Babies who are born without a functioning immune system usually receive a stem cell transplant. An international research team headed by the Leiden University Medical Centre (LUMC) is granted 6 million euro from the European Horizon 2020 programme for their research into a promising alternative: the correction of the error in the DNA.
Children with the rare congenital birth defect severe combined immunodeficiency syndrome (SCID) do not have a functioning immune system. This is because of an error in the DNA. The children are enormously susceptible to life-threatening infections and, without treatment, they will die before they turn one year old. The standard treatment is a stem cell transplant. “But this is not the ideal solution for all children”, according to Arjan Lankester, Professor of Paediatrics and Stem Cell Transplantation.
Especially for babies for whom a suitable donor is not available, the result of a stem cell transplant is often not optimal. “In that situation it is like you replace a defective Peugeot engine with a Volvo engine you happen to have at the back of your garage. Somehow it works, but the car no longer runs smoothly. You’d rather replace the defective part of the Peugeot engine.” And that is precisely the approach of the study for which he and his colleague Frank Staal, Professor in Molecular Stem Cell Biology of the department of Immunohematology and Blood Transfusion have received the European subsidy of 6 million euro. The pharmacy of the hospital and the department of Medical Decision-Making also participate in the research.
Healthy copy of a weakened virus
In cooperation with a number of prominent paediatric transplant centres in Europe the researchers are tackling the core of the problem by correcting the DNA error. “We apply gene therapy: we use a weakened virus to add a healthy copy of the defective gene to the DNA of the own stem cells of children with SCID”, Staal explains. When these cells are given back to the patients, it should result in a healthy immune system. “That this can be done in our laboratory, is to a large extent the result of the efforts of our senior-researcher Karin-Pike Overzet. She is essential for our gene therapy research”, according to Staal.
Compared to a stem cell transplant gene therapy has more advantages in the opinion of the researchers. “Because we use the body’s own stem cells, we do not have to deal with complications as a result of a non-matching donor and graft-versus-host disease, in which case the new immune cells attack the body of the receiver”, Lankester explains.
What makes their study unique according to the LUMC researchers is its set-up. “We cooperate with all European experts in the field of gene therapy and stem cell transplant”, according to Lankester. More than one third of the 6 million euro goes to the LUMC, because that is where Lankester and Staal coordinate the study. “Stem cells of foreign patients are collected in their own hospitals, processed in our laboratory and subsequently returned to the partners in Europe. So we do not let the patient travel but the therapy.”
According to Staal this promising study fits in well with the long-established Leiden tradition of treatment for rare diseases, such as SCID. In the 1960’s LUMC professors created the basis for this research field and since then their successors have been in the vanguard. In 2012 Staal’s research group received a 3 million euro subsidy from ZonMw and in 2015 a one million euro subsidy from the European Horizon 2020 programme for SCID gene therapy. “This money prepared us well for the study we are now starting up”, according to Staal.