Study of gene therapy of cardiac Fabry disease

心脏病法布里病的基因治疗研究

• 批准号: 08457214
• 负责人: KANZAKI Tamotsu
• 金额: $ 4.35万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457214/
• 关键词: Fabry disease; alpha-galactosidase; left ventricular hypertrophy; gene mutation; 心ファブリー; ベクター; 遺伝子治療

As basic research for genetic therapy of cardiac Fabry disease, it is imprtant to select suitable target cells and vectors. We will assess endotheral cells of small vesels and capillary and other oragn cells as target cells. Before basic study of genetic therapy we have to clarify the phenotype and genotype in Fabry disease including in atypical type of Fabry disease which manifestaions limited to the heart. The atypical Fabry disease was named cardiac Fabry disease by us. We deteced cardiac Fabry disease of three percent among male patients with left ventricular hypertrophy. They did not have angiokeratoma, hypohidrosis, acroparesthesias, or corneal opacities. They had new mutations of A20P,E66Q,and M296I by gene analysis. We tried to find undiagnosed patients with Fabry disease among male patients undergoing chronic hemodialysis by measuring plasma alpha-galactosidase. Six of the 514 male patients were found as having Fabry disease, and they had no angiokeratoma except one. By gene analysis new mutations of A97V and G373D were detected. The phenotype and genotype of these Fabry disease who were newly found in Kagoshima and Miazaki Prefectures were different from those of classical Fabry disese. We think that the genotype and phenotype should be clarified in the futher study to select the target cells and vectors.

作为心脏Fabry病基因治疗的基础研究，选择合适的靶细胞和载体至关重要。我们将评估小血管和毛细血管的内皮细胞和其他器官细胞作为靶细胞。在进行基因治疗的基础研究之前，我们必须明确Fabry病的表型和基因型，包括表现局限于心脏的非典型型Fabry病。我们将这种不典型的Fabry病命名为心脏Fabry病。我们检测到心脏法布里病的3%，男性患者的左心室肥大。他们没有血管角化瘤、多汗、肢端感觉异常或角膜混浊。经基因分析发现A20 P、E66 Q、M296 I等新突变。我们试图通过测定血浆α-半乳糖苷酶，在接受长期血液透析的男性患者中发现未确诊的法布里病患者。514例男性患者中有6例被发现患有法布里病，除1例外，他们没有血管角化瘤。通过基因分析，检测到A97 V和G373 D的新突变。在鹿儿岛县和宫崎县新发现的这些Fabry病的表型和基因型与经典Fabry病不同。我们认为，在进一步的研究中，应明确基因型和表型，以选择靶细胞和载体。

项目成果

Hiromitsu Tanaka: "Coxistence of gene mutation cacreig Fabry disease and DMD in a Japanese boy." Clinical Genetics. 49. 255-260 (1996)

Hiromitsu Tanaka：“基因突变 cacreig Fabry 病和 DMD 在日本男孩中共存。”

Toshihiro Takenaka: "Coexistence of gene mutatiens causing Fabry disease and DHD in a Japanese boy." Clinical Genetics. 49. 255-260 (1996)

Toshihiro Takenaka：“导致日本男孩法布里病和 DHD 的基因突变共存。”

Kohji Itoh at al.: "Immunofluerescence analysis of CTH accumulated in the hearts of variants hemizygotes and heterozygotes with Fabry diesase." American journal of Cardiology. 78. 116-117 (1996)

Kohji Itoh 等人：“法布里病变异半合子和杂合子心脏中积累的 CTH 的免疫荧光分析。”

Shoichiro Nakao: "Immunofluorescence analycis of efff accumlated in the heats of varient hemigggates and heterogyote with Fabry disease." American Journal of Coudislogy. 78. 116-117 (1996)

Shoichiro Nakao：“对患有法布里病的不同半球菌和异型菌的热量中积累的 efff 进行免疫荧光分析。”

Toshihiro Takenaka et al.: "Coexistence of gene mutations causing Fabry disease and DMD in a Japanese boy." Clinical Genetics. 49. 255-260 (1996)

Toshihiro Takenaka 等人：“导致日本男孩法布里病和 DMD 的基因突变共存。”