The University of Siena's Role in DevelopAKUre

Our research group is led by Prof. Annalisa Santucci and is located within the University of Siena, Department of Biotechnology, Chemistry and Pharmacy. We are one of the three Academic members of the DevelopAKUre Consortium. We have great expertise in the study of proteins related to microorganisms (such as the pathogens Helicobacter pylori and Neisseria meningitidis, but also the well-known yeast Saccharomyces cerevisiae) and human diseases, including rare ones (gastric cancer, pancreatic cancer, osteosarcoma, osteoarthritis, Lesch-Nyhan syndrome and alkaptonuria, or AKU). In the last years, we developed specific biochemical, structural biology, bioinformatics, and proteomic/post-genomic skills and platforms for the study of AKU and we were able to provide novel insights into AKU physiopathology. Access to such molecular technologies are crucial to understand AKU and to evaluate the efficacy of therapeutic approaches. Research in AKU in Siena dates back 2008, thanks also to a collaboration with the University of Liverpool and a fruitful student exchange programme. Since then, Siena has emerged as the Italian centre for the study of AKU. This is due to joint efforts from us as scientists, investigating the disease at the molecular level, rheumatologists of Siena Hospital, and the Italian AKU patients Association, aimAKU. Besides our laboratory routine, we are also constantly committed to raising awareness of AKU and disseminating AKU related information. This means not only scientific publications and meetings, but also keeping in touch with doctors, patients and caregivers. Last September we held here in Siena the first Italian AKU meeting, which gathered together scientists, doctors and patients from different regions. 

 We moved our first steps in the study of AKU by setting up and studying experimental models to reproduce under tightly controlled laboratory conditions what happens in vivo in AKU sufferers. Our models were first based on ‘healthy’ human cells and tissues that were treated exogenously with homogentisic acid (HGA), the metabolite that accumulates in AKU. Then, we further validated our results in several patients’ samples. Our main findings were that oxidative stress generated by HGA and its metabolites, inflammation and amyloidosis are events strictly correlated with the production and deposition of the ochronotic pigments in alkaptonuric tissues. For this reason, within the DevelopAKUre programme we aim at investigating the levels of various markers related to inflammation and oxidative stress in AKU patients’ blood samples. This will allow us to understand if the treatment with nitisinone can modify such parameters and, in turn, decrease their deleterious effects in AKU patients. We truly hope that our research would allow a better understanding of AKU and nitisinone.



Welcome To DevelopAKUre

DevelopAKUre is a series of major international clinical trials, run by a consortium of 12 European partners. It aims to study a potential new drug, called nitisinone, and assess its potential effectiveness in treating the rare disease, alkaptonuria (AKU).

DevelopAKUre is co-funded by a grant from the European Commission. This website is run by a UK patient group, the AKU Society. Learn more about AKU on the AKU Society's What is AKU page.


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