Gene-based Therapy

Several medical conditions such as cancer or Huntington’s chorea arise via faults at the genetic level. Many genetic processes remain unknown, and scientists have, rather than trying to replace/repair a gene outright, gained enough insight to target the specific proteins a gene produces. Targeted therapy, in which the understanding of how genes (or defective genes) work drives drug research, promises a greater level of success than screening several thousands of drug molecules at random to find one that is effective.

The drive for these “rationally designed” drugs has shown particular advancement by focusing on previously known processes of a disease. Dasatinib, for example, was developed to attack a specific protein of a specific cancer, chronic myelogenous leukemia (CML). An adult leukemia spurred by inchoate growth of white blood cells, CML occurs when a defective exchange (called a translocation) between chromosomes 9 and 22 produces an abnormal protein, tyrosine kinase. Detection of this translocation is a highly sensitive test for CML; 95% of CML sufferers have it. Chemotherapy, interferon, and bone marrow transplants are radical and carry risk of complication. Dasatinib binds to the abnormal protein and renders it inert. Such “inhibitor” drugs trigger cancer cell death or render cancer-causing genes biochemically inactive. Protease inhibitors for HIV treatment work along similar lines — not targeting the virus, but rather the enzymes it produces for viral replication.

Gene-based medicine goes beyond treatment; it also can serve as an advanced warning. Several conditions are known to develop over time or run in families — conditions that, if identified early, can be lessened or even avoided. This preventative type of genebased therapy has led to a sharp decrease in phenylketonuria, a metabolic disorder in which the protein phenylalanine (found in artificial sweeteners) cannot break down properly, leading to severe mental retardation.

Regenerative Medicine

No amount of detection or targeted medicine can cure those conditions so genetically complex, or that accumulate to such an extent over time, that entire body systems fail. Organ transplant remains the only option, but supply, demand, compatibility, life-long monitoring, and the fragility of the patient complicate the issue. “In the last decade, the need for organ transplantation has tripled, while the amount of transplants performed has remained flat,” noted Dr. Anthony Atala of the Wake Forest Institute for Regenerative Medicine (Winston- Salem, SC). Regenerative medicine uses the patient’s own cells to create replacement organs or tissue, eliminating rejection issues.

Dr. Atala developed a process of harvesting still-functional cells from a patient and from them, fashioning a new organ. Cells are placed in a growth medium in which they are allowed to replicate. Once enough cells are available for a construct, a 3D scaffold is made in the shape and size of the organ being replaced. Cell-seeded scaffolds are then placed in an incubator mimicking conditions of a human body. Bolstered with bioreactors, cells are allowed to grow throughout the scaffold. Once the construct is complete and the cells mature, implantation takes place. The process takes four to six weeks, and the platform is absorbed harmlessly into the host’s body.

Over the past decade, Dr. Atala has successfully fashioned and implanted fully functional bladders, vascular and corpora tissue, and cartilage. Organs such as the heart or pancreas are too complex to be grown at the moment, but by repopulating them with healthy cells, the organs can be revitalized.

“You don’t want to replace a whole heart,” said Dr. Atala. “It’s a very complex organ. Heart disease is really a weakness of the muscle. One of the ways to get around that is to repopulate it with new, younger cells grown from the patient’s heart muscle.” Similarly, pancreatic beta cells, whose atrophy causes diabetes, could be replaced, leaving the pancreas and its other systems intact.

The ultimate goal of regenerative medicine is what Dr. Atala and others describe as a “universal cell.” Though still a theoretical concept, a universal cell, either synthetic or naturally occurring, would be much like a stem cell. It could be cultured to grow into any sort of tissue or organ. However, unlike stem cells, universal cells would not be recognized as foreign bodies in a recipient. It would be offthe- shelf and readily available for tissue therapies and emergencies.