RESEARCH & DEVELOPMENT

Creatures great and small- novel sources of thrombolytics and anticoagulants

- Tracey Wright -

Leeches are making a comeback in medicine. And they're not the only species of bloodsucking creatures to attract researchers' interest. Vampire bats, mosquitoes, ticks, fleas and bedbugs all contain novel pharmaceuticals with potential as cardiovascular agents.

In addition to their role in plastic surgery and microsurgery, leeches may also have a role in fighting heart disease. Hirudin was the world's first anticoagulant isolated from leeches and has been used widely in thrombotic disorders. This leech-derived protein offers advantages over heparin I.2:

o A lower bleeding tendency following administration of high doses.

o More effectively prevents reocclusion within the coronary artery after thrombolytic therapy, angioplasty and coronary artery bypass surgery.

o Acts directly on thrombin and, unlike heparin, doesn't need the cofactor, antithrombin III.

o Is not bound to or inactivated by antiheparin proteins such as platelet factor 4 or

vitronectin.

Table I. Leech-derived protein

Activity Company Phase of develop· ment

Antistasin FactorXa Merck & Co Preclinical inhibitor

Calin Platelet Biopharm Preclinical adhesion inhibitor

Oecorsin Glycoprotein Genentech lib-lila antagonist

Oestabilase Oepolymerises fibrin

Gelin Elastase Biopharm Preclinical inhibitor

Hementin Fibrino(geno) Biopharm PreclInical lytic

Biopharm Preclinical

More to offer But the humble leech has more to offer.

Researchers have isolated the anti platelet factors, decorsin and cal in. Decorsin is a potent antagonist of platelet membrane glycoprotein lIb-IlIa, while calin binds to collagen to specifically inhibit collagen-induced platelet aggregation. Calin has potential in microsurgery and in preventing collagen-induced reocclusion in coronary bypass surgery and atheroma.

ISSN 0156-2703l9210926-00131$1.0cf' Adlalntematlon8l Ltd

r--------------------------.----Table n. Pr tein deri ed from other bloodsucking creature

Bats

TICks

Bedbugs

Mosquitoes

Protein

Oesmokinase

TAP v (tick anticoagulant protein)

Rhodinase

Apyrase

'II Currently in clinical trials

Antistasin is a polypeptide isolated from species of leeches that don't secrete hirudin. This agent works higher up the coagulation cascade, inhibiting Factor Xa. Interestingly, antistasin has antimetastatic properties in addition to its activity in preventing thrombus formation and reocclusion after tissue plasminogen therapy.

'The leech is a living pharmacy. ' Roy T Sawyer. Founder and Managing Director of

Biopharm

Bloodsucking leeches also secrete highly specific salivary enzymes with potential in thrombolysis, including hementin, leech hyaluronidase and destabilase. Hementin's ability to selectively dissolve platelet-rich clots is unique and makes this agent an attractive adjunct to current thrombolytic therapy [see table I].

From bats to bedbugs Vampire bats and bedbugs secrete plasminogen

activators known as desmokinase and rhodinase, respectively. Both creatures also produce a platelet aggregation inhibitor. From ticks we get the tick anticoagulant peptide (TAP), a slow, tight-binding inhibitor of Factor Xa.

'The same animals that gave us the plague and malaria could be our saviours.'

Dr Sawyer

Mosquitoes produce a platelet aggregation inhibitor known as apyrase. They belong to the large group known as Diptera, which comprises many diverse types of bloodsucking flies. Although few substances have been isolated, researchers have isolated a Factor Xa inhibitor from the blackfly and a potent vasodilatory peptide from the sandfly [see table II]. 1. Hirudins: return of the leech? Lancet 340: 579·580.5 Sep 1992 2. Sawyer RT. Thrombolytics and anticoagulants from leeches. Bio/technology 9: 513-518, Jun 1991 ",,"797'

INPHARMA~26 Sep 1992

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