Gene therapy
Gene therapy is a treatment in which we try to treat disease by working with the body’s genes.
Gene therapy: treatment using the body’s own building blocks
Gene therapy is a treatment in which genetic material is changed, added, or regulated to treat disease. It is not only inherited diseases that can be treated this way—certain cancers and chronic diseases are also treated with gene therapy today.
Genes can be described as the body’s small instructions that tell cells how to function. If there is an error in an instruction, it can lead to disease. With gene therapy, for example, the goal is to give the body a new, functioning instruction or help the cells do what they cannot do on their own.
Gene therapies work in different ways
Some replace a gene that does not work. Others turn off a gene that causes harm. Still others edit the body’s own genes or equip cells with new properties.
An important regulatory principle
If a treatment involves both cells or tissue and genetic modification, it is always classified as gene therapy. This applies, for example, to CAR-T treatments, in which the patient’s own immune cells are genetically modified in the laboratory.
Safety and control
Gene therapy can have long-lasting effects, potentially lifelong, because the treatment often permanently changes the way cells function. That is one of the reasons why development, approval, and follow-up require significant professional and regulatory attention.
There must be control over the entire treatment chain: the genetic material, the method by which the genetic material enters the cells, manufacturing, quality, safety, and clinical follow-up.
For some gene therapies, patients are followed for a long time after treatment. This is about both seeing how long the effect lasts and detecting any side effects over time.
Two ways to deliver gene therapy
Gene therapy can be carried out in two different ways, depending on whether the treatment takes place inside or outside the body.
In vivo gene therapy: Given directly to the patient. The genetic material is introduced into the body, for example as an infusion in the blood or as an injection into a specific tissue.
Ex vivo gene therapy: Takes place outside the body. First, cells are taken from the patient (or a donor), genetically modified in the laboratory, and then returned to the patient.
To get genetic material into the cells, a vector is often used. A vector is a kind of transport system. It can, for example, be a virus that has been modified so it does not cause disease, but can still deliver genetic material into the cells.
Examples of gene therapy
Gene therapy is already part of several treatments in Denmark. Here you can see examples of how genes can be used to treat disease.
Gene therapy can help with inherited vision loss (RPE65)
Some rare, inherited retinal diseases can cause gradual vision loss. In some patients, the disease is due to mutations in the RPE65 gene, and if there are still enough functioning cells left in the retina, gene therapy may be an option in some cases.
The treatment is given as an injection directly under the retina, where a functioning copy of the gene is delivered to the cells in the eye. The goal is not to provide "new, normal vision", but to preserve functional vision—such as the ability to orient oneself and move in dim lighting..
An example is Luxturna (voretigene neparvovec), which can be used for this patient group when the criteria are met. The Danish Medicines Council has recommended Luxturna as a possible standard treatment for patients with inherited RPE65-related retinal dystrophy.
Gene therapy can slow severe muscle weakness
Spinal muscular atrophy (SMA) is a serious inherited disease in which the nerve cells that control the muscles weaken. This can lead to muscle weakness and, in severe cases, make it difficult to move, swallow, and breathe.
With gene therapy, in some cases it is possible to deliver the body a functioning copy of the SMN1 gene, so the body can produce the protein that the nerve cells need. For some patients, this can mean that the progression of the disease is slowed. In studies, the treatment has also reduced the need for permanent ventilator support.
An example is Zolgensma (onasemnogene abeparvovec), which is approved in the EU for certain patients with 5q SMA and mutations in the SMN1 gene. Zolgensma is included in the Danish Medicines Council’s drug recommendation for children with SMA type 1 and presymptomatic infants.
Treatment can reduce bleeding in hemophilia B
Hemophilia B is an inherited bleeding disorder in which the body has too little of the protein factor IX, which is necessary for blood to clot. When the body lacks factor IX, bleeding can therefore last longer and be more difficult to stop.
Here, gene therapy can enable liver cells to produce more factor IX themselves. The treatment is given once as an infusion. For some patients, this can mean fewer bleeding episodes and potentially reduce the need for regular factor IX infusions. However, it may take a few weeks before the effect becomes apparent, and results can vary from patient to patient.
Hemgenix (etranacogene dezaparvovec) is approved for adults with severe or moderately severe hemophilia B.. The Danish Medicines Council has recommended Hemgenix for adult patients with hemophilia B (congenital factor IX deficiency) in severe and moderately severe degrees.
CAR-T treatments - examples of genetically modified cell therapy
When the patient’s own immune cells are used against cancer
CAR-T is used for certain types of blood cancer. The treatment works by using the patient’s own immune cells to fight the cancer.
First, some immune cells are taken out of the patient’s blood. In the laboratory, the cells are modified so they can recognize cancer cells better. Then the patient receives the cells back into the body.
The modified immune cells can now find and attack the cancer cells they are designed to target. CAR-T is a special type of treatment because it is based on both cells and genes. It consists of living immune cells from the patient themselves. Therefore, it is a cell therapy. At the same time, the cells are genetically modified in the laboratory so they gain a new ability: they can recognize and attack specific cancer cells. That is why CAR-T is also considered gene therapy.
The treatment is manufactured individually based on the patient’s own white blood cells.
Examples include Yescarta (axicabtagene ciloleucel), Kymriah (tisagenlecleucel), Breyanzi (lisocabtagene maraleucel), and Carvykti (ciltacabtagene autoleucel), which are used for different types of blood cancer (leukemia (B-ALL), some types of B-cell lymphoma, and bone marrow cancer (multiple myeloma). All CAR-T treatments are recommended by the Danish Medicines Council for selected indications.The treatment is given in specialized departments because it can cause strong reactions from the immune system. For example, some patients may experience a serious inflammatory reaction in the body called cytokine release syndrome (CRS). Side effects can also occur from the nervous system. Therefore, the patient must be monitored closely during and after treatment.
Sources:
Axicabtagene ciloleucel (Yescarta) - Diffuse large B-cell lymphoma, 2nd line
Axicabtagene ciloleucel (Yescarta) - Diffuse large B-cell lymphoma, 3rd line
Lisocabtagene maraleucel (Breyanzi) - Diffuse large B-cell lymphoma (DLBCL), 2nd line
Lisocabtagene maraleucel (Breyanzi) - Diffuse large B-cell lymphoma (DLBCL), 3rd line
Tisagenlecleucel (Kymriah) - Acute lymphoblastic leukemia
Ciltacabtagene autoleucel (Carvykti) - Bone marrow cancer (RRMM)
Explore the other ATMPs
Learn more about how cell therapy and tissue therapy differ from gene therapy.
What is ATMP?
ATMP stands for Advanced Therapy Medicinal Products and is a new type of advanced medicine that uses the body’s own building blocks - genes, cells, and tissue - to repair or change what is not working.
It opens up new possibilities for treating serious diseases- also diseases where there were previously few or no treatment options. That is why ATMP is changing the way we treat some diseases.
