War Against Ourselves

A biopharmaceutical (a.k.a. biologic) is a drug that is based off of biological sources (like proteins, cells, sugar etc.). This type medicine is used to treat many illnesses including: arthritis, heart disease, cancer, and hemophilia. Unfortunately, the use of biologics can trigger immune responses and the release of antidrug antibodies (ADAs). For example, the protein biologic inserted for hemophilia can trigger immunogenic responses. Hemophilia is a disease where every injury causes uncontrollable bleeding. This disorder is caused by the lack of the Factor VIII protein (a protein which is responsible for creating blood clots). People with this disease inject themselves with Factor VIII. However, some people’s bodies launch the immune system using ADAs against the protein. The drug is destroyed and it cannot affect the body.

Researchers are looking for new strategies to increase immune tolerance for the drugs. Some strategies include: teaching the immune system to ignore biologics or building biologics that do not raise immunogenic responses in the first place.

Researchers at Selecta Biosciences have developed a way to administer Factor VIII to the body by suppressing the body’s immune response. Nanoparticles containing Factor VIII and rapamycin (a drug that can restrain immune responses) is administered to the lymph nodes. There, the nanoparticles prompt the dendritic cells (messenger cells) to create tolerance for Factor VIII. This procedure successfully decreases the number of Factor VIII antibodies.

Another approach is to eliminate use of the Factor VIII completely. Chugai, a Japanese drug company, developed a way to mimic the actions of the Factor VIII. Factor VIII causes Factor IX and Factor X to bond and create a clot. Researchers created an antibody that becomes the chemical bridge between the two proteins, thereby avoiding usage of Factor VIII completely. This approach reduced bleeding in adults by 87%, and was approved by the FDA in November 2017.

Alnylam Pharmaceuticals developed a way to use RNA interference to create changes in human cells (by suppressing or silencing part of the RNA). They created a drug that removes a protein that stops the production of thrombin. Thrombin is a blood clotting protein. The lack of the thrombin-suppressing protein causes an increase in the production of thrombin and reduces bleeding.

Although we have had many great discoveries int eh field of biopharmaceuticals, we still need to learn more. For example: we know how to treat ADA prone patients with hemophilia, but what about other diseases?