed in its epitope specificity from that in the periphery. This effect was statistically significant for the Ab response to BTN(76-100) (p = 0.0026), which cosequestered in the CSF compartment with Ab to the homologous MOG peptide MOG(76-100) in 34% of MS patients (n = 35). These observations suggested that intratheccal synthesis of Ab recognizing BTN peptide epitopes in the CNS was sustained by molecular mimicry with MOG. Formal evidence of molecular mimicry between the two proteins was obtained by analyzing MOG-specific autoantibodies immunopurified from MS sera. The MOG-specific Ab repertoire cross-reacts with multiple BTN peptide epitopes including a MOG/BTN(76-100)-specific component that occurred at a higher frequency in MS patients than in seropositive healthy controls, as well as responses to epitopes within MOG/BTN(1-39) that occur at similar frequencies in both groups. The demonstration of molecular mimicry between MOG and BTN, along with sequestration of BTN-reactive Ab in CSF suggests that exposure to this common dietary Ag may influence the composition and function of the MOG-specific autoimmune repertoire during the course of MS.

Experimental autoimmune encephalomyelitis (EAE) induced by sensitization with myelin oligodendrocyte glycoprotein (MOG) is a T cell-dependent autoimmune that reproduces the inflammatory demyelinating pathology of multiple sclerosis. We report that an encephalitogenic T cell response to MOG can be either induced or alternatively suppressed as a consequence of immunological cross-reactivity, or “molecular mimicry” with the extracellular IgV-like domain of the milk protein butyrophilin (BTN). In the Dark Agouti rat, active immunization with native BTN triggers an inflammatory response in the CNS characterized by the formation of scattered meningeal and perivascular infiltrates of T cells and macrophages. We demonstrate that this pathology is mediated by a MHC class II-restricted T cell response that cross-reacts with the MOG peptide sequence 76-87, I GEG KVA LRIQ N (identities underlined). Conversely, molecular mimicry with BTN can be exploited to suppress activity in MOG-induced EAE. We demonstrate that not only is EAE mediated by the adoptive transfer of MOG74-90 T cell lines markedly ameliorated by i.v. treatment with the homologous BTN peptide, BTN74-90, but that this protective effect is also seen in actively induced following transmucosal (intranasal) administration of the peptide. These results identify a mechanism by which the consumption of milk products may modulate the pathogenic autoimmune response to MOG.