Turning animals into walking drug producers: F.D.A. approves antithrombin from genetically engineered goats

The intravenous therapy, ATryn, is purified from the milk of the genetically engineered goats.

One genetically engineered goat can produce as much antithrombin in a year as can be derived from 90,000 blood donations. GTC Biotherapeutics antithrombin is the first drug from genetically engineered animals.


ATryn. Photo compliments of LEO Pharma. Image source: GTC Biotherapeutics.


Antithrombin monomer drawn from PDB. Image source: Wikipedia, public domain.

Antithrombin (AT) is a small protein molecule that inactivates several enzymes of the coagulation system. It is a glycoprotein produced by the liver and consists of 432 amino acids.


The coagulation cascade. Image source: Wikipedia, GNU Free Documentation License.

Antithrombin is a serine protease inhibitor (serpin) that degrades the serine proteases: thrombin, FIXa, FXa, FXIa, and FXIIa. It is constantly active, but its adhesion to these factors is increased by the presence of heparan sulfate (a glycosaminoglycan) or the administration of heparins (different heparinoids increase affinity to FXa, thrombin, or both).

Quantitative or qualitative deficiency of antithrombin leads to thrombophilia. Hereditary AT deficiency occurs in a small population (approximately 1 in 5,000 people in the United States). The first family suffering from inherited antithrombin deficiency was described in 1965. These patients are at high risk of blood clots during medical interventions, such as surgery, and before, during and after childbirth.

References:
F.D.A. Approves Drug From Gene-Altered Goats. NYT.
GTC Drug Is First From Genetically Engineered Animals. Bloomberg.
Antithrombin, from Wikipedia, the free encyclopedia.
Coagulation, from Wikipedia, the free encyclopedia.
FDA Approves Orphan Drug ATryn to Treat Rare Clotting Disorder. FDA.