世界血友病同盟(World Federation of Hemophilia,WFH)于2022年10月发布了新的年度血友病全球报告(Annual Global Survey,AGS)(以下简称AGS 2022),提出了新的工作目标。在2025年前,提高识别并诊断遗传性出血性疾病能力,包括:在原有基础...世界血友病同盟(World Federation of Hemophilia,WFH)于2022年10月发布了新的年度血友病全球报告(Annual Global Survey,AGS)(以下简称AGS 2022),提出了新的工作目标。在2025年前,提高识别并诊断遗传性出血性疾病能力,包括:在原有基础性上,提高25%的血友病确诊率和14%的血管性血友病(von Willebrand disease,vWD)患者确诊率;提供合适的护理和治疗,特别是要提高25%的18岁以下重型血友病患者预防治疗率,继续每年至少为20000例患者提供WFH人道主义援助。AGS 2022预估了全球的血友病年平均患病率:血友病A(hemophilia A,HA)为17.1/10万(男性),其中重型HA为6.0/10万(男性);血友病B(hemophilia B,HB)为3.8/10万(男性),其中重型HB为1.1/10万男性。根据世界人口(79亿,40亿男性),预计全球血友病患病率在10.6/10万左右,预计全球有血友病患者830895例,其中约282266例为重型患者。我国的血友病患病率在(2.73~3.09)/10万,低于全球水平。同时,AGS 2022提示,全球女性血友病患者有11700例,女性血友病占血友病患者总人数的5%;女性vWD患者有54066例,占vWD总人数的56%,女性其他出血性疾病有34370例,提示vWD是女性最常见的出血性疾病。我国的HA患者共27689例,其中0~4岁占4%,5~13岁占21%,14~18岁占12%,19~44岁占43%,45岁以上占16%,年龄不确定者占4%。相对于中低收入国家,高收入国家对于轻型血友病的确诊率高(男性40%比12%;女性86%比23%),不确定性患者比例少,而低收入国家的血友病患者早逝风险很大。经济发达地区的艾美赛珠单抗预防治疗使用显著高于我国。我国相较于欧美国家在血友病及其他出血性疾病患者的诊断及治疗方面还有较大差距,临床医务工作者需提高对血友病及其他出血性疾病的认识并不断提高诊断和治疗能力。展开更多
A mutant human factor IX with arginine at 338 residual changed to alanine (hFIXR338A) by site-directed mutagenesis was introduced into AAV vectors, and a recombinant adeno-associ-ated viral vector containing hFIXR338A...A mutant human factor IX with arginine at 338 residual changed to alanine (hFIXR338A) by site-directed mutagenesis was introduced into AAV vectors, and a recombinant adeno-associ-ated viral vector containing hFIXR338A, prepared by rHSV/AAV hybrid helper virus system, was directly introduced to the hind leg muscle of factor IX knock out mice. The expression and the biological activity of human factor IX mutant, hFIXR338A, and the immune response against it in the treated mice were assayed and detected. The results showed that (i) the high-level expression of human factor IX mutant protein, hFIXR338A, has been detected in rAAV-hFIXR338A treated hemophilia B mice and lasted more than 15 weeks; (ii) the clotting activity of hFIXR338A in plasma is 34.2%± 5.23%, which is remarkably higher than that of (14.27%±3.4%) of wild type hFIX treated mice in the activated partial thromboplastin assay; (iii) immune response against factor IX R338A was absent, with no factor IX mutant protein (hFIXR338A) inhibitors development in the treated mice; and (iv) no local or systemic side-effects and toxicity associated with the gene transfer were found. It demonstrated the potential use of treating hemophilia B by recombinant adeho-associated viral vectors with mutant hFIXR338A gene, an alternative strategy for hemophilia B gene therapy to wild-type human factor IX.展开更多
基金the State High Technology Development Program (Grant No.Z20-02-01), Shanghai Post-doctoral Fellowship Foundation the National "863" High-Tech Program+1 种基金 the National Natural Science Foundation of China (Grant No. 39880019) Fok Ying Tung Foundation (Gra
文摘A mutant human factor IX with arginine at 338 residual changed to alanine (hFIXR338A) by site-directed mutagenesis was introduced into AAV vectors, and a recombinant adeno-associ-ated viral vector containing hFIXR338A, prepared by rHSV/AAV hybrid helper virus system, was directly introduced to the hind leg muscle of factor IX knock out mice. The expression and the biological activity of human factor IX mutant, hFIXR338A, and the immune response against it in the treated mice were assayed and detected. The results showed that (i) the high-level expression of human factor IX mutant protein, hFIXR338A, has been detected in rAAV-hFIXR338A treated hemophilia B mice and lasted more than 15 weeks; (ii) the clotting activity of hFIXR338A in plasma is 34.2%± 5.23%, which is remarkably higher than that of (14.27%±3.4%) of wild type hFIX treated mice in the activated partial thromboplastin assay; (iii) immune response against factor IX R338A was absent, with no factor IX mutant protein (hFIXR338A) inhibitors development in the treated mice; and (iv) no local or systemic side-effects and toxicity associated with the gene transfer were found. It demonstrated the potential use of treating hemophilia B by recombinant adeho-associated viral vectors with mutant hFIXR338A gene, an alternative strategy for hemophilia B gene therapy to wild-type human factor IX.
