The New England Journal of Medicine recently published research done at the University of California on a new treatment for hereditary angioneurotic edema (HANE) also called hereditary angioedema (HAE).
HANE or HAE is a rare genetic disorder that leads to unpredictable, disabling and occasionally fatal episodes of swelling. The swelling can occur in any part(s) of the body. It is caused by uncontrolled activity of the contact system components factor X11a and plasma Kallikrein which leads to excessive release of a bradykinin which in turn causes leaky blood vessels (vascular permeability) with the resultant swelling from the fluid that leaks out of the blood vessels.
The most common form is due to reduced production or reduced functionality of a controller protein called C-1-esterase inhibitor. But there are other forms including ones with normal C-1-inhibitor.
This latter group has been difficult to treat with most current therapies because they work by increasing production of function of C-1-inhibitor replace it directly or inhibit Kallikrein or block the bradykinin receptor. The currently available therapies can be used either to treat/stop acute attacks or prophylactically. In general, they work quite well but not 100%. That is why improved therapies are being researched.
The new drug being researched is donidalorsen which is an antisense oligonucleotide that selectively inhibits plasma prekallikrein production. (Say what?) Donidalorsen inhibits the production of plasma prekallikrein by means of ribonuclease (RNase) enzyme that degrades messenger RNA that would otherwise lead to prekallikrein production. The idea is by moving a step earlier in the domino-like chain of events by reducing prekallikrein this will prevent kallikrein and eventually bradykinin.
The UC researchers have conducted a small trial in 32 patients with a 90% reduction in attacks. Moreover, the medication was not prone to causing side effects. Larger trials are underway.