Recombinant ADAMTS 13 in thrombotic thrombocytopenic pupura

Scully, Marie; Hibbard, Christopher; Ewenstein, Bruce M.

doi:10.18632/oncoscience.380

Cited by 11 publications

(3 citation statements)

References 5 publications

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“…Furthermore, catheter-related complications can occur in patients undergoing long-term infusion. Given these risks, the possibility of preventing cTTP or treating aTTP with recombinant ADAMTS13 has been an attractive one, since the effective levels of activity needed to prevent platelet coagulation have a broad range, the infused volume can be small, and there is reduced risk of allergic reactions or pathogen transmission [99, 100]. High vWF levels seen in stroke and cardiovascular disease could also potentially be mitigated by recombinant ADAMTS13 more safely than by plasma transfusion.…”

Section: Adamts Proteins In Acquired Disordersmentioning

confidence: 99%

ADAMTS proteins in human disorders

2018

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ADAMTS proteins are a superfamily of 26 secreted molecules comprising two related, but distinct families. ADAMTS proteases are zinc metalloendopeptidases, most of whose substrates are extracellular matrix (ECM) components, whereas ADAMTS-like proteins lack a metalloprotease domain, reside in the ECM and have regulatory roles vis-à-vis ECM assembly and/or ADAMTS activity. Evolutionary conservation and expansion of ADAMTS proteins in mammals is suggestive of crucial embryologic or physiological roles in humans. Indeed, Mendelian disorders or birth defects resulting from naturally occurring ADAMTS2, ADAMTS3, ADAMTS10, ADAMTS13, ADAMTS17, ADAMTS20, ADAMTSL2 and ADAMTSL4 mutations as well as numerous phenotypes identified in genetically engineered mice have revealed ADAMTS participation in major biological pathways. Important roles have been identified in a few acquired conditions. ADAMTS5 is unequivocally implicated in pathogenesis of osteoarthritis via degradation of aggrecan, a major structural proteoglycan in cartilage. ADAMTS7 is strongly associated with coronary artery disease and promotes atherosclerosis. Autoantibodies to ADAMTS13 lead to a platelet coagulopathy, thrombotic thrombocytopenic purpura, which is similar to that resulting from ADAMTS13 mutations. ADAMTS proteins have numerous potential connections to other human disorders that were identified by genome-wide association studies. Here, we review inherited and acquired human disorders in which ADAMTS proteins participate, and discuss progress and prospects in therapeutics.

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Section: Adamts Proteins In Acquired Disordersmentioning

confidence: 99%

ADAMTS proteins in human disorders

2018

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“…The completion of the phase I trial of recombinant ADAMTS 13, which was the first-inhuman trial, using increasing doses, offers a significant advancement in the future treatment of patients with hereditary TTP, delivering a pure form of the deficient enzyme, ADAMTS 13. 15 In summary, the international registry presents the impact of hereditary TTP on end-organ damage, which is evident much earlier than expected within the general population; the most prevalent is arterial disease affecting the brain, heart and kidneys. Based on this important international collaborative study, in conjunction with other large cohorts, we must question how we should treat patients in the form of prophylactic ADAMTS 13 replacement ( Figure 1).…”

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confidence: 99%

Hereditary thrombotic thrombocytopenic purpura

Scully¹

2019

Haematologica

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“…Sepsis is often associated with ADAMTS-13 deficiency due to immune-mediated antibodies, and the severity of this deficiency appears to be associated with outcome (185,186). In addition to replacing ADAMTS-13 with recombinant proteins, the therapeutic armamentarium also consists of TPE, potentially eliminating circulating pathogens or (auto-) antibodies in addition to replacing missing or depleted proteins (187,188).…”

Section: Extracorporeal Blood Purificationmentioning

confidence: 99%

Sepsis—Pathophysiology and Therapeutic Concepts

2021

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Sepsis is a life-threatening condition and a global disease burden. Today, the heterogeneous syndrome is defined as severe organ dysfunction caused by a dysregulated host response to infection, with renewed emphasis on immune pathophysiology. Despite all efforts of experimental and clinical research during the last three decades, the ability to positively influence course and outcome of the syndrome remains limited. Evidence-based therapy still consists of basic causal and supportive measures, while adjuvant interventions such as blood purification or targeted immunotherapy largely remain without proof of effectiveness so far. With this review, we aim to provide an overview of sepsis immune pathophysiology, to update the choice of therapeutic approaches targeting different immunological mechanisms in the course of sepsis and septic shock, and to call for a paradigm shift from the pathogen to the host response as a potentially more promising angle.

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Recombinant ADAMTS 13 in thrombotic thrombocytopenic pupura

Cited by 11 publications

References 5 publications

ADAMTS proteins in human disorders

ADAMTS proteins in human disorders

Hereditary thrombotic thrombocytopenic purpura

Sepsis—Pathophysiology and Therapeutic Concepts

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