Although scientists have yet to determine what causes expression ofanti-phospholipid antibodies and why they cause blood clots in somepeople, researchers at La Jolla Pharmaceutical Co. think they'vefound a way to shut down their production.
The discovery, according to Andrew Wiseman, director of businessdevelopment for the San Diego-based company, could lead totreatments for recurrent miscarriages and autoimmune strokes, whichare caused by blood clots. Antibody-mediated strokes mostly strikeyounger adults.
About 10 percent of strokes and recurrent miscarriages that occur inthe U.S. have been linked to presence of anti-phospholipid antibodiesin the blood, said Richard Furie, who is director of systemic lupusand antiviral progression at North Shore University Hospital inManhasset, N.Y. Furie's laboratory has supplied blood containing theantibodies to La Jolla Pharmaceutical for its research.
Current treatments for the strokes and miscarriages, Furie said,involve anticoagulants, which present problems for pregnant womenand which, in general, have significant side effects. Finding a way toselectively knock out the cells that express the antibodies would be asignificant development, he added.
Furie noted that about 40 percent of lupus patients have anti-phosopholipid antibodies in their blood. But he said the antibodiesalso can exist in other people and they don't always causecomplications.
Researchers, he added, so far have been stumped in their efforts topinpoint why B cells express the antibodies and how they causeblood clots.
La Jolla's research involves the development of molecules, which itcalls Toleragens, that are designed to stop B cells from producing thedisease-causing antibodies.
A key element of the Toleragens, which are made with La Jolla'sTolerance Technology, is the use of epitopes that bind to antibodieson the surface of B cells, which are then inactivated.
In the case of anti-phospholipid antibodies, Wiseman said, La Jolla'sresearchers have discovered one or two preferred epitopes that bindto the antibodies. The scientists, he added, are looking for moreepitopes to make sure they have the one that binds the best. Oncethey determine which epitope they want to use they will develop theirdrug candidate.
Although the Toleragen molecules may be able to shut down B cellexpression of anti-phospholipid antibodies, those antibodies alreadyexisting in the blood still have to be treated by other methods.However, Wiseman said, preclinical studies have shown that withinabout a month of turning off their production, the antibodies weregone from the blood system.
Wiseman said the Tolerance Technology applied to the anti-phospholipid antibodies is the same used by La Jolla to develop aToleragen molecule, called LJP 394, to treat lupus. LJP 394 attacksB cells that express double stranded DNA antibodies, which causekidney destruction in lupus patients. The company completed Phase Iof LJP 394 and is gearing up to start Phase II. n
-- Charles Craig
(c) 1997 American Health Consultants. All rights reserved.