Learning from ‘natural gene therapy’ study published in Nature Medicine

Thanks to major contributor, Professor Owen Smith, Professor of Paediatric and Adolescent Medicine, Consultant Paediatric Haematologist at Children’s Health Ireland at Crumlin,  Chief Academic Lead for Children's Hospital Group, UCD & EWOG-MDS National Coordinator for Ireland

Children with myelodysplastic syndrome (MDS) do not produce sufficient blood cells in their bone marrow and are at high risk to develop leukaemia. Twenty-five years ago, European researchers founded the EWOG-MDS to improve diagnostic procedures and therapy for these rare disorders. They started a European registry to collect clinical data and archived biomaterial in the registries’ biobanks ((opens in a new window)https://ewog-mds-saa.org).

This longstanding scientific collaboration has now given rise to astonishing discoveries. Professor Owen Smith, Professor of Paediatric and Adolescent Medicine at UCD, Consultant Haemato-oncologist at CHI (Children’s Health Ireland) and National Clinical Lead for Childhood, Adolescent & Young Adult Cancer at the NCCP (National Cancer Control Programme) has been the National Coordinator for Ireland with EWOG-MDS since its inception.

In the October 2021 issue of (opens in a new window)NATURE MEDICINE researchers from the University Children’s Hospital Freiburg, Germany, and St. Jude Children’s Hospital Memphis, USA, together with members of EWOG-MDS, report that some young patients inherit mutations in the genes SAMD9 and SAMD9L.

Cooperating closely, scientists analyzed data from the registry and found that eight percent of children with MDS had SAMD9 or SAMD9L mutations in their blood cells. That makes these mutations one of the most common causes of MDS in children.

The researchers found evidence that bone marrow stem cells did not tolerate the mutant genes well. In fact, in 61% of patients who carried a SAMD9 or SAMD9L mutation, stem cells found a method to inactivate or suppress the mutation by a process that served as natural gene therapy. In some instances, the result was a complete correction of the diseased cells, and the children were cured of their blood disease. In others, the alterations increased the child’s risk for leukemia. Some patients had blood cells with both good and bad genetic changes competing for dominance.

“Our studies lay the groundwork to explore the process in detail. We want to see how we might be able to manipulate SAMD9 and SAMD9L genes to the advantage of our patients,” said Marcin Wlodarski, MD, PhD, of St. Jude Hematology. ’Natural gene therapy’ provides us with crucial clues on how to treat and cure patients with ‘synthetic" gene therapy’ in the future" adds Charlotte Niemeyer from the EWOG-MDS study center in Freiburg.

*Taken from UCD School of Medicine*