Outline Proposal for AADC Trust PhD Studentship

Currently, at this time, it is virtually impossible to secure research funding for further studies into such disorders as AADC, from any conceivable source.  Therefore, due to the important nature of such studies we are applying to The AADC Research Trust for its support in funding a PhD studentship.  It is hoped that the three year term of concentrated studies will identify and evaluate potential neurotoxic mechanisms relevant to AADC -Aromatic Amino Acid Decarboxylase Deficiency

AADC deficiency is associated with a range of clinical features including severe developmental delay, myoclonic jerks, occulogyric crises, gastrointestinal disorders and limb dystonia.  Whilst treatment with dopamine agonists, vitamin B6 and monoamine oxidase inhibitors can be beneficial, it is clear that clinical outcome can be very poor with many affected children still exhibiting a wide range of neurological disabilities.

The hypothesis that we wish to pursue is that from an early stage, the brain of an AADC deficient patient is persistently exposed to 5-hydroxytryptophan which, either directly or indirectly, is toxic towards brain cells. Consequently, characterisation of toxic metabolites that accumulate in AADC deficiency along with the elucidation of their mode of action will lead to a greater understanding of the pathogenesis of this disorder and lead to proposed new treatment strategies.

Simon Heales PhD