Preliminary results from these animal models suggest development of gene transfer techniques, which represent a potentially attractive novel approach to haemostasis in MAPK Inhibitor Library patients with haemophilia and other platelet disorders. In this supplement, we discuss current prophylaxis treatment strategies for patients with haemophilia and highlight future directions for continued research. Through an improved understanding of prophylaxis in patients with haemophilia, including the potential use of bypassing agents as primary prophylaxis in those who have developed inhibitors, we aim to develop more optimal treatment
strategies that further improve the quality of life of patients. The author states that he has no interests that might be perceived as posing a conflict or bias. “
“Summary. Combined factor V (FV) and factor VIII
(FVIII) deficiency (F5F8D) is a rare autosomal recessive disorder caused by mutations in LMAN1 or MCFD2 genes which encode proteins that Proteasome activity form a complex involved in the transport of FV and FVIII from the endoplasmic reticulum to Golgi apparatus. We report two novel mutations in MCFD2 gene and one recurrent mutation in LMAN1 gene that caused combined FV and FVIII deficiency in two unrelated Tunisian Muslim families. For the first family two patients were homozygous for a new missense mutation Asp81His in exon 3 of MCFD2 and heterozygous for a second new missense mutation Val100Asp in the same exon. Replacement respectively of the hydrophilic Asp residue with hydrophobic positively charged His and of the hydrophobic neutral Val residue with the Asp residue most likely learn more disrupts the MCFD2–LMAN1 interaction, thus leading to the disease phenotype. For the second family
a reported Arg202X mutation in exon 5 in the LMAN1 gene was identified in the homozygous state. “
“LB01 Haemophilia B gene therapy study in the UK AMIT NATHWANI UCL Cancer Institute, Paul O’Gorman Building, University College London, 72 Huntley Street, London WC1E 6BT Correspondence: Amit Nathwani, UCL Cancer Institute, Paul O’Gorman Building, University College London, 72 Huntley Street, London WC1E 6BT. Tel.: +44 (0)20 7679 6225; fax: +44 (0)20 7679 6222; e-mail: [email protected] Our study differs from previous HB clinical trials with AAV vectors in three important aspects. Firstly, AAV8 pseudotyped vectors will be used instead of AAV2 primarily because of the substantially lower prevalence of pre-existing humoral immunity to this AAV serotype in humans. The second difference relates to the use of a vector containing a self complementary genome which, is more potent than concentional single stranded AAV vectors and offers a unique opportunity to mediate efficient therapeutic gene transfer potentially at a low dose of vector.