PhD defence: Trine Rasmussen

On Friday 4 September at 14:00, Trine Rasmussen defends her PhD dissertation entitled “Reshaping systemic and central nervous system methotrexate exposure with early glucarpidase rescue”.

Methotrexate plays an important role in the treatment of selected cancers involving the central nervous system, but a relatively small fraction of the drug crosses  from the bloodstream into the central nervous system. It is therefore administered in high doses, which may also increase the risk of side effects. A new PhD project at Aarhus University’s Faculty of Health has investigated a strategy combining a higher dose of methotrexate with planned early administration of glucarpidase, an enzyme that rapidly breaks down methotrexate in the blood. 

The project used a pig model in which methotrexate was measured in blood, cerebrospinal fluid and brain tissue. The aim was to investigate whether a higher dose could increase methotrexate  concentrations in the central nervous system and thereby potentially improve treatment, while subsequent glucarpidase administration could reduce the length of time the rest of the body is exposed to the drug. The project also explored early biochemical changes in the cerebrospinal fluid associated with the treatment. 

The findings of this preclinical study provide new insight into how methotrexate exposure in the blood and central nervous system can be altered by combining dose escalation with planned early glucarpidase-mediated breakdown of methotrexate in the blood. This knowledge may provide a basis for future studies examining whether the strategy could be used to improve treatment and reduce adverse effects in patients.

The summary is written by the PhD student.

The defence is public and takes place in C114-103, Aarhus University Hospital. Please see the press release for more information. 

Contact

PhD student Trine Rasmussen
Mail: tras@clin.au.dk 
Phone: 60706431

Read full press release