Therapeutic Monoclonal Antibodies and Multiple Sclerosis: The Essentials.

Thanks to advances in research, it may soon be easier to diagnose autoimmune diseases earlier, but therapy remains a tricky problem

Auto‐immune diseases are a major health problem in both developed and developing countries: They cause as many deaths as the leading infectious diseases and exact an even greater toll on patients’ quality of life given their chronic nature (Box 1). Reliable data for all auto‐immune diseases are hard to collect, but a 2011 study by the American Autoimmune Related Diseases Association (AARDA) reported that the total annual cost of just seven leading auto‐immune diseases (Crohn's disease, ulcerative colitis, systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), psoriasis, and scleroderma) was somewhere between US$51.8 billion and US$70.6 billion in the USA alone (http://www.diabetesed.net/page/_ files/autoimmune-diseases.pdf). The AARDA report also drew attention to the indirect societal toll with one example being sufferers from RA in the USA, who experienced a decline in average earnings from US$18,409 to US$13,900 per year, and the number of jobs they were able to perform dropped from 11.5 to 2.6 million. It was also found that approximately 50 percent of RA patients were unable to work at all within ten years after disease onset. ### Box 1: Some common auto‐immune diseases #### Graves’ Disease The most common auto‐immune disease in which the body produces antibodies to the receptor for thyroid‐stimulating hormone (TSH). It usually attacks the thyroid, frequently causing it to enlarge to twice its size or more (goiter) and become overactive, with related hyperthyroid symptoms such as increased heartbeat, muscle weakness, disturbed sleep, and irritability. No ideal cure but it can be controlled, with last resort surgical excision of the gland. Other treatments include anti‐thyroid drugs, which reduce the production of thyroid hormone, and radioiodine to shrink the gland and reduce its activity. #### Hashimoto's thyroiditis Another auto‐immune disease of the thyroid gland that involves a variety of cell‐ and antibody‐mediated immune processes. It was the first disease to be recognized as auto‐immune in 1912. In this case, the …

Monoclonal antibodies (mAbs) are described as brand-new tools used in the therapy of cancer, autoimmune and infectious diseases, transplant rejection, and some other new indications.MAbs have been shown to create some adverse events such as hypersensitivity reactions, immunological problems, cardiovascular diseases, respiratory events, proteinuria, nephrotoxicity, dermatologic events, and cytopenia.In this review, our purpose is to overview the indications and the unwanted events matched with these drugs and negotiate the developments in the development of these drugs that are able to increase the efficacy and decrease the safety problems.

McAlpine's Multiple Sclerosis

Immunoproteasome-selective inhibitors: the future of autoimmune diseases?

Epidemiology and Estimated Population Burden of Selected Autoimmune Diseases in the United States

Autoimmune side effects, namely autoantibody (autoAb) occurrence and thyroid function alteration, have been described during interferon-beta (IFN-beta) treatment for multiple sclerosis (MS). AutoAb occurrence and autoimmune thyroid diseases are also frequently detected in MS patients free of any treatment. The aim of this study was to evaluate the relationship between IFN-beta 1b treatment, autoAb occurrence, and autoimmune diseases in MS. Thyroid and liver function and serum autoAb (antithyroid, antinuclear, anti-liver, anti-kidney microsomes, anti-smooth muscle and parietal cell antigens) occurrence were evaluated in 156 relapsing-remitting MS (RRMS) patients before and every 3 months after starting IFN-beta 1b treatment (8 MIU subcutaneously [s.c.] on alternate days). The probability of having liver or thyroid function alteration or autoAb occurrence was analyzed longitudinally with the generalized estimating equations (GEE) approach. At baseline, 16.1% of patients had autoAb. During treatment, autoAb occurred de novo in 7.2% of patients. GEE analysis showed that the probability of having autoAb at any time during IFN-beta 1b treatment did not change significantly compared with baseline. AutoAb occurring de novo rarely persisted during treatment and significantly less than those already present at baseline. Positivity for autoAb at baseline or during treatment was not correlated with the development of thyroid or liver function alteration during IFN-beta 1b treatment. Our study indicates that IFN-beta treatment is a safe treatment for MS patients, free of risk of autoimmunity and of associated liver or thyroid function alteration.

Multiple sclerosis (MS), a chronic demyelinating disorder, is characterized by recurrent neurological deficits or progressive impairment with a high risk of permanent disability. Since the exact pathophysiology and etiology remains still unclear, no curing therapy is currently available. However, several treatments with beneficial effect on relapse rate such as the first line therapies interferon-beta and glatiramer acetate were approved for relapsing-remitting MS. One new important tool in the therapy of MS is the use of monoclonal antibodies. Natalizumab is the first and so far only monoclonal antibody that is approved for MS treatment by the US Food and Drug Administration and the European Medicines Agency. In addition to natalizumab other monoclonal antibodies previously used in cancer and other autoimmune disorders or even newly developed for MS are now being tested in clinical trials. With their high target specificity and efficacy monoclonal antibodies are a promising treatment approach in MS. This review summarizes the present knowledge on the use, effectiveness and safety of monoclonal antibodies in MS treatment.

Multiple sclerosis: New insights and trends

Precision targeting of immune responses is crucial for the ongoing development of therapies for cancer, autoimmune, and infectious diseases. Aptamers, which are short, single-stranded oligonucleotides, are emerging as powerful immunomodulators in precision medicine due to their unique binding properties to immune receptors and cellular markers, as well as their low immunogenicity. This review evaluates the potential of aptamer-guided nanomedicine in targeting immunological components, including T cells, dendritic cells, macrophages, and soluble mediators, to either activate or suppress immune responses. Recent advances in guiding antigen presentation, checkpoint inhibition, and reprogramming of the tumor microenvironment are discussed. The comparative advantages of aptamers over conventional targeting agents (e.g., monoclonal antibodies and peptides) are further examined in terms of tissue penetration, tuning potential, toxicity profiles, and other relevant parameters. While clinical translations of these advances are still emerging, aptamer-based nanomedicine represents a next-generation platform for precision immunotherapy, affording unique modularity and therapeutic specificity to overcome challenges encountered by established immunomodulatory paradigms. Graphical abstract

Background:Aberrant immune responses to viral pathogens contribute to disease pathogenesis. However, the link between endogenous viruses or viral infection and autoimmune diseases is a longstanding mystery in the fields of...

Tolerogenic dendritic cells (tolDCs) are a promising strategy to treat autoimmune diseases since they have the potential to re-educate and modulate pathological immune responses in an antigen-specific manner and, therefore, have minimal adverse effects on the immune system compared to conventional immunosuppressive treatments. TolDC therapy has demonstrated safety and efficacy in different experimental models of autoimmune disease, such as multiple sclerosis (MS), type 1 diabetes (T1D), and rheumatoid arthritis (RA). Moreover, data from phase I clinical trials have shown that therapy with tolDCs is safe and well tolerated by MS, T1D, and RA patients. Nevertheless, various parameters need to be optimized to increase tolDC efficacy. In this regard, one important parameter to be determined is the most appropriate route of administration. Several delivery routes, such as intravenous, subcutaneous, intraperitoneal, intradermal, intranodal, and intraarticular routes, have been used in experimental models as well as in phase I clinical trials. This review summarizes data obtained from preclinical and clinical studies of tolDC therapy in the treatment of MS, T1D, and RA and their animal models, as well as data from the context of cancer immunotherapy using mature peptide-loaded DC, and data from in vivo cell tracking experiments, to define the most appropriate route of tolDC administration in relation to the most feasible, safest, and effective therapeutic use.

Autoreactive T-Cell Responses in Primary Biliary Cirrhosis Are Proinflammatory Whereas Those of Controls Are Regulatory

The development of new highly effective medications with acceptable safety profile targeted at the treatment of multiple sclerosis (MS) is one of the most important problems of modern neurology. In recent years, MS pathogenesis studies and clinical trials of new treatments enabled regulatory authorities of many countries to approve the use of monoclonal antibody pharmaceuticals. At the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), special consideration was given to natalizumab, alemtuzumab, daclizumab, ocrelizumab, rituximab, opicinumab, and ofatumumab. This publication provides an overview of the main results of the Congress. It was noted that decrease of disability rate in MS patients with a view to completely stopping disease progression is the most important objective of the use of the modern medications modifying MS course (MMMSC). Careful analysis is required to assess the long-term effects of the MMMSC and switching algorithms from the first line of MS therapy to the second one, as well as subsequent switching to the other regimens.

DC specific Smad7 deficiency promotes differentiation of tolerogenic DCs able to attenuate EAE