According to a press release from the Kentucky-based Apellis Pharmaceuticals, the Company has initiated a program to investigate the use of APL-9, an investigational drug, in gene therapies that involve the use of adeno-associated virus. Adeno-associated virus (AAV) is an inert virus scientists often use in gene therapies to deliver modified segments of DNA that “override” harmful genetic mutations.
Although AAV is not known to cause any diseases, it can trigger an immune response in some individuals. Apellis researchers hope APL-9 will help control these undesirable immune responses.
About Gene Therapy and Adeno-Associated Virus
Gene therapy is an experimental but exciting and increasingly popular field of medical research. It uses genes to treat or prevent certain diseases — especially those with a known genetic component. Most often, it involves the modification or introduction of genes through surgical or pharmaceutical means.
One of the most popular ways of administering these modified genes is through the use of the adeno-associated virus, or AAV. AAV, like other viruses, is exceptionally small and excels at penetrating the body’s defenses. It, like other viruses, is capable of injecting some of its genetic material into that of a host cell. That’s what makes it so appealing to researchers.
By modifying the genetic code contained in the AAV, researchers can “program” the virus to deliver working versions of commonly malfunctioning genes. The results can be impressive. Certain cancers and neurodegenerative diseases can be treated with gene therapies, which tend to be expensive but can provide significant benefits with a single treatment — as opposed to often physically demanding treatment alternatives.
However, there is some evidence that suggests that the body’s tolerance of AAV is related to unfamiliarity — once gene therapy has been administered through AAV, the immune system may develop antibodies capable of responding to the protein shell that forms the outermost layer of a virus. These antibodies can reduce the efficiency of the modified viruses, and therefore the efficiency of gene therapies. They can also prevent future re-administration of the modified AAV, should it be required.
About APL-9 and AAV Immune Response
Although gene therapies can provide amazing benefits, their price tags are consistently among the heftiest in medicine. The possibility of developing an immune response to AAV is a reality gene therapy scientists are working tirelessly to counter.
APL-9 is thought to work by modulating C3 proteins, which play an important role in the complement immune system — part of the immune system that enhances the natural abilities of antibodies and phagocytes.
APL-9 was found to be safe and tolerable in a phase 1 study of 20 healthy individuals, but years of testing will be required before the investigative drug is read for application to the US Food and Drug Administration.
Despite rapid advances in the field of gene therapy, significant hurdles remain. Would the risk of developing AAV resistance dissuade you from undergoing a possibly expensive gene therapy treatment? Share your thoughts with Patient Worthy!
