Cardiovascular manifestations of Fabry disease and the novel therapeutic strategies.
Fabry disease is an inherited lysosomal storage disorder characterized by a pathological intracellular glycosphingolipid deposition. The disease is caused by a deficit in the lysosomal enzyme alpha-galatosidase A, the gene for which is located in the X chrosomal region Xq 22. Globotriaosylceramide (Gb3) accumulate progressively in multi-organ vulnerable cells throughout the body, including cardiovascular, renal, and cerebrovascular systems. The present manuscript is to review cardiovascular and renal manifestations of Fabry disease and the new diagnostic procedures for earlier detection and the therapeutic assessments of this disease. We are applying noninvasive cardiovascular and microcirculation analysis methods and novel cardiac biomarkers. Novel therapeutic strategies for this disease have been developing in recent years, which include the clinically introduced enzyme infusion replacement therapy and experimentally developing gene-transfer therapy. We have reported that AAV-mediated muscule-directed gene transfer is very effective for long-term systemic delivery of alpha-gal A (25% of normal mice enzyme activity), resulting in complete clearance of multi-organs Gb3 accumulation. Echocardiographic and immunohistochemical examination demonstrated structural improvement of cardiac hypertrophy. When and to whom the novel therapeutic strategies should be applied to obtain the maximum efficacy and safety remain to be established.
Seino
Yoshihiko
Y
The First Department of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan. y-seino@nms.ac.jp
Takahashi
Hiroshi
H
Fukumoto
Hiroko
H
Utsumi
Kouichi
K
Hirai
Yukihiko
Y
D000293:Adolescent; D000328:Adult; D000795:Fabry Disease / Q000150:complications* / Q000628:therapy*; D018014:Gene Transfer Techniques; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000209:etiology*; D007674:Kidney Diseases / Q000209:etiology*; D008875:Middle Aged; D000519:alpha-Galactosidase / Q000627:therapeutic use
D000519:alpha-Galactosidase