The first project revolves around the CRISPR-Cas technology, with which a mistake in the DNA can be repaired very precisely. Researchers from France, Spain and Rotterdam see exciting opportunities for patients with sickle cell disease. This is a hereditary disease of the red blood cells caused by an error in the hemoglobin protein. Hemoglobin carries oxygen from the lungs to the rest of the body.
‘You should see our plans as a kind of spelling correction’, explains research leader Sjaak Philipsen of the Department of Cell Biology at Erasmus MC. ‘In sickle cell disease, there is an error in only one of the 3 billion letters, or bases, of our genome. Our goal is to correct that abnormal letter so that the hemoglobin protein is back to normal.’
The technique for such a base correction already exists, but Philipsen and colleagues want to improve the method and test it in cultured cells from sickle cell patients. To do so, they received a grant from the European Innovation Council of nearly 4 million euros, of which 727,000 euros will go to Erasmus MC. It is an ambitious project, Philipsen acknowledges. ‘The most challenging part is to get base-correction working in patients. But ultimately that is the goal.’
In the second project, the researchers opt for an alternative approach. They are looking for compounds that promote the production of ‘baby’ hemoglobin. Before birth, red blood cells contain only baby hemoglobin. After birth, this is replaced by adult hemoglobin. In patients with sickle cell disease, the baby hemoglobin is undamaged. ‘We are going to test 130,000 compounds for their ability to stimulate the production of baby hemoglobin. We’ll select the most effective substances compounds and make variants of them that work even better’, Philipsen explains.
He expects that new, cheap, safe and effective medicines for sickle cell patients can be developed in due course with this approach. This is also an ambitious project: the new medicines must be as effective as possible, have as few side effects as possible and be safe with long-term use. The researchers have received a grant of 596,000 euros from Dutch Research Council (NWO) for this project and are working together with the European Molecular Biology Laboratory (EMBL) in Heidelberg.
Both approaches are necessary, say the researchers. Philipsen: ‘DNA correction will cure patients of sickle cell disease, but this treatment is expensive and requires a sophisticated healthcare infrastructure. A new drug will be much easier to use on a large scale. That can make all the difference for the more than 30 million sickle cell patients in low- and middle-income countries.’
About sickle cell disease
- Sickle cell disease is a hereditary disease of red blood cells. An error in the hemoglobin protein gives the red blood cells an abnormal shape.
- Patients with sickle cell disease have chronic anemia and severe pain attacks also called sickle cell crises.
- The disease can damage organs. As a result, the life expectancy of patients in the Western world is 20-30 years shorter than that of the general population. In low-income countries, where there is no good healthcare, 75% of patients die before the age of five.
- In The Netherlands, there are approximately 2000 patients with sickle cell disease and 40 to 60 babies are born with sickle cell disease every year.
- Current treatment options include anti-symptomatic drugs (antibiotics, folic acid, hydroxycarbamide), blood transfusions, and stem cell transplantation if a suitable donor can be found.
- About 600 patients (children and adults) are treated in the Sickle Cell Center of Erasmus MC. A multidisciplinary team led by pediatrician-hematologist Dr. Marjon Cnossen and internist-hematologist Dr. Anita Rijneveld provides the complex care these patients need.
- The Erasmus MC Sickle Cell Center is recognized by the Dutch Federation of University Medical Centers (NFU) and is a member of EuroBloodNet, the European reference network for rare blood diseases.