There are no curative treatments for Tangier disease, but gene therapy for ABCA1 has been highlighted as a potential avenue for treating the disease, say the researchers of the paper.
Although gene therapy may have some potential in Tangier disease—a rare genetic disorder caused by a mutation of the ATP-binding cassette transporter A1—developing a treatment for the disease is complicated, say researchers of a new paper.
Tangier disease, which has been reported in approximately 150 people around the world, is characterized by extremely low levels or absence of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I. Estimates say that approximately 1 in 640,000 individuals has a loss-of-function variant in the ABCA1 gene, suggesting a significant amount of cases go unrecognized.
Currently, there are no curative treatments for the disease, but gene therapy for ABCA1 has been highlighted as a potential avenue for treating the disease, say the researchers.
Their findings appeared in a recent issue of Journal of Atherosclerosis and Thrombosis.
“There is the possibility that restoration of ABCA1 expression in the liver would raise serum HDL-C levels but this might not be enough to recover cellular cholesterol efflux and suppress extra lipid accumulation in cells in atherogenic lesions such as macrophages, smooth muscle cells, and endothelial cells,” commented the researchers. “It may not be easy to develop a fundamental therapy for Tangier disease.”
With a current lack of curative treatments, emphasis has been placed on identifying patients early and preventing atherosclerosis, as a heightened risk of atherosclerotic diseases has been implication in Tangier disease.
In one case study, i using intravascular ultrasound, a patient was found to have diffuse calcified coronary artery lesions, which the researchers say may have been affected by the HDL deficiency and glucose intolerance.
“It has been reported that 12 out of 35 patients (34.3%) in Japan and 34 out of 109 patients (31.2%) in other countries had some type of cardiovascular disease, suggesting accelerated atherogenicity in Tangier disease,” explained the researchers.
They recommended that patients be monitored for atherosclerotic lesions and managing atherosclerotic risk factors like hypertension and smoking. Monitoring includes regular testing through exercise electrocardiography, echocardiography, and CT coronary angiography.
According to the researchers, plasma low-density lipoprotein cholesterol levels are typically low in patients. If levels are not low, interventions such as statins should be used to lower them.
Koseki M, Yamashita S, Ogura M, et al. Current diagnosis and management of Tangier disease. J Atheroscler Thromb. Published online May 14, 2021. doi:10.5551/jat.RV17053