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Progetto prof. Festenstein
Il progetto – intitolato "Studi farmacodinamici di un istone inibitore della diacetilasi nell'atassia di Friedreich", dal costo complessivo di quasi £ 72.000,00 e della durata di 12 mesi – è stato parzialmente finanziato da AISA per un importo pari ad € 25.000,00 (circa £ 21.800,00), in collaborazione con altre associazioni europee che si occupano di promuovere la ricerca sulle atassie:
- Ataxia UK;
- Friedreich’s ataxia society Ireland:
- Association Suisse de l'Ataxie de Friedreich
Il progetto è stato finanziato nel corso del 2011 anche grazie al contributo fornito da alcune nostre sezioni.
Riportiamo di seguito una breve presentazione del progetto.
Title of Project: Pharmacodynamic studies of a histone deacetylase inhibitor in Friedreich’s ataxia
Name of Principal Applicant: Professor Richard Festenstein
Department and Institution where the work will be carried out: Imperial College Department of Medicine, London
Summary of project: Friedreich’s ataxia (FRDA) is caused by a GAA repeat expansion in the Frataxin gene causing its repression which resembles the archetypal epigenetic phenomenon of Position Effect Variegation and hence can be modulated by chromatin modifiers (Saveliev et al., 2003). We have now confirmed that a similar form of silencing occurs in cells from FRDA patients. Based on these findings histone deacteylase (HDAC) inhibitors which can overcome such silencing have been identified (Festenstein, 2006; Herman et al., 2006). We have extended this result by showing that the classical Class III HDAC inhibitor, nicotinamide, can relieve silencing in cells from patients. Nicotinamide is a vitamin and a registered drug and has been previously administered to humans with no significant ill effects (Gale et al., 2004). We will perform pharmacodynamic studies on nicotinamide in humans with FRDA to investigate whether we can upregulate Frataxin and if so, to determine an optimum dosing regimen. Nicotinamide will be administered orally following a standard drug escalation regimen and blood samples taken to measure Frataxin level and chromatin structure of the Frataxin gene. The end-point of the study is to achieve significant upregulation of Frataxin in patients providing a potential therapy for this currently untreatable condition.
Duration of grant: 12 months
Financial support awarded:
FINANCIAL DETAILS SALARY COSTS
Salary postdoc: £30,927
Employer’s costs (NI, pension): £8,986
Salary technician: £3,591
Total salaries: £43,503
Consumables:
| Plastic ware | £4,000 |
| General reagents | £4,464 |
| IMP (Investigational Medicinal product) | £20,000* |
| Sir John McMichael Centre | waived |
| Sub-total £ | 28,464 |
Total cost: £71,967
