Zavesca uptake into the brain

Funds raised by two families with children with neuronopathic Gaucher disease have been awarded to support work being undertaken at Kings College to complete a study on Zavesca uptake into the brain. Dr David Begley from Kings College, London reports on this study –

‘We are delighted that the Gauchers Association has agreed to provide support for this work which has enabled Dr Larisa Mihoreanu, who works in my blood-brain barrier research group at Kings, to complete a study of the mechanism of brain penetration by this substrate reducing drug.
  Although previous studies have suggested that Zavesca does enter the brain from an oral dose, surprisingly, the mechanism of brain penetration had not been investigated. The current study has produced the unexpected finding that although Zavesca does enter the brain, it does so much more slowly than would be predicted from a study of its chemical structure. Also using a human blood-brain barrier cell line the research has shown that Zavesca can concentrate inside the cells of the barrier and once inside the cells leaves more slowly than it entered. This retention in the cells may be due to a  mechanism referred to as ion trapping and this is being investigated further.
  The current study is important because once the mechanism of cell uptake and brain entry of Zavesca is fully understood, then new second generation substrate reduction therapies, with a better and more efficient brain penetration, can be designed and developed by using the knowledge to guide the medicinal chemists.’