Acute pancreatitis is highly inflammatory pancreatic disease with no currently available specific treatment. It becomes a life-threatening complication caused by the anti-leukemic drug Asparaginase that is widely used as an effective treatment of childhood acute lymphoblastic leukaemia (ALL). Once children develop acute pancreatitis they cannot receive any more Asparaginase. Without Asparaginase treatments, children with leukaemia have very poor prognosis.
Energy supplements protect pancreas from side effects of Asparaginase
Dr Julia Gerasimenko
2 January 2019
In the recent publication (Peng et al, J Clin Invest 2018) the team has reported in detail the mechanism of Asparaginase-induced acute pancreatitis (AAP), including abnormal intracellular calcium signalling, loss of intracellular energy, necrotic cell death and inflammation. They have also established that a natural substance galactose can effectively protect from AAP in vitro and in vivo. Based on these data, the team proposed that galactose feeding can be used in combination with Asparaginase treatments for children with leukaemia.
Team will use recently developed models of AAP to test and optimise galactose feeding protocols. This will allow them to develop safer and more effective treatments for children with leukaemia.
Use of natural substance galactose as a supplement for very powerful and highly successful anti-leukaemia drugs based on Asparaginase will allow to minimise their side effects and provide potential improvements to future treatments of the childhood leukaemia.
Dr Julia Gerasimenko is one of the leading scientists in the UK working on acute pancreatitis. Together with Dr Oleg Gerasimenko they made the important discovery (Cell,1995) cited more than 331 times (Web of Science) about fundamental mechanism of calcium signalling.
Oleg Gerasimenko is a member of the Editorial board of Pflügers Archiv–Eur JPhysiol. JG is a Faculty Member (F1000-Gastrointestinal-Physiology). Oleg Gerasimenko and Julia Gerasimenko have an excellent track record in researching AP and have made significant progress characterizing the pathological effects. The most important findings, published in Journal of Clinical Investigation (2018), PNAS (2009, 2011, 2013) and Current Biology 2012 clarified the molecular mechanisms responsible for AP initiation.
Dr Sujith Samarasinghe is Consultant Paediatric Haematologist at Great Ormond Street Hospital in London. He is a key member of the national leukaemia toxicity group and has worked on defining toxicities for UKALL 2011, with a view to developing strategies to reduce their incidence.
Recently, all three applicants published together studies exploring the molecular mechanism underlying AP induced as a side-effect of Asparaginase treatment of ALL and therefore have the ability to make significant progress in the proposed grant period.