desmoteplase (recombinant Desmodus Salivary Plasminogen Activator alpha 1) / Lundbeck - LARVOL DELTA

Novel thrombolytic agents for acute ischemic stroke: A comprehensive review of current evidence. (PubMed, J Neurol Sci) - "Over the last decades, alteplase (recombinant tissue type plasminogen activator, rt-PA) has been established as the main thrombolytic agent worldwide...This review summarizes current clinical evidence and emerging research on novel thrombolytic agents in acute ischemic stroke, including tenecteplase, reteplase, desmoteplase, urokinase, staphylokinase, JX10, LT3100, Ancrod, and TS23. Among these agents, tenecteplase has been most extensively studied and is already recommended for selected indications by the European Stroke Organization (ESO) and the American Heart Association and American Stroke Association (AHA/ASA). Other agents are still undergoing early clinical investigation and show different levels of potential in terms of effectiveness, safety, and ease of administration."

Journal • Cardiovascular • Ischemic stroke

FIBRIN SELECTIVE ALTEPLASE WITH IMPROVED THROMBOLYSIS AND INHIBITION RESISTANCE ENGINEERED BY RATIONAL DESIGN (WSC 2023) - "The designs comprised alteplases with mutations suppressing the side effects, reconstructed ancestral alteplases, and database-mined sequences related to alteplase or a vampire bat thrombolytic desmoteplase. Collectively, our results provide a new modified drug candidate with a promising therapeutic potential of becoming a safer and more effective thrombolytic."

Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke

Identification, characterization, and engineering of glycosylation in thrombolyticsa. (PubMed, Biotechnol Adv) - "Practical examples from previous studies focus on modification of glycosylations in thrombolytics, e.g., alteplase, tenecteplase, reteplase, urokinase, saruplase, and desmoteplase. Directed evolution pipelines would benefit from more efficient cell-free expression and high-throughput screening assays, while rational design must employ structure prediction by machine learning and in silico characterization by supercomputing. Perspectives on challenges and opportunities for improvement of thrombolytic enzymes by engineering and evolution of protein glycosylation are provided."

Journal • Review • Cardiovascular • Ischemic stroke • Myocardial Infarction • Pulmonary Embolism • Respiratory Diseases

"Your table is another common misinformation tactic: 1⃣Grouping vastly different trials comparing 🍎 to 🍊 -5 of the trials listed are not on tPA! -Streptokinase trials included concomitant ASA + heparin, known to ⬆️ bleeding -Desmoteplase trials included pts up to 9hrs." (@4mmk36)

Clinical

The Efficacy and Safety of Ischemic Stroke Therapies: An Umbrella Review. (PubMed, Front Pharmacol) - "The results showed that thrombolytic therapy (tPA; alteplase, tenecteplase, and desmoteplase), mechanical thrombectomy (MTE), edaravone with tPA, stem cell-based therapies, stent retrievers, acupuncture with Western medicines, autologous bone marrow stromal cells, antiplatelet agents (aspirin, clopidogrel, and tirofiban), statins, and Western medicines with blood-activating and stasis-dispelling herbs (NaoShuanTong capsule, Ginkgo biloba, Tongqiao Huoxue Decoction, Xuesaitong injection) can improve the neurological deficits and activities of daily living, and the adverse effects were mild for the treatment of ischemic stroke. Moreover, ligustrazine, safflower yellow, statins, albumin, colchicine, MLC601, salvianolic acids, and DL-3-n-butylphthalide showed serious adverse events, intracranial hemorrhage, or mortality in ischemic stroke patients. Our study demonstrated that tPA, edaravone and tPA, tPA and MTE, acupuncture and Western medicines, and blood-activating and..."

Review • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Immunology • Ischemic stroke

Clinical Pharmacokinetics and Pharmacodynamics of Desmoteplase. (PubMed, Eur J Drug Metab Pharmacokinet) - "Desmoteplase was tested in myocardial infarction and pulmonary embolism and showed promising results versus alteplase. However, DIAS-4 was stopped as it might have not reached its primary endpoint. Due to its promising properties, desmoteplase may be added into treatment of ischemic stroke with extension of the time window and special emphasis on patients presenting outside the 4.5-h thrombolysis window, with wake-up strokes and strokes of unknown onset."

Clinical • Journal • PK/PD data • Review • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Immunology • Ischemic stroke • Myocardial Infarction • Pulmonary Embolism • Respiratory Diseases

Corneal and scleral permeability of Desmoteplase in different species. (PubMed, Vet Ophthalmol) - "Desmoteplase has the ability to permeate both cornea and sclera ex vivo in all species tested. Implications of the ex vivo permeability of DSPA suggest that in vivo permeability may be possible, and if so, it could lead to a novel topical application for lysing fibrin."

Journal • Complement-mediated Rare Disorders • Ocular Inflammation • Ophthalmology • Uveitis

Fibrinolytic Capacity of Desmoteplase Compared to Tissue Plasminogen Activator in Rabbit Eyes. (PubMed, J Ocul Pharmacol Ther) - "DSPA is a promising drug with fewer side effects and similar fibrinolytic efficacy compared with t-PA 24 h after intracameral application in rabbit eyes at the tested concentration. Drug efficacy might be improved by increasing intracameral DSPA doses."

Journal • Complement-mediated Rare Disorders • Ophthalmology • Uveitis

Desmoteplase After Ischemic Stroke in Patients With Occlusion or High-Grade Stenosis in Major Cerebral Arteries. (PubMed) - Stroke - No abstract available.

Journal • Biosimilar • Reperfusion Injury

Design and production of new chimeric reteplase with enhanced fibrin affinity: a theoretical and experimental study. (PubMed, J Biomol Struct Dyn) - "The newer generation of PAs like tenecteplase, reteplase and desmoteplase were designed with the aim of achieving desirable properties such as improving specificity and affinity to fibrin and increasing half-life...Experimental assessment showed both mutants have appropriate enzymatic activity also 1.9-fold fibrin binding ability compared to wild type. Therefore, this study offers new thrombolytic drugs with desirable properties specially enhanced fibrin affinity so they can represent a promising future in cost-effective production of favorable thrombolytic drugs."

Journal

Thrombolytic Therapy for Acute Ischemic Stroke: Past and Future. (PubMed, Curr Pharm Des) - "Thrombolytic therapy is sometimes accompanied by harmful hemorrhagic insults; accordingly, a window of time wherein therapy can safely be performed has been established for this approach. Several basic and clinical studies are ongoing to develop next-generation thrombolytic drugs to expand the time window."

Journal

Thrombolytic therapy of ischemic stroke (PubMed, Zh Nevrol Psikhiatr Im S S Korsakova) - "Another group of thrombolytic agents includes derivatives of flora and fauna - external plasminogen activators, of which streptokinase, staphylokinase, and desmoteplase are most common drugs. These medications are not a structural part of the human organism, and overcoming of immunogenicity while preserving fibrinolytic activity and fibrin specificity is one of the main tasks in applying them in clinical practice."

Journal

The Benefit of IV Thrombolysis in Acute Ischemic Stroke: Meta-Analysis of All Trials at the (Near) Close of the Standalone IV Lytic RCT Era (ISC 2019) - "...Agents tested were tissue plasminogen activator (tPA), urokinase, streptokinase, and desmoteplase... The (near) final accumulated evidence confirms that, as a class, IV thrombolytics are beneficial for acute ischemic stroke patients with disabling deficits, and are the appropriate foundation for further advances in acute cerebral ischemia therapeutics."

Retrospective data