Research by La Jolla Pharmaceutical Company
(Extracted from the last published report on this research, which sadly was never finished)
Regretably this research failed in the more recent trials, but was the most promising trial yet, for Antiphospholipid Syndrome (APS or APLS) treatment.
Delay in Factor Va inactivation
Activated by thrombin, Factor Va (5a) plays a key role in blood coagulation. Factor Va
acts as a co-factor to accelerate clot formation, giving rise to the nickname "accelerin." Factor Va has a strong procoagulant effect, prolonging the duration of
clot formation. The inactivation of Factor Va is fundamental in controlling the clotting process. Factor Va helps accelerate clotting in the event of an injury, but Factor Va
then needs to be rapidly inactivated by the body to prevent the clot from expanding. In normal individuals Factor Va generation and inactivation is regulated by activated
protein C. It has been proposed that anticardiolipin antibodies impair the normal functioning of protein C.
Work in La Jolla Pharmaceutical Company laboratories has confirmed the observations
of Galli, et al. (*1) that anticardiolipin antibodies from Antiphospholipid Syndrome (APS or APLS) patients can delay the inactivation of Factor Va, leading to a prolongation of the clotting process. ACA can be isolated from patients, added to normal human serum and the levels of Factor Va monitored over time. While
in the absence of ACA the normal serum levels of Factor
Va rapidly return to baseline after clotting is initiated, the presence of ACA causes the Factor Va levels to remain elevated. At 20 minutes ACA from a typical patient cause
the levels of Factor Va to be 50% higher than normal. We believe that these significantly higher levels of the procoagulant Factor Va may lead to an increased
tendency to form blood clots. Removal of the ACA by our Tolerance Technology may correct the delay in Factor Va seen in Antiphospholipid Syndrome (APS or APLS) patients and prevent the inappropriate blood clot formation seen with these patients.
Galli, M., Ruggeri, L., Barbui, T., Differential Effects of Anti-b2-Glycoprotein I and Antiprothrombin Antibodies on the Anticoagulant Activity of Activated
Protein C . Blood, 1998, 91: No 6, 19992004.
Late breaking news
Through its pioneering research in the area of antibody-mediated thrombosis, La Jolla
Pharmaceutical discovered the specific region on ß2 GP1 targeted by disease-causing antibodies. These results were published in the Proceedings of the National Academy
of Science (PNAS) in 1998. It was this discovery that enabled the Company to build LJP 1082, a Toleragen that is designed to shut down the B cells that produce antibodies to ß2 GP1.
In a pre-clinical rat model, LJP 1082 drug treatment reduced the level of antibodies and the number of B cells producing these antibodies by up to 90% These findings
suggest that the drug candidate effectively shut down, or tolerized, the targeted B cells responsible for producing these disease-associated antibodies. LJP hopes to
advance LJP 1082 as a potential therapeutic that specifically targets the underlying cause of antibody-mediated thrombosis and avoids unwanted serious side effects.
What a shame this failed and further research was stopped to concentrate on treatments for other diseases.
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Medical Keywords: systemic antiphospholipid antibody syndrome, Antiphospholipid, Antiphospholipid Antibody Syndrome, Antiphospholipid Syndrome, APS, APLS, Hughes
Syndrome, Sticky Blood, Clotting Disorder, Stroke, TIA, PE, death, Antiphospholipid Antibody Syndrome, Antiphospholipid Syndrome, APS, APLS,
Hughes Syndrome, Sticky Blood, Clotting Disorder, Stroke, TIA, PE, death