Frequently Asked Questions

the European Union defines a condition as rare when it affects less than five out o 10,000 people, so roughly less than one in 2,000 people. Rare diseases are chronic, often life-threatening and sometimes of genetic origin. Pompe disease and Hunter syndrome are life-threatening and genetic rare diseases. Pompe disease occurs in one in 40,000 live births in Europe. Hunter syndrome occurs in one in 240,000 people in Europe.

You could even say that rare diseases will become more common, because existing diseases are becoming increasingly easy to analyze. There are already 5,000 to 7,000 rare diseases. All in all, 5 to 7% of the Dutch population has a rare disease or will develop one. That is a lot. The patients and the treatment of the diseases are in danger of falling by the wayside if we do not change course.

The answer to this question can be found in the article on gene therapy in this website.

Want to know more about lentiviral gene therapy? Read the scientific articles about it.

It is a progressive, hereditary disease, that happens when there is a mistake in the DNA, in particular in the GAA gene. This mistake in the DNA results in a defect in an enzyme, acid alpha-glucosidase or GAA. This enzyme is important for the waste and recycling factory of the cell. Normally, this enzyme is involved in breaking down large sugar molecules or large carbohydrates (glycogen) into sugars that are then returned to a cell. But if this enzyme is missing or does not work well, the large sugars build up. That is why it is also called a 'glycogen storage disease'.

The accumulation of large carbohydrates has an effect on all cells and tissues of the body, but especially on the muscles. They become very weak and as a result you cannot move or breathe properly. In the most serious form of this disease, if patients are not treated, they die within the first year of life. In this form of the disease, the patients have an enlarged heart and the brain is affected. There are also slightly milder forms and then patients often end up in a wheelchair and are dependent on a ventilator for breathing.

It is a progressive, hereditary disease. Hunter syndrome happens when there is a mistake in the DNA, in particular in the IDS gene. This mistake in the DNA results in a defect in an enzyme, Iduronate 2-sulfatase or IDS. This enzyme is important for the waste and recycling factory of the cell. Normally, this enzyme is involved in breaking down large carbohydrates (mucopolysaccharides) into smaller sugars that are then returned to a cell. But if this enzyme is missing or does not work well, the carbohydrates build up. That is why it is also called a ‘storage disease'. The accumulation of large sugars has an effect on all cells and tissues of the body.

Boys and men can be affected by this condition because the IDS gene is in the X chromosome. Girls can be carriers, meaning they have one copy of the faulty gene but usually don’t show the symptoms.

There are two types of Hunter syndrome: the severe and the mild form. The characteristics differ per type and per person.

In the severe form, symptoms begin in infancy or early childhood, usually before the age of 2. The symptoms in the severe form are much more noticeable and progress quickly. Children with Hunter syndrome may lose skills they previously had, like walking or talking. These children have special facial features: a broad nose, thick lips, and large tongue. Other symptoms include breathing and heart problems, and hearing loss. Many people with the severe form may face early death, often in childhood or early adulthood.

In the mild form, children may develop normally at first, and symptoms may not appear until later in childhood (usually after age 4). The symptoms can be more gradual and less severe. They may include: mobility problems, heart problems, hearing loss, respiratory problems, and facial features but not as noticeable or disabling as in the severe form. People with the mild form might have normal life expectancy or live well into adulthood, although they may still need medical care for the symptoms.

The following sites explain where we are at the moment with our research:

Op weg naar een klinische trial voor de ziekte van Pompe - Spierfonds

https://www.hersenstichting.nl/onderzoeken-en-projecten/dichter-bij-een-behandeling-voor-de-ziekte-van-hunter/

Bringing the first treatment of the innovative lentiviral gene therapy to market is the most expensive. For the second therapy, you can already reuse a lot of knowledge, data and infrastructure, which will make that development trajectory less expensive and even more so for the following therapies. That is why it is of great importance that the first therapy we develop is not only better for the patient, but also saves healthcare costs: only then can we raise the financial resources to make it happen.

Medicines are already being given for the treatment of Pompe disease and Hunter syndrome: the so-called enzyme replacement therapy. This therapy is very expensive: hundreds of thousands of euros per patient per year. We are developing our lentiviral gene therapy with the aim of making this expensive enzyme replacement therapy completely or almost completely redundant after a single treatment. That is an enormous saving in healthcare costs.

After that, we can start working on developing gene therapies for diseases for which there is currently no treatment. It is important that we already have a lot of knowledge, data and infrastructure and have achieved savings, so that we can keep the costs of that therapy even lower.

For those diseases, we as a society often also bear a lot of costs spread over the life years of a patient to support those patients, but those costs are largely paid from other pots than the budget for medicines and treatments.

There is also a medical / scientific reason: the Erasmus MC houses the global knowledge center for Pompe disease. We can use that knowledge very well for the development of gene therapy for Pompe disease. All patients in the Netherlands with Hunter syndrome are also treated via the Erasmus MC, which makes it a logical second disease for us to develop a treatment for.

The current enzyme replacement therapy (often abbreviated to ERT: Enzyme Replacement Therapy) works quite well for many patients: the decline is significantly slowed down. For some patients, it works so well that they hardly notice they have the disease anymore – except for the fact that they have to be connected to an IV for several hours every one or two weeks. Unfortunately, what enzyme replacement therapy cannot do is reach the brain: the so-called blood-brain barrier stops the drug. The expectation is that our gene therapy can do that and therefore also stop the devastating process in the brain. Patients with the most severe forms of Pompe and Hunter also have problems with the brain.

Enzyme replacement therapy costs a lot of money every year, in principle for life. The new gene therapy also costs a lot of money, but that is a one-off expense. We expect that in the long term, these one-off costs will be about the same as one to two years of ERT costs for a patient. An enormous cost saving.

We are now preparing a clinical trial. The exact start date has not yet been determined. Because this lentiviral gene therapy is in principle a one-time treatment, our hope and expectation is that patients who participate in the trial will be treated for the rest of their lives. But of course, a clinical trial always involves a certain degree of uncertainty. A therapy may not work at all or it may turn out that (some of) the patients still need a form of enzyme replacement therapy after the gene therapy, but then less often or at a lower dosage.

Frequently Asked Questions

What is a rare disease?

Why gene therapy?

What is Pompe disease?

What is Hunter syndrome?

What research is done?

Why does LentiCure start treating these rare diseases first and not others?

Why is gene therapy better than current enzyme replacement therapy?

When will the first patients be treated?