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AADC PhD Project Update
13 January 2010

We are happy to report that this year sees the successful completion of The AADC Research Trust’s first fully funded 3 year PhD Project titled, ‘Neurochemical Consequences of Aromatic L-Amino Acid Decarboxylase Deficiency - Implications for Disease Progression and Treatment’. 

Below is a basic update relating to the significant project provided by our dedicated PhD student George Allen.  We very much look forward to reviewing his final thesis in October 2010.

PhD Project Update

“The overall aim of our study is to produce models of AADC deficiency in brain cells and then to study the changes in the biochemistry of these cells.  We have developed models of AADC deficiency in two of the main cell types found in the brain, nerve cells and glial cells.  Using these types of cells we have recently made two key findings which could be important for our understanding of AADC deficiency and its treatment:

1. The chemical L-dopa is used by AADC to make dopamine, however in AADC deficiency much less dopamine is produced and consequently L-dopa accumulates in the brains of AADC deficient patients.  Our AADC deficient cells seem to have an altered response to L-dopa.  Cells without AADC deficiency respond to L-dopa by producing a protective chemical called glutathione.  However our AADC deficient cells produce far less glutathione in response to L-dopa.  This could suggest an increased vulnerability of AADC deficient cells to toxic chemicals.  However we are currently carrying out further work to establish how this response comes about and what the consequences may be for patients with AADC deficiency.
   
2. Vitamin B₆ either as pyridoxine or pyridoxal 5’-phosphate is a current treatment for many, but not all, patients with AADC deficiency.  Vitamin B₆ in its active form is needed by AADC to make dopamine and serotonin.  We have been investigating how vitamin B₆ affects the AADC enzyme.  We have found that reduced levels of vitamin B₆ can lead to a loss of AADC enzyme in our cells.  This finding indicates that vitamin B₆ is not only required for AADC activity but is also needed to maintain the overall levels of AADC enzyme.  Therefore this could suggest that vitamin B₆ treatment in patients may help to maintain their residual AADC levels and prevent further decreases in activity.”