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Beyond the Magic Bullet: Current Progress of Therapeutic Vaccination in Multiple Sclerosis.

ABSTRACT: Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS) characterized by neuroinflammation, neurodegeneration and impaired repair mechanisms that lead to neurological disability. The crux of MS is the patient's own immune cells attacking self-antigens in the CNS, namely the myelin sheath that protects nerve cells of the brain and spinal cord. Restoring antigen-specific tolerance via therapeutic vaccination is an innovative and exciting approach in MS therapy. Indeed, leveraging the body's attempt to prevent autoimmunity, i.e., tolerization, focuses on the underlying cause of the disease and could be the key to solving neuroinflammation. In this perspective, antigen-specific vaccination targets only the detrimental and aberrant immune response against the specific disease-associated antigen(s) involved while retaining the capacity of the immune system to respond to unrelated antigens. We review the experimental approaches of tolerance-inducing vaccination in relapsing and progressive forms of MS that have reached the clinical development phase, including vaccination with autologous T cells, autologous tolerogenic dendritic cells, T cell receptor peptide vaccination, altered peptide ligand, ATX-MS-1467, cluster of differentiation (CD)-206-targeted liposomal myelin basic protein peptides and DNA vaccination. Failures, successes and future directions are discussed.

SUBMITTER: Willekens B

PROVIDER: S-EPMC5976685 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Beyond the Magic Bullet: Current Progress of Therapeutic Vaccination in Multiple Sclerosis.

Willekens Barbara B Cools Nathalie N

CNS drugs 20180501 5

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS) characterized by neuroinflammation, neurodegeneration and impaired repair mechanisms that lead to neurological disability. The crux of MS is the patient's own immune cells attacking self-antigens in the CNS, namely the myelin sheath that protects nerve cells of the brain and spinal cord. Restoring antigen-specific tolerance via therapeutic vaccination is an innovative and exciting approach in MS ther ...[more]

PMID: 29761344

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Project description:Malaria is a major cause of morbidity and mortality in many African countries and parts of Asia and South America. Novel approaches to combating the disease have emerged in recent years and several drug candidates are now being tested clinically. However, it is long before these novel drugs can hit the market, especially due to a scarcity of safety and efficacy data.To reduce the malaria burden, the Medicines for Malaria Venture (MMV) was established in 1999 to develop novel medicines through industry and academic partners' collaboration. However, no reviews were focused following various preclinical and clinical studies published since the MMV initiation (2000) to till date.We identify promising approaches in the global portfolio of antimalarial medicines, and highlight challenges and patient specific concerns of these novel molecules. We discuss different clinical studies focusing on the evaluation of novel drugs against malaria in different human trials over the past five years.The drugs KAE609 and DDD107498 are still being evaluated in Phase I trials and preclinical developmental studies. Both the safety and efficacy of novel compounds such as KAF156 and DSM265 need to be assessed further, especially for use in pregnant women. Synthetic non-artemisinin ozonides such as OZ277 raised concerns in terms of its insufficient efficacy against high parasitic loads. Aminoquinoline-based scaffolds such as ferroquine are promising but should be combined with good partner drugs for enhanced efficacy. AQ-13 induced electrocardiac events, which led to prolonged QTc intervals. Tafenoquine, the only new anti-relapse scaffold for patients with a glucose-6-phosphate dehydrogenase deficiency, has raised significant concerns due to its hemolytic activity. Other compounds, including methylene blue (potential transmission blocker) and fosmidomycin (DXP reductoisomerase inhibitor), are available but cannot be used in children.At this stage, we are unable to identify a single magic bullet against malaria. Future studies should focus on effective single-dose molecules that can act against all stages of malaria in order to prevent transmission. Newer medicines have also raised concerns in terms of efficacy and safety. Overall, more evidence is needed to effectively reduce the current malaria burden. Treatment strategies that target the blood stage with transmission-blocking properties are needed to prevent future drug resistance.

Dataset Information

Beyond the Magic Bullet: Current Progress of Therapeutic Vaccination in Multiple Sclerosis.

Publications

Beyond the Magic Bullet: Current Progress of Therapeutic Vaccination in Multiple Sclerosis.

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