Replacing plasma-derived C1 Esterase inhibitor

Canadian Blood Services (CBS) distributes a plasma protein product called C1-esterase inhibitor (C1INH) that remarkably accounts for 11.4% of the total annual CBS budget. C1INH is a plasma protein that controls kallikrein, another plasma protein that controls fluid balance. C1INH is manufactured from pooled blood donor plasma. It is used to treat patients with Hereditary Angioedema (HAE). HAE patients suffer from lifealtering episodes of sudden, extreme swelling. Swelling of these patients’ faces and limbs affects their quality of life. Swelling in their throats can cut off their airways and threaten their lives. Demand for C1INH concentrates has risen as physicians have shifted to preventative treatment for HAE. However, C1INH is expensive to manufacture and its effects after injection into patients are short-lived. My project aims to replace C1INH concentrates by extending the half-life of C1INH and finding replacement products, that do not involve C1INH, that are simpler and potentially cheaper to manufacture. Using DNA technology, I will fuse C1INH and albumin, a long-lived blood protein, into a new long-lived fusion protein. Another blood product, alpha-1-Antitrypsin (AAT), can also be engineered to control kallikrein. I will also use DNA technology to alter AAT and make it function like C1INH. This research will benefit Canadians long-term by improving access to C1INH replacement therapy.

SHEFFIELD, William

McMaster University

Graduate Fellowship Program

Ontario

$70,000