UM171 is a synthetic molecule, originally developed in Montreal, that helps multiply blood stem cells outside the body for transplantation. While probing how it works, Lund University group leader Agatheeswaran Subramaniam and doctoral student Rohit Sivaprasad found an unexpected connection to medulloblastoma, the most common malignant brain tumour in children, which affects roughly 15 to 20 children in Sweden each year.
The molecule acts through the protein KBTBD4, triggering breakdown of a cellular structure called CoREST. Mutations in the KBTBD4 gene, found in a subgroup of aggressive childhood brain tumours, produce the same breakdown, but with a crucial difference: the molecule's effect is temporary, whereas the mutations cause a lasting CoREST shortage that keeps cells trapped in a stem-cell-like state, a condition that may seed embryonal tumours. The findings are published in Cancer Gene Therapy.
A large-scale drug screen then showed that HDAC inhibitors, an existing class of medicines that modulate gene activity, counteract the effects of the KBTBD4 mutations in the team's laboratory models. Because the experiments were conducted in blood stem cells, the next step is to test whether the same drugs work in medulloblastoma tumours themselves, which are notoriously difficult to recreate in the laboratory. If they do, drug repurposing could shorten the path to new treatment options.