Second-Generation C5 Inhibitors for Paroxysmal Nocturnal Hemoglobinuria

Fattizzo, Bruno; Kulasekararaj, Austin

doi:10.1007/s40259-019-00401-1

Cited by 17 publications

(18 citation statements)

References 52 publications

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“…Nevertheless, eculizumab still faces challenges, including persistent anemia with some patients requiring transfusions, and incomplete C5 inhibition with breakthrough hemolysis (61). This prompted the investigation of several second-generation C5 inhibitors (new mAb, siRNAs and small molecules) (62). Altogether, this ultimately justifies the rationale behind the use of CD-55 and CD-59 silencing as anticancer therapy, especially with establishment of CD-59 knocked out cancer cell lines which can be used for further in vivo investigations (63) (CD66) Carcinoembryonic Antigen (CEA)…”

Section: Insightsmentioning

confidence: 99%

GPI-AP: Unraveling a New Class of Malignancy Mediators and Potential Immunotherapy Targets

2020

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With millions of cases diagnosed annually and high economic burden to cover expensive costs, cancer is one of the most difficult diseases to treat due to late diagnosis and severe adverse effects from conventional therapy. This creates an urgent need to find new targets for early diagnosis and therapy. Progress in research revealed the key steps of carcinogenesis. They are called cancer hallmarks. Zooming in, cancer hallmarks are characterized by ligands binding to their cognate receptor and so triggering signaling cascade within cell to make response for stimulus. Accordingly, understanding membrane topology is vital. In this review, we shall discuss one type of transmembrane proteins: Glycosylphosphatidylinositol-Anchored Proteins (GPI-APs), with specific emphasis on those involved in tumor cells by evading immune surveillance and future applications for diagnosis and immune targeted therapy.

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Section: Insightsmentioning

confidence: 99%

GPI-AP: Unraveling a New Class of Malignancy Mediators and Potential Immunotherapy Targets

2020

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“…The new approaches aim at increasing the drug half-life or subcutaneous (sc) administration of C5 inhibitors (ie, ravulizumab iv, crovalimab sc), at producing small molecules that may be given orally, and at targeting the complement cascade upstream to C5 (including anti-C1, anti-C3 pegcetacoplan, and the alternative pathway factors B and D inhibitors iptacopan and danicopan). 26 , 27 An innovative approach is the use of small interfering RNA (siRNA) molecules capable of inhibiting C5 synthesis, and very preliminary gene therapy. 28 Preclinical and clinical trials showed that novel C5 inhibitors (ECU biosimilars, ECU with longer half-life such as ravulizumab IV or sc, 29 small molecules, 30 , 31 and siRNA 32 ) are effective in inhibiting complement-mediated hemolysis and imply more manageable administration routes/schedules thus improving patient convenience.…”

Section: Novel Therapiesmentioning

confidence: 99%

Managing Fatigue in Patients with Paroxysmal Nocturnal Hemoglobinuria: A Patient-Focused Perspective

Fattizzo¹,

Cavallaro²,

Olíva³

et al. 2022

JBM

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The most frequently reported symptom in patients with paroxysmal nocturnal hemoglobinuria (PNH), a disease characterized by complement mediated hemolysis and chronic anemia, is “fatigue”. The latter seems the best word to communicate patient’ perception of personal health status and disease impact on daily living, namely quality of life (QoL). Objectivating QoL and grading patient’s fatigue is one of the most difficult medical tasks given the highly heterogeneous communication skills of patients and caregivers and the multitude of meanings that might be attributed to this term. Along with anemia, QoL in PNH is also affected by the emotional burden of a chronic life-long disease with heterogeneous treatment requirement, risk of hemolytic exacerbations (breakthrough hemolysis) and of thrombosis. In the last decade, structured surveys and scores have been adapted from cancer settings to evaluate fatigue and QoL in patients with PNH, and to assess the benefit of complement inhibitors in this setting. Eculizumab was the first drug utilized and was shown to improve QoL scores in the registrative trials. However, the intravenous fortnightly administration, the presence of residual anemia, and the risk of extravascular hemolysis are some of the unmet needs impacting QoL under eculizumab. Several novel drugs have been designed to improve patients’ convenience and alleviate anemia and fatigue. In this review, we focus on available studies that evaluated fatigue and QoL in PNH patients, and the effect of old and new therapeutic strategies.

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“…It also varies from eculizumab in that it is a synthesized macrocyclic peptide that is administered subcutaneously. Zilucoplan as well as other second-generation complement inhibitors fix issues with eculizumab, such as the requirement for intravenous treatment and hereditary resistance seen in paroxysmal nocturnal hemoglobinuria (PNH), the illness for which it was first licensed [70].…”

Section: Recent Therapiesmentioning

confidence: 99%

Overview of Myasthenia Gravis Subgroups and its influence on Pregnancy and their Treatment Advances

Wal¹,

Wal²,

Pandey³

et al. 2022

Pharmacophore

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Antibodies that attack the neuromuscular junction induce myasthenia gravis, an immunological illness. Such antibodies assault and degrade postsynaptic molecules in by binding to the postsynaptic muscular end-plate. As a consequence, signal transduction is disrupted, resulting in muscular weakness and fatigability. Developments in our knowledge of the immunological mechanisms that cause myasthenia gravis have paved the way for the development of new targeted immunity treatments. The majority of myasthenia gravis sufferers have a well-managed condition with just minor to moderate symptoms. The goal must be to create more targeted therapies that reduce or enhance tolerance to the well-known and particular autoimmune reactions that result in autoantibody formation and muscular weakening. Several drugs widely used in obstetrics can aggravate the condition. The impact of maternity on myasthenia varies greatly from one woman to the next, as well as from one pregnancy to the next within the same woman. Acetylcholine esterase inhibitors, corticosteroids, and other immunosuppressants, as well as proper rest, are the most common therapy. Intrauterine antibody exposure can cause in utero or neonatal effects in newborns, which are usually temporary. This review focuses on myasthenia gravis subgroups and treatment breakthroughs, as well as the influence of myasthenia gravis on pregnancy and its management.

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Second-Generation C5 Inhibitors for Paroxysmal Nocturnal Hemoglobinuria

Cited by 17 publications

References 52 publications

GPI-AP: Unraveling a New Class of Malignancy Mediators and Potential Immunotherapy Targets

GPI-AP: Unraveling a New Class of Malignancy Mediators and Potential Immunotherapy Targets

Managing Fatigue in Patients with Paroxysmal Nocturnal Hemoglobinuria: A Patient-Focused Perspective

Overview of Myasthenia Gravis Subgroups and its influence on Pregnancy and their Treatment Advances

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