Researchers at the Leiden University Medical Centre (LUMC) have successfully used stem cell gene therapy to treat a baby with the severe congenital immune disorder SCID. An important milestone: it is the first time stem cell gene therapy of Dutch origin is administered to a patient, and also the first time it is used to treat this particular form of SCID worldwide. The treatment was effective and the patient is doing well.
The treated patient is a baby of only a few months old who suffers from SCID. Due to a DNA error in blood stem cells, SCID patients do not produce immune cells and the body cannot defend itself against infections. Stem cell gene therapy can repair this error. ‘The corrected stem cells grew into a functioning immune system in the patient’s body,’ says Arjan Lankester, Professor of Pediatrics and Stem Cell Transplantation. ‘The baby has endured the treatment without any problems and their immune system responds well to the usual vaccinations for newborns. A fantastic result.’
Three months after birth, stem cells were taken from the patient. Subsequently, a good copy of the gene, in this case the RAG1 gene, was inserted into the DNA of these cells. ‘For this we use a crippled virus,’ explains Frank Staal, Professor of Stem Cell Biology. ‘We only use the property of the virus to build its own genome in the DNA of its host, but remove all other properties. The virus is therefore just the wheelbarrow that brings the gene to the right place.’ Repaired cells were then transferred back into the patient, who was allowed to leave the hospital within a month. Staal and Lankester expect the patient will be cured for life with this complex, but one-time treatment.
Your own donor
Without treatment, children with SCID often die before the age of one. However, the current treatment, namely stem cell transplantation, has a number of disadvantages. For example, a good donor isn’t always available and transplantation with cells from another person also bears risks. ‘Because in stem cell gene therapy the patient is his or her own donor, we circumvent these problems,’ says Lankester. Further research must show whether this therapy will become the new standard for SCID in the future.
Stem cell gene therapy production requires a special laboratory. LUMC is one of the few hospitals in the Netherlands that has a licence to genetically modify cell products. ‘This means that we are not dependent on the pharmaceutical industry,’ says Staal, ‘which allows us to reduce the costs of the therapy to some extent.’ However, like other gene therapies, this treatment is still very expensive. ‘Since the therapy is still being used for research purposes, it does not cost the patient anything. But the price tag remains unclear for the long term.’ Staal recently received a grant to study the matter. ‘Our aim is to establish methods on how society can deal best with these therapies. For example, with reimbursement guidelines for policymakers.’
Ups and downs
Lankester, Staal and other LUMC colleagues have been working on the stem gene therapy for RAG1-SCID for 15 years. ‘The process had many ups and downs,’ says Staal. ‘Both in terms of developing the therapy in the lab and also the paperwork to obtain permission for use in patients.’ It was an emotional moment when it became clear that the therapy worked. ‘It is fantastic to see that we have been able to help a patient,’ says Lankester.
The ultimate goal is to make this stem cell gene therapy available to patients from all over Europe. Lankester: ‘Our motto is: the cells travel, not the patient. That way, patients and their families, who are already going through a hard time, don’t have to move abroad for a few months. This is sometimes what happens with patients suffering from other forms of SCID’. Staal and Lankester are now working to complete the paperwork to tackle this. ‘Hopefully we will be able to help more patients this way,’ Lankester concludes.