Duchenne muscular dystrophy is a genetic disorder caused by a variant in the gene that codes for the protein dystrophin. Dystrophin is important for proper muscle function. In Duchenne, the dystrophin gene is dysfunctional and produces little to no dystrophin. This causes muscle cells to become easily damaged leading to loss of muscle. When the heart and lung muscles are involved, this can lead to life-threatening complications. While corticosteroids, physical therapy and care can improve quality of life, they cannot stop or reverse muscle loss.
Gene therapy is being developed as a therapy option to treat Duchenne. There are different types of gene therapy, but they all have the same goal – to change the disease progression. This can be done by:
- Replacing the dysfunctional gene with a functional copy;
- Correcting the disease-causing variant in the gene; or
- Introducing a new or modified gene that can help treat the disease.
Gene therapy has three important components:
- The transgene which is the genetic material being delivered.
- The vector which carries the transgene into cells. Vectors are usually inactive viruses that will not cause an infection.
- The promoter which turns the transgene on in specific tissue(s). For example, a functioning copy of the dystrophin gene may be carried by an adeno-associated virus and turned on by muscle and/or heart-specific promoters.
Like all therapies, gene therapy has limitations.
- First, while it can be used to slow down disease progression or potentially improve function, it isn’t a cure.
- How long the benefits last could vary from person to person and depending on the type of gene therapy used.
- The treatment’s effectiveness may depend on the person’s age and disease stage.
- Unfortunately not everyone is eligible to receive gene therapy because it wouldn’t be safe or effective for them.
- For example, someone who has pre-existing antibodies against the vector cannot receive gene therapy because those antibodies could limit the effectiveness of the therapy and pose safety risks from an immune response.
- For similar reasons, patients cannot be re-dosed because their body will produce a significant number of antibodies after the initial delivery, so gene therapy is currently a one-time treatment .
- Finally, it is possible that a serious immune response could lead to organ failure or death.
Researchers are working hard to overcome these limitations and to make gene therapy more safe and effective. In addition to exploring different vectors, strategies to suppress the immune response are being studied.
By limiting the immune response, people with pre-existing antibodies or antibodies developed as a result of a previous gene therapy may be able to receive gene therapy in the future.
