Therapeutic Intervention in Multiple Sclerosis with Alpha B-Crystallin: A Randomized Controlled Phase IIa Trial (original) (raw)
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2011
s and Insights From the 2011 European Meeting in MS: Update on New Treatments, Clinical Aspects of MS, and Biomarkers CME Howard Zwibel, MD; Stephen Krieger, MD; Robert Lisak, MD; Andrew Wilner, MD CME Released: 12/09/2011; Valid for credit through 12/09/2012 Introduction Multiple sclerosis (MS) is a neurodegenerative disease that affects 400,000 people in the United States and more than 2.5 million worldwide.[1] It is generally believed to be an autoimmune disease, and it is the most common cause of nontraumatic neurologic disability in young adults.[2,3] Nearly 2 decades ago, the US Food and Drug Administration (FDA) approval of interferon beta-1b inaugurated the era of injectable disease-modifying therapies. Other injectable interferon-beta preparations and glatiramer acetate followed, and all offered reduced relapse rates with low potential for serious adverse events. In 2004, the introduction of natalizumab, a monoclonal antibody against alpha4-integrin that is administered by ...
The present efficacy of multiple sclerosis therapeutics: Is the new 66% just the old 33%?
Neurology, 2009
A challenge for the clinician treating patients with multiple sclerosis (MS) is to determine the most effective treatment while weighing the benefits and risks. Results of the phase 2 and phase 3 studies on natalizumab were received with great interest, in part due to the "improved" risk reduction for relapse rate, disease progression, and MRI metrics observed in comparison to results in trials of beta-interferon and glatiramer acetate. However, comparison across trials is invalid, in large part due to differences in the study populations. The increased efficacy observed in more recent trials has also been attributed to a fundamental change in subjects with MS enrolled in recent trials compared with the prior decade. In this article, we debate the relative efficacy of natalizumab vs the older injectable therapies. Neurology ® 2009;73:984-990 GLOSSARY ARR ϭ absolute risk reduction; CIS ϭ clinically isolated syndrome; DMT ϭ disease-modulating therapy; EDSS ϭ Expanded Disability Status Scale; FDA ϭ Food and Drug Administration; GA ϭ glatiramer acetate; IFN ϭ interferon; MS ϭ multiple sclerosis; NNT ϭ number needed to treat; PML ϭ progressive multifocal leukoencephalopathy; RRMS ϭ relapsing-remitting MS; RRR ϭ relative risk reduction.
Immunopathophysiologic basis of multiple sclerosis and implications for therapy-a narrative review
Pharmacy & Pharmacology International Journal, 2021
Our current understanding of multiple sclerosis (MS) recognizes several immunopathological mechanisms leading to progressive axonal loss, brain atrophy, and neurological and cognitive disability. Autoreactive T cells eluding central tolerance in the thymus enter lymph nodes. There, antigen presenting cells expressing an antigen closely resembling a self-protein or autoantigen, activate CD4+ cells, which then differentiate into proinflammatory T helper cells (Th1 and Th17). These cells release TNF-alpha, causing myelin disruption and oligodendrocyte apoptosis, and INFγ which recruits CD8+ cells, B cells, and monocytes. These cells leave the lymph nodes and enter the CNS. CD8+ cells attack oligodendrocytes synthesizing myelin and exacerbate neuronal damage. Monocytes (macrophages) phagocytose the myelin sheath and release proinflammatory cytokines that enhance the local inflammatory response. MS progression is characterized by diffuse T and B cell infiltrates, astrogliosis and microgliosis. New evidence suggests that memory B cells may represent a principal component of MS etiology and T and B cell autoimmunity may be a secondary driver of MS. Understanding the immunopathological underpinnings of MS has revolutionized the treatment of this neurological autoimmune disease with an array of disease-modifying drugs (DMDs) with mechanisms of action directed at various key points. Ideally, DMDs should be initiated early in the disease course with the goal to reduce disease activity, preserve brain tissue, and limit deterioration in cognitive and physical function. Currently approved DMDs can be broadly categorized into platform therapies (INFs and glatiramer acetate), S1P receptor modulators, fumarates, monoclonal antibodies, and other therapies. DMDs can also be categorized by overall treatment approach: chronic maintenance/escalation therapy and immune reconstitution therapy (IRT). It remains unclear, however, whether IRT agents reset the adaptive immune system or simply result in cell types with different repopulation dynamics. Other therapeutic approaches in clinical development include Bruton's tyrosine kinase inhibitors, remyelination, neuroprotection, and modulation of microbiome triggers.
Neuron, 2003
Neurological 3-to 4-fold risk for MS. Other genes within the HLA Sciences complex, including tumor necrosis factor (TNF)-␣, com-Beckman Center for Molecular Medicine ponents of the complement cascade, and myelin oligo-Stanford University dendrocyte glycoprotein (MOG), are also involved in MS Stanford, California 94305 pathogenesis. However, genes outside the HLA complex also contribute to MS pathogenesis. In fact, genome-based studies of multiplex MS families (more than Multiple sclerosis (MS) is an autoimmune central nerone family member affected) indicate that 10 to 15 chovous system (CNS) demyelinating disease that causes mosomal loci contribute to MS susceptibility. Multiple relapsing and chronic neurologic impairment. Recent genes acting in concert may elevate the risk for MS. observations have altered certain traditional concepts Myelin-Specific CD4 ؉ T Cells Initiate regarding MS pathogenesis. A greater diversity of cell CNS Inflammation types and molecules involved in MS is now evident.
Inflammation Research, 2018
Background Multiple sclerosis (MS) is a chronic and autoimmune disease of the central nervous system (CNS), mainly characterized by inflammatory demyelination, which manifests as relapses and diffuse damage and brain volume loss, both accounting for neurodegeneration, and therefore, physical disability. MS typically affects young adults and is commonly diagnosed in the early years by acute relapses, which then followed through partial or complete remission period. The clinical course of MS is characterized as four major classifications, including relapsing-remitting (RRMS), primary progressive (PPMS), progressive relapsing (PRMS), and secondary progressive (SPMS). Purpose This review provides comprehensive overview of the current treatments and future innovative approaches in the treatment of MS. Results Currently, there is no definite cure for MS. The treatment of MS has mainly been based on the prescription of immunosuppressive and immune-modulating agents. However, a number of disease-modifying treatments (DMTs) have been designed that reduce the attack rate and delay progression and mainly target inflammation settings in these patients. Although remarkable advancements have occurred in the therapy of MS, the rate of progressive disability and early mortality is still worrisome. Recently, a monoclonal antibody (ocrelizumab) was demonstrated to be beneficial in a clinical trial of primary progressive MS. Furthermore, novel treatment strategies concentrating on the remyelination or neuroprotection are under evaluation. Conclusions In spite of prosperous experiences in MS therapy, the future research, hopefully, will bring substantial improvements in the understanding and approaches of MS therapy.
Recent advances in the management of multiple sclerosis
International Journal of Basic & Clinical Pharmacology
Every 5 minutes, someone somewhere in the world is diagnosed with an inflammatory, demyelinating, neurodegenerative disorder known as multiple sclerosis (MS). MS was historically known as "La sclèrose en plaques" which involves the central nervous system (the brain and the spinal cord). It is always considered to be a disease of adulthood but nowadays pediatric MS is also gaining popularity. It is the most common non-traumatic chronic disabling disease of adults. MS is said to have etiology of multifactorial origin. of the myelin structure thereby producing a dysregulated immune system. MS is an ongoing disease with episodes of relapses and remissions whereas the basic pathophysiology remains increasing over time. Since the pathophysiology of MS is very complex, it makes the pharmacotherapy part bit difficult. MS therapy is disease subtype-specific. The drugs which were previously approved for MS lacks efficacy and sometimes possess serious adverse effects and thereby crea...