Alemtuzumab for multiple sclerosis: the new concept of immunomodulation

Abstract Alemtuzumab (Lemtrada®) is a humanized anti-CD52 IgG1 monoclonal antibody that depletes CD52-expressing cells from the circulation. Robust clinical and radiologic data, derived from clinical trials and long-term observational studies, indicate that alemtuzumab induces a marked immunosuppression related to the depletion of circulating T and B lymphocytes. However, recent advances suggest that the long-term clinical effects of alemtuzumab are probably due to unique qualitative changes in the process of lymphocyte repopulation of the immune system. This leads to a particular rebalancing of the immune system. In this paper we review the immunomodulatory mechanisms underlying the therapeutic effect of alemtuzumab in pre-clinical models and in patients with relapsing remitting multiple sclerosis (RRMS), and stress the importance of a monoclonal antibody-based immunosuppression for treating the severe forms of RRMS. Alemtuzumab has many features of the ideal immunomodulatory drug: rapid biological and clinical actions and and long-lasting benefit. Alemtuzumab can be used as rescue therapy or as first line drug in severe-onset MS. Thus, the availability of alemtuzumab constitutes a significant step forward in the therapy of MS

Ofatumumab and Early Immunological Cells Subset Characterization in Naïve Relapsing Multiple Sclerosis Patients: A Real-World Study

Background: Ofatumumab (OFA) is a fully human anti-CD20 monoclonal antibody administered with a 20 mg subcutaneous monthly dosing regimen. Methods: Inclusion criteria were patients: 1) aged 18-55; 2) with a confirmed diagnosis of relapsing Multiple Sclerosis (RMS), per the revised 2010 McDonald criteria; 2) who started OFA according to Italian Medicines Agency prescription rules and within 12 months from the RMS diagnosis; 3) naïve to any disease-modifying therapy. The primary outcome was to offer an overview of cellular subsets of RMS naïve patients (time 0) and then after 4 weeks (time 1) and 12 weeks (time 2) on therapy with OFA in a real-world setting. Results: Fifteen patients were enrolled. CD3+ T cell frequencies were higher at time 1 ( .4, SD 7.7) and time 2 ( .6, SD 5.8) when compared to time 0 (r.4, SD 9.8), p = .013. B naïve cells were barely detectable in the OFA group at time 1 (%0.4, SD 0.5) and 2 (%1.4, SD 2.9) when compared to time 0 ( .5, SD 3.8), p < .001. Conclusion: The progressive and increasing use of anti-CD20 drugs imposes the need for larger, prospective, real-world, long-term studies to characterize further immunophenotypes of patients with RMS treated with OFA

Physical exercise and synaptic protection in human and pre-clinical models of multiple sclerosis

: In multiple sclerosis, only immunomodulatory and immunosuppressive drugs are recognized as disease-modifying therapies. however, in recent years, several data from pre-clinical and clinical studies suggested a possible role of physical exercise as disease-modifying therapy in multiple sclerosis. current evidence is sparse and often conflicting, and the mechanisms underlying the neuroprotective and antinflammatory role of exercise in multiple sclerosis have not been fully elucidated. Data, mainly derived from pre-clinical studies, suggest that exercise could enhance long-term potentiation and thus neuroplasticity, could reduce neuroinflammation and synaptopathy, and dampen astrogliosis and microgliosis. In humans, most trials focused on direct clinical and MRI outcomes, as investigating synaptic, neuroinflammatory, and pathological changes is not straightforward compared to animal models. the present review analyzed current evidence and limitations in research concerning the potential disease-modifying therapy effects of exercise in multiple sclerosis in animal models and human studies

Is transient ischemic attack a minor stroke?

In the current literature, the utility of transient ischemic attack (TIA) diagnosis is under revision by the scientific community and experts. If initially this term was considered a valid diagnostic category, over the years the definition of TIA has been completely subverted, underlining the scientific lability of this nosological entity [...

Volatile organic compound data of ready-to-cook tuna fish-burgers: Time evolution in function of different and/or combined mild preservation technologies and relevant statistical analysis

Volatile organic compound (VOC) composition from ready-to-cook tuna fish-burgers, prepared with and without a protective microbial strain (Lactobacillus paracasei) and/or stored with modified atmosphere packaging (MAP, 5% O2 and 95% CO2), were extracted by headspace solid-phase microextraction and analyzed by gas chromatography-mass spectrometry (HS-SPME-GC-MS) during the burger shelf-life. The collected data showed volatile composition profiles in function of the mild preservation technologies employed and the storage time. Furthermore, statistical data treatment (principal component analysis and Pearson's coefficients) highlighted differences among samples and positive/negative correlations during the storage time. This paper is related to an article already published in LWT (Investigating the effects of mild preservation technology on perishable foods by volatolomics: The case study of ready-to-cook tuna-burgers” https://doi.org/10.1016/j.lwt.2019.108425)

Clarity on Cannabinoid-Based Products in Medicine

The perception of cannabis in society has changed over the last decades, leading to an increasing permissiveness about its use mainly across Western countries. This has happened in parallel to the growing study of the possible role of cannabinoid-based products in medicine. The cannabis plant contents comprise more than one hundred different cannabinoids, each binding differently to numerous human body targets. This cannabinoids administration, either isolated, combining some of them, or as a full plant extract can produce many different risk–benefit effects in humans depending on the product composition. Moreover, we have seen the appearance of synthetic cannabinoids. As expected, doses and different routes of administration introduce further variability. Cannabinoid-based pharmaceutical products authorised for medicinal use after comprehensive research and with approval by regulatory medicines agencies, such as the European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA), should be distinguished from cannabinoid-based products (whether standardised or not) that aimed for medicinal use but lack submitted efficacy, tolerability, and safety scientific evidence for regulatory approval. Distribution of some of the latter products are still allowed in certain geographical areas. There are also cannabinoid products used mainly recreationally or as food supplements and ruled separately. In a detailed white paper, this review describes the present situation, depicting the societal and medical state of the art, collecting the facts-based risk–benefit features of already available cannabinoid-based products, and also the future possibilities in medicine, which can be vast if proper research is develope

Prioritizing progressive MS rehabilitation research: A call from the International Progressive MS Alliance

Cognition; Fatigue; MobilityCognición; Fatiga; MovilidadCognició; Fatiga; MobilitatBackground: People with multiple sclerosis (MS) experience myriad symptoms that negatively affect their quality of life. Despite significant progress in rehabilitation strategies for people living with relapsing-remitting MS (RRMS), the development of similar strategies for people with progressive MS has received little attention. Objective: To highlight key symptoms of importance to people with progressive MS and stimulate the design and implementation of high-quality studies focused on symptom management and rehabilitation. Methods: A group of international research experts, representatives from industry, and people affected by progressive MS was convened by the International Progressive MS Alliance to devise research priorities for addressing symptoms in progressive MS. Results: Based on information from the MS community, we outline a rationale for highlighting four symptoms of particular interest: fatigue, mobility and upper extremity impairment, pain, and cognitive impairment. Factors such as depression, resilience, comorbidities, and psychosocial support are described, as they affect treatment efficacy. Conclusions: This coordinated call to action—to the research community to prioritize investigation of effective symptom management strategies, and to funders to support them—is an important step in addressing gaps in rehabilitation research for people affected by progressive MS

Exploiting the Multifaceted Effects of Cannabinoids on Mood to Boost Their Therapeutic Use Against Anxiety and Depression

The endocannabinoid system (ECS) has been recently recognized as a prominent promoter of the emotional homeostasis, mediating the effects of different environmental signals including rewarding and stressing stimuli. The ECS modulates the rewarding effects of environmental stimuli, influencing synaptic transmission in the dopaminergic projections to the limbic system, and mediates the neurophysiological and behavioral consequences of stress. Notably, the individual psychosocial context is another key element modulating the activity of the ECS. Finally, inflammation represents an additional factor that could alter the cannabinoid signaling in the CNS inducing a “sickness behavior,” characterized by anxiety, anhedonia, and depressive symptoms. The complex influences of the ECS on both the environmental and internal stimuli processing, make the cannabinoid-based drugs an appealing option to treat different psychiatric conditions. Although ample experimental evidence shows beneficial effects of ECS modulation on mood, scarce clinical indication limits the use of cannabis-based treatments. To better define the possible clinical indications of cannabinoid-based drugs in psychiatry, a number of issues should be better addressed, including genetic variability and psychosocial factors possibly affecting the individual response. In particular, better knowledge of the multifaceted effects of cannabinoids could help to understand how to boost their therapeutic use in anxiety and depression treatment