A Phase 2, Multicentre, Double-Blind, Placebo-Controlled, Dose Escalating Trial of the Safety, Pharmacokinetics, and Biological Activity of 3 Consecutive Daily Doses of Serp-1 When Added to Conventional Therapy in Patients With Acute Coronary Syndromes (Non ST-Elevation Myocardial Infarction and/or Unstable Angina)

Males and females aged 18-80 years who present with ACS (unstable angina and non ST-elevation MI) defined as one or more episodes of angina lasting at least 5 minutes in the last 24 hours before admission and greater than 0.05 mV of presumed new ST-segment depression in at least 2 contiguous ECG leads OR, angina and per confirmatory angiogram, has been scheduled for percutaneous coronary angioplasty. The primary objective of this study is to evaluate the safety of Serp-1 injection when administered in 3 daily doses to patients undergoing conventional therapy for Acute Coronary Syndrome (ACS) requiring early intervention.

Start Date01 Oct 2005

Sponsor / Collaborator

Viron Therapeutics, Inc.

100 Clinical Results associated with VT-111

100 Translational Medicine associated with VT-111

100 Patents (Medical) associated with VT-111

Literatures (Medical) associated with VT-111

01 Nov 2021·Current NeuropharmacologyQ2 · MEDICINE

Serine Proteases and Chemokines in Neurotrauma: New Targets for Immune Modulating Therapeutics in Spinal Cord Injury

Q2 · MEDICINE

Review

Author: Varkoly, Kyle S. ; Burgin, Michelle ; Guo, Qiuyun ; Zhang, Liqiang ; Beladi, Roxana N. ; Dobrowski, Wojciech ; Yaron, Jordan R. ; Schutz, Lauren ; Hogue, Ian ; Tierney, Wesley ; Lucas, Alexandra R.

:Progressive neurological damage after brain or spinal cord trauma causes loss of motor function and treatment is very limited. Clotting and hemorrhage occur early after spinal cord (SCI) and traumatic brain injury (TBI), inducing aggressive immune cell activation and progressive neuronal damage. Thrombotic and thrombolytic proteases have direct effects on neurons and glia, both healing and also damaging bidirectional immune cell interactions. Serine proteases in the thrombolytic cascade, tissue- and urokinase-type plasminogen activators (tPA and uPA), as well as the clotting factor thrombin, have varied effects, increasing neuron and glial cell growth and migration (tPA), or conversely causing apoptosis (thrombin) and activating inflammatory cell responses. tPA and uPA activate plasmin and matrix metalloproteinases (MMPs) that break down connective tissue allowing immune cell invasion, promoting neurite outgrowth. Serine proteases also activate chemokines. Chemokines are small proteins that direct immune cell invasion but also mediate neuron and glial cell communication. We are investigating a new class of therapeutics, virus-derived immune modulators; One that targets coagulation pathway serine proteases and a second that inhibits chemokines. We have demonstrated that local infusion of these biologics after SCI reduces inflammation providing early improved motor function. Serp-1 is a Myxomavirus-derived serine protease inhibitor, a serpin, that inhibits both thrombotic and thrombolytic proteases. M-T7 is a virus-derived chemokine modulator.:Here we review the roles of thrombotic and thrombolytic serine proteases and chemoattractant proteins, chemokines, as potential therapeutic targets for SCI. We discuss virus-derived immune modulators as treatments to reduce progressive inflammation and ongoing nerve damage after SCI.

01 Aug 2021·Clinical ImmunologyQ3 · MEDICINE

Myxomavirus serpin alters macrophage function and prevents diffuse alveolar hemorrhage in pristane-induced lupus

Q3 · MEDICINE

Article

Author: Reeves, Westley H ; Lu, Li ; Zhuang, Haoyang ; Han, Shuhong

C57BL/6 mice with pristane-induced lupus develop macrophage-dependent diffuse alveolar hemorrhage (DAH), which is blocked by treatment with liver X receptor (LXR) agonists and is exacerbated by low IL-10 levels. Serp-1, a myxomavirus-encoded serpin that impairs macrophage activation and plasminogen activation, blocks DAH caused by MHV68 infection. We investigated whether Serp-1 also could block DAH in pristane-induced lupus. Pristane-induced DAH was prevented by treatment with recombinant Serp-1 and macrophages from Serp1-treated mice exhibited an anti-inflammatory M2-like phenotype. Therapy activated LXR, promoting M2 polarization and expression of Kruppel-like factor-4 (KLH4), which upregulates IL-10. In contrast, deficiency of tissue plasminogen activator or plasminogen activator inhibitor had little effect on DAH. We conclude that Serp-1 blocks pristane-induced lung hemorrhage by enhancing LXR-regulated M2 macrophage polarization and KLH4-regulated IL-10 production. In view of the similarities between DAH in pristane-treated mice and SLE patients, Serp-1 may represent a potential new therapy for this severe complication of SLE.

01 Jan 2021·Methods in Molecular Biology

Neurologic and Histologic Tests Used to Measure Neuroprotective Effectiveness of Virus-Derived Immune-Modulating Proteins

Article

Author: Delaney, Kathleen H ; Kwiecien, Jacek M ; Lucas, Alexandra R ; Yaron, Jordan R

Severe inflammatory disease initiated by neurotrauma and stroke is of primary concern in these intractable pathologies as noted in recent studies and understanding of the pathogenesis of spinal cord injury (SCI) in the rat model. Successful anti-inflammatory treatments should result in neuroprotection and limit the loss of neurological function to injury caused by the initial damage. Continuous subdural infusion offers direct access to the cavity of injury (COI) that forms after balloon crush SCI deep in the spinal cord. Some anti-inflammatory compounds are not likely capable of crossing the blood-spinal cord barrier. Subdural infusion of myxoma virus-derived Serp-1, an anti-thrombotic/anti-thrombolytic, and also of M-T7, a chemokine inhibitor, improved the locomotor scores and pain sensation scores as well as reduced the numbers of macrophages in the COI by 50 and 80%, respectively, while intraperitoneal infusion of either protein had little effect. Injection of a chitosan hydrogel loaded with Serp-1 into the dorsal spinal column crush also resulted in improved neurological deficits and in reduction of the size of the crush lesion 4 weeks after injury. While neurological scores in a simplified hind-end (HE) locomotor test together with a toe-pinch withdrawal test demonstrated improvement in all balloon crush injury and dorsal spinal crush injury rats, a severe inflammation is induced by the injury indicating additional damage to the spinal cord. Thus neurological function testing can be contradictory, rather than corresponding, to the pathogenesis of SCI. The count of macrophages in the COI offers a precise, reliable method of measuring the effectiveness of a neuroprotective treatment of SCI in preclinical studies.

100 Deals associated with VT-111

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Coronary Syndrome	Phase 2	CA	Viron Therapeutics, Inc.	01 Oct 2005
Acute Coronary Syndrome	Phase 2	US	Viron Therapeutics, Inc.	01 Oct 2005
Angina, Unstable	Phase 2	US	Viron Therapeutics, Inc.	01 Oct 2005
Angina, Unstable	Phase 2	CA	Viron Therapeutics, Inc.	01 Oct 2005
Coronary Artery Disease	Phase 2	CA	Viron Therapeutics, Inc.	01 Oct 2005
Coronary Artery Disease	Phase 2	US	Viron Therapeutics, Inc.	01 Oct 2005
Coronary Restenosis	Phase 2	US	Viron Therapeutics, Inc.	01 Oct 2005
Coronary Restenosis	Phase 2	CA	Viron Therapeutics, Inc.	01 Oct 2005
Non-St Elevated Myocardial Infarction	Phase 2	CA	Viron Therapeutics, Inc.	01 Oct 2005
Non-St Elevated Myocardial Infarction	Phase 2	US	Viron Therapeutics, Inc.	01 Oct 2005

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