Oleg Gerasimenko
Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK
Title: Galactose can reduce side effects of Asparaginase-based drugs for childhood ALL
Biography
Biography: Oleg Gerasimenko
Abstract
Asparaginase-based drugs are very successful against childhood acute lymphoblastic leukaemia (ALL), however, they can induce Acute pancreatitis (AP) as a side effect and force clinicians to discontinue the treatments. AP is a frequent human disease with a substantial mortality with no specific therapy. Previous investigations into the mechanisms of AP established that intracellular ATP loss is a crucial factor leading to calcium overload and necrosis. We have recently reported that glucose metabolism is severely inhibited under AP conditions due to inhibition of hexokinases. ATP loss and calcium exacerbate each other and lead to necrosis. We have found that, replacing or supplementing glucose with galactose has markedly reduced the loss of ATP, calcium overload and subsequent necrosis in vitro. Galactose as an oral supplement has effectively protected against AP in two different mouse models of AP. In both cases, galactose has markedly reduced pancreatic histology scores, acinar necrosis and inflammation. We suggest that galactose oral supplement may be used to protect against AP and therefore improve efficacy of the childhood ALL treatments.