Gene therapy for rare diseases

What are genetic diseases?

Genetic diseases are conditions caused by errors in DNA. When a disease is caused by a defect in a single gene, it is referred to as a monogenic disease. Pompe disease and Hunter syndrome are examples of monogenic diseases.

In Pompe disease, the error is located in the GAA gene. In Hunter syndrome, the defect is found in the IDS gene. In principle, monogenic diseases can be treated with gene therapy.

Learn more about Pompe disease

Learn more about Hunter syndrome

Gene therapy

In gene therapy, patients are given healthy DNA to compensate for the error in their own DNA. This healthy DNA is a correct copy of the affected gene. LentiCure focuses on treating monogenic diseases using gene therapy.

Healthy DNA can be delivered in different ways:

• In vivo: A healthy version of the gene is delivered directly to the patient, for example through an injection that targets the liver.

• Ex vivo: Cells are removed from the patient’s body and modified in the laboratory with a healthy copy of the gene. The corrected cells are then returned to the patient. An example of this approach is the modification of hematopoietic stem cells outside the patient’s body.

For gene therapy to be effective, the healthy DNA must reach the correct cells. This is achieved using vectors—delivery vehicles that transport the healthy DNA to the right location. There are different types of vectors, including inactivated viruses (known as viral vectors), polymers, liposomes, and peptides.

Lysosomal storage diseases

LentiCure focuses on rare monogenic disorders and, for now, specifically on lysosomal storage diseases. In these diseases, the lysosome does not function properly due to a missing or defective protein—an enzyme.

Learn more about lysosomal storage diseases

Lentiviral gene therapy

A specific type of viral vector is the lentiviral vector. Lentiviral vectors are derived from lentiviruses that have been modified and made safe to deliver a healthy copy of a gene. LentiCure uses lentiviral vectors to deliver a healthy gene ex vivo.

Learn more about lentiviral gene therapy

Why Gene Therapy Offers an Advantage Over Enzyme Replacement Therapy

Current enzyme replacement therapy (often abbreviated as ERT) works quite well for many patients: disease progression is significantly slowed. For some patients, the effect is so strong that they barely notice the disease anymore—except for the fact that they still need to spend several hours on an infusion every one or two weeks. Unfortunately, enzyme replacement therapy cannot reach the brain: the so-called blood–brain barrier prevents the medication from passing through. We expect our gene therapy to be able to do this, and therefore to halt the destructive disease process in the brain as well. Patients with the most severe forms of Pompe and Hunter disease also experience neurological symptoms.

Enzyme replacement therapy is very costly and, in principle, must be continued for life. The new gene therapy is also expensive, but it is a one-time treatment. We expect that, over time, this one-off cost will be roughly equivalent to one to two years of ERT costs for a patient—resulting in a substantial reduction in overall healthcare costs.