Gene therapy aims to treat the underlying genetic cause of a disease rather than only the symptoms. It involves the delivery of properly functioning DNA into a patient’s genetic material to correct an underlying genetic problem. The properly functioning DNA can modify or manipulate genes in the hopes that doing so will treat or cure the disease caused by the genetic problem. Gene therapy can, for instance, replace an improperly functioning gene with a properly functioning version, inactivate a gene that is malfunctioning, or activate a gene to help fight a disease. The properly functioning genes can be introduced into the patient through a variety of means called “vectors,” including plasmid DNA or harmless viruses or bacteria and can be administered in a variety of ways, depending on the genes at issue and the tissue targeted. The FDA has approved multiple gene therapy products for treatment of cancers or other (often rare) disease indications, and the benefits of such treatments can be truly astounding. A new method of delivering the therapy — directly into the brain — appears to be a promising method for those with certain brain disorders.
A recent article by Laura Ungar of the Associated Press describes the benefits that a therapy infused directly into the brain has had for some children with AADC deficiency — an extremely rare, fatal genetic disorder that leads to a severe deficiency in neurotransmitters, which are chemical messengers our bodies need for basic functioning. The treatment, called Upstaza, which was developed by PTC Therapeutics, uses a viral vector to deliver a working version of the dopa decarboxylase (DDC) gene directly to the brain through a minimally invasive surgery in which a thin tube is inserted through a hole in the skull. The results can be remarkable. One child received the treatment when she was only 18 months old, and its positive effects were so dramatic that the child’s parents dubbed the treatment day “reborn day.” Another child who received the treatment just before her fifth birthday was able to hold her head up for the first time, and within seven months she was able to sit up on her own. Formal clinical studies have demonstrated that most of the patients achieved physical milestones (such as ability to control head movement or sit unassisted) that untreated patients could not perform.
The research, development, and clinical trials for gene therapies come at enormous costs, which is sometimes reflected in the cost of the treatments. Ungar reported that the one-time treatment cost for Upstaza is more than $3 million in Europe, where it received marketing authorization in July 2022. A gene therapy treatment called Hemegenix, first cleared by the FDA in November 2022 to treat Hemophilia B, has been reported to cost $3.5 million per patient.
One factor that may affect the price of these treatments is the risk of product liability claims arising from complications occurring during clinical trials. Claimants may contend that they were misled regarding the safety of the treatment and would not have participated in the study if they had been given more or different information. Such claims can be of significant concern for both sponsors and investigators despite the use of detailed informed consent processes and documentation noting the experimental nature of the treatments at that early stage. While the treatments are not without risks for the treatments’ developers or the patients who receive them, the treatments can provide truly miraculous benefits for patients, and it is exciting to see what scientific ingenuity built on decades of research and incremental advances will deliver next.
