Research in HIV Therapy Inspires a Replacement of Heparin
"Research that initially began with studying inhibitors of the HIV virus led the development of a replacement for Heparin, a blood-thinner administered after heart surgery, to reduce post-op complications."
Research from Bruce Sullenger “RNA Center for Biomedicine”
November 23, 2019
HIV is a virus that attacks the healthy cells of the body's immune system and renders the patient unable to properly fight off infection. It is estimated that over a million people in the United States are currently infected with the HIV virus for which there is no cure. Heparin on the other hand is a drug commonly administered to patients after they have undergone heart surgery in order to prevent clotting that could block the arteries of the heart. The study of the biochemistry of an HIV inhibitor led researchers to the development of a blood thinner that may be used in place of Heparin to reduce potential complications. This research displays how a single discovery in biochemistry may influence dramatically different areas of medicine and how collaboration can lead to further innovation.
The research began with investigation into an aptamer that would bind to a protein associated with the HIV virus and render it inactive and blocking the replication of the virus. An aptamer is a molecule, in the case of the particular aptamer for HIV one composed of RNA, it acts as an inhibitor that binds to the target protein and renders it inactive. Aptamers can be generated against most proteins, they are generated by running different shapes that can be lab generated through changing the sequence of the aptamer. This then led to researchers generating an aptamer that may bind to immune system proteins in order to treat autoimmune diseases. Researchers cross reacted and inhibited autoantibodies from patients with severe insulin resistance and generated aptamers. While this was a great advancement in the treatment of this form of diabetes, it is a very rare form. Researchers then turned to surgeons to find a more widely applicable application.
Surgeons pointed researchers in the direction of an anticoagulant or blood thinner that could be used in place of Heparin. While widely used Heparin can also cause major bleeding, as it limits the blood's ability to coagulate and therefore stop bleeding. It then takes too much time to reverse, several hours, which in the case of overdose or major bleeding can be fatal.
A drug was then produced to act as an anticoagulant, as well as its aptamer that could be used to quickly reverse its effects in the case of an emergent complication. Compared to the several hours it took to reverse Heparin, the new drug named PCI by the FDA, could be reversed in as little as 20 minutes. Through trials it was also discovered to reduce thrombotic events by 60% compared to Heparin or Bivalirudin, another anticoagulant. Researchers were able to turn a discovery in biochemistry related to a separate area of study through the collaboration of medical professionals and other researchers into a drug stable enough for human trial and the treatment of 2,000 patients with PCI. However, due to the attachment of a molecular known as PEG, used to stabilize the molecule, several patients had severe reactions to the drug. Their blood contained anti-PEG antibodies that recognized the molecule of PCI as foreign and caused severe reactions. As a result, PCI did not pass this stage of testing.
This discovery, while it proved to not truly be a replacement for Heparin, is a testament to the transferability of information between drastically different areas of medicine and the influence that collaboration can have over innovation. The ultimate goal in the end is not to find a replacement for Heparin but instead to continue investigating the vast uses for a single discovery in biochemistry and to continue using it to further medical advancement.