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As FTM posted, Dr. Philip Thorpe is co-author of an oral abstract pres. at “American Heart Assoc. Scientific Sessions”, LosAngeles on Nov. 7, 2012. The subject is potential therapies to combat thrombosis/clotting issues common with Antiphospholipid Syndrome (APS). Seems that APS thrombosis is caused by the disruption of the production of nitric oxide (NO) by something or other I can’t follow – involves B2GPI… Anyway, Dr. Thorpe is a co-author.

I found a 12-2010 article on the subject *SEE BELOW* (in which Dr. Thorpe is “involved”), that talks about “3 novel therapeutic interventions that are based on the new understanding of APS”. Whether any of those are Dr. Thorpe’s/Peregrine’s Px-Targeting compounds or not, I don’t know.

However, I did find this from a 12-1-10 J.Clin Invest. article ( http://tinyurl.com/24ddq8h ) about potential ”novel therapies for APS (antiphospholipid syndrome)”, a disease that can cause life-threatening clotting disorders. One of the mabs tested was the “anti-B2GPI mouse monoclonal antibody 2aG4, which is a mouse IgG2a version of murine mab ‘3G4’, from which (chimeric) Bavituximab was derived.” – again, see below.

Nov3-7 2012: “American Heart Assoc. Scientific Sessions”, LosAngeles

http://my.americanheart.org/professional/Sessions/ScientificSessions/Scientific-Sessions_UCM_316900_SubHomePage.jsp
Program: http://www.nxtbook.com/tristar/aha/final_program2012/index.php
Abstract Search: http://www.abstractsonline.com/plan/AdvancedSearch.aspx

Abstract Oral Session (Nov 7, 2012, 9:00-10:25am)
AOS.703.02: “Novel Signaling Pathways in the Regulation of Endothelial Function”
Core7: Vascular Disease: Biology & Clinical Science
6 Oral Presentations, including:
• Nov 7, 2012, 10:00-10:15am #13186: “Development of Novel, Mechanism-Based Therapies to Prevent the Cardiovascular Complications of the Antiphospholipid Syndrome”
Authors: Victoria Ulrich, Philip Shaul, Philip Thorpe, Chieko Mineo, UTSW/Dallas
Specialty: +703. Endothelium, Vascular Tone & Nitric Oxide
Keywords: Endothelial function; Nitric oxide; Cardiovascular therapeutics; Thrombosis; Angiogenesis
Disclosures – all Nones, except:
P. Thorpe: Other Research Support; Significant; Peregrine Pharm.; Ownership Interest; Significant; Peregrine Pharm.; Consultant/Advisory Board; Significant; Peregrine Pharm.
ABSTRACT:
Patients with antiphospholipid syndrome (APS) have circulating antiphospholipid antibodies (aPL) and increased risk of thrombosis as well as non-thrombotic vascular disease. Current APS treatment is limited to anticoagulation, which targets only a portion of APS-related disease and has modest efficacy and serious potential complications. We previously showed that aPL antagonism of endothelial NO synthase (eNOS) underlies APS-associated thrombosis. Seeking to develop therapies directed at the initiating processes for both APS-related thrombosis and non-thrombotic vascular disease, we studied the basis for eNOS antagonism by aPL and also determined how aPL impact endothelial repair. In scratch assays with bovine aortic endothelial cells (BAEC), we found that in contrast to IgG from normal healthy subjects (NHIgG) which had no effect, polyclonal aPL from APS patients inhibited migration stimulated by VEGF. The migratory response was restored by the NO donor S-nitroso-N-acetylpenicillamine, a monoclonal antibody (mAb) to the cell surface protein B2GPI had effects identical to aPL, and aPL antagonism of migration was prevented by siRNA knockdown of apolipoprotein E receptor 2 (apoER2). Thus, the B2GPI/apoER2-mediated eNOS antagonism that we previously discovered underlies aPL-induced thrombosis also antagonizes endothelial cell migration. Mimicking the cell culture findings, in C57BL/6 male mice carotid artery reendothelialization was attenuated by aPL treatment, and this was fully prevented by the NO donor molsidomine. We then screened a series of mAb to ß2GPI in assays of eNOS activation in BAEC. Whereas many mirrored aPL and antagonized eNOS, one anti-ß2GPI mAb designated 1N11 had no effect when tested alone and it fully prevented aPL action. 1N11 also prevented aPL inhibition of endothelial cell migration, and it rescued normal carotid artery reendothelialization in aPL-treated mice. Thus, by bypassing or disrupting how aPL antagonize eNOS, an NO donor or a select mAb to B2GPI can afford protection from the endothelial actions of aPL that underlie the vascular manifestations of APS. Such mechanism-based therapies offer the promise of greater efficacy and fewer complications in patients with this often life-threatening disorder.

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3-Dec-2010: “UT Southwestern Researchers Uncover Culprits in Life-Threatening Clotting Disorder”
http://www.eurekalert.org/pub_releases/2010-12/usmc-usr120310.php
DALLAS – Dec. 3, 2010 – Thanks to findings by UT Southwestern Medical Center researchers, individuals with a potentially life-threatening condition predisposing them to blood clots, or thrombosis, might someday receive therapy to prevent the condition. The findings, available online and in a future issue of The Journal of Clinical Investigation, offer new clues into the mechanisms underlying antiphospholipid syndrome (APS). "Patients with APS have circulating antibodies that cause exaggerated thrombosis. The longstanding mystery has been how these antibodies initiate the clotting," said Dr. Philip Shaul, professor of pediatrics and senior co-author of the study.


IMAGE: An investigation led by Drs. Philip Shaul & Chieko Mineo offers new clues into the mechanisms underlying antiphospholipid syndrome, a potentially life-threatening condition predisposing people to blood clots.

For the study, the researchers first examined the direct actions of APS antibodies on cultured endothelial cells, which line the inside of blood vessels. They discovered that the thrombosis-inducing antibodies recognize a protein called Beta2-Glycoprotein I on the endothelial cell surface that then interacts with a second protein, apolipoprotein E receptor 2 (apoER2). ApoER2 ultimately inactivates the enzyme that produces the antithrombotic molecule nitric oxide. The decrease in nitric oxide causes both white blood cells and platelets to bind to the endothelium, initiating the thrombosis. Dr. Shaul said the findings are quite promising because they identify the series of molecular events responsible for the exaggerated thrombosis. The study also found that in contrast to normal mice, mice genetically engineered to lack apoER2 are completely protected from developing thrombosis when they are given APS antibodies collected from individuals with the syndrome. "Patients with thrombosis often require lifelong anti-coagulation therapy," he said. "The problem with this approach is that the anti-coagulation can be ineffective, and there are multiple potential serious complications related to bleeding. It makes much more sense to develop new therapies that target the underlying disease mechanism." Dr. Chieko Mineo, assistant professor of pediatrics and senior co-author of the study, said the findings are particularly important for pregnant women with APS because they are at high risk of miscarriage and preterm birth. "Even if a woman with APS does carry to term, the infant is often smaller than normal and can suffer from multiple complications," Dr. Mineo said. "Our ongoing studies indicate that the mechanisms we have identified that provoke thrombosis are also operative in APS during pregnancy to adversely affect the health of both the mother and the fetus."

The next step, Dr. Shaul said, is to test in the mouse models 3 novel therapeutic interventions that are based on the new understanding of APS. "If they prevent thrombosis or pregnancy complications in the mouse models, clinical trials would of course follow," Dr. Shaul said.
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Other UT Southwestern researchers involved in the study include lead author Dr. Sangeetha Ramesh, former graduate research assistant in pediatrics; Dr. Cristina Tarango, former postdoctoral fellow in pediatric hematology/oncology; Ivan Yuhanna, senior research associate in pediatrics; Dr. Joachim Herz, professor of molecular genetics and neuroscience; Dr. Philip Thorpe, professor of pharmacology; and Dr. Gail Thomas, former associate professor of internal medicine. Researchers from the University of Rochester School of Medicine and Dentistry, Weill Cornell Medical College and University Medical Center Utrecht in the Netherlands also participated.
The study was supported by the National Institutes of Health, the Alliance for Lupus Research, The Lowe Foundation, the Crystal Charity Ball Center for Pediatric Critical Care Research, and the Robert L. Moore Endowment from Children's Medical Center Foundation.

Another pertinent article:
3-10-11: ” Mechanism Found That Causes Blood Clots In Some Patient”
http://www.betterhealthresearch.com/health-articles/experts-mechanism-found-that-causes-blood-clots-in-some-patients-800277948
“…The scientists said they are hopeful that this discovery will lead to new therapies to help prevent blood clotting, as well as pregnancy complications among APS patients.”

Also this posted on iHub back on 12-3-10:
Dr. Phil Thorpe is a co-author of a 12-1-10 J.Clin Invest. article about potential ”novel therapies for APS (antiphospholipid syndrome)”, a disease that can cause life-threatening clotting disorders. One of the mabs tested was the “anti-B2GPI mouse monoclonal antibody 2aG4”, which is a mouse IgG2a version of murine mab ‘3G4’, from which (chimeric) Bavituximab was derived. See the link below for the entire article.
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=57360406