AADCd Genetic Variations: Italy

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The scientific journal ′′ Brain ′′ has published a study entitled ′′ Aromatic l-amino acid decarboxylase deficiency: a patient-derived neuronal model for precision therapies ", conducted by a Scaliger University research group led by Mariarita Bertoldi, professor of Organic chemistry, together with Giada Rossignoli and Giovanni Bisello.

 

The study, which sees the collaboration of University College and Great Ormond Street Hospital London and has the financial support of the The AADC Research Trust association It provides important elements to define a new personalized therapeutic strategy for patients with AADC deficiency, a very rare serious neurometabolic genetic disease and often fatal outcome in the first years of life.

 

Read the article in UnivrMagazine: https://bit.ly/2NPE6Cv

AADC deficiency, new research by the University of Verona on this rare genetic disease
March 2021

Published on Brain the study of the research group coordinated by Mariarita Bertoldi in collaboration with University College and great Ormond Street Hospital in London

Aromatic L-amino acid decarboxylase deficiency, AADC deficiency, is a very rare and often fatal neurometabolic genetic disorder in the first years of life. To date, about 150 patients have been identified in the world but it is estimated that the global incidence of this pathology is equal to 0.112%. The disease causes the decrease or lack of the neurotransmitters dopamine and serotonin that determine severe motor, neurometabolic and developmental symptoms.

In recent days, the prestigious scientific journal Brain has published a study by the research group of the University of Verona led by Mariarita Bertoldi together with Giada Rossignoli and Giovanni Bisello that provides important elements to define a new personalized therapeutic strategy giving hope for the future of patients suffering from this disease. The research, entitled"Deficiency of the enzyme Decarboxylase of amino acids (AADC): a patient-derived neuronal model for precision therapies"was conducted in collaboration with University College and great Ormond Street Hospital in London and with the financial support of the AADC Research Trust association.

 

"Unfortunately, there is no clear correlation between the genotype of patients, the profile of diagnostic markers, the activity of the AADC enzyme and the clinical phenotype – explains Professor Bertoldi -. Topical drug treatments buffer symptoms with modest improvements. The published work is an excellent example of interdisciplinarity and aims to propose a personalized therapeutic strategy. Our biochemical contribution was the identification and structural and functional characterization of some protein variants. This research has allowed us to predict the responsiveness of some patients to the L-Dopa substrate as a therapeutic approach. Thanks to a collaboration with the prestigious University College of London, UK, Giada Rossignoli, PhD in my research group, has obtained in vitro a humanized neuronal model of AADC deficiency starting from fibroblasts of patients and mimicmed the clinical phenotype at the cellular level. A specific treatment on derived neurons restores levels of protein and its activity with refinement of neuronal maturity. The administration of L-Dopa has been shown to be effective in improving cellular parameters in a mutation-specific manner by validating the provisions of biochemical studies. The integration between biochemistry, cell biology and clinical biology is the basis of a targeted strategy to counter and treat this devastating pathology".

Thanks to this work, the properties of specific AADC mutations with validation in neurons derived from patients are further defined. "Our study has great potential in guiding personalized pharmacological strategies for the treatment of rare diseases – concludes Bertoldi -. AADC deficiency has a phenotype that mimics Parkinson's disease and could serve as a model system for wider action in pathological conditions due to aberrant levels of monoamine neurotransmitters that affect high percentages of the population".

Acknowledgements

We sincerely thank the AADC Research Trust for inspiring us to undertake this study, and our patients and their families for participating in this study. 

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