http://www.mdlinx.com/internal-medicine/top-medical-news/article/2016/10/13/3
Helmholtz Zentrum München - German Research Center for Environmental Health News
Scientists
of Helmholtz Zentrum Munchen and Technical University of Munich have
developed a ‘smart’ drug that safely clears the liver of fat and
prevents blood vessels from clogging up. Similar to a trojan horse, the
drug enters the liver with a trick: It uses the pancreatic hormone
glucagon as vehicle to shuttle thyroid hormone T3 the live while keeping
it away from other organs, thereby improving cholesterol and lipid
metabolism while avoiding typical side effects of thyroid hormone.
An international team led by metabolism experts Matthias Tschop (Helmholtz Zentrum Munchen/Technical University of Munich), Richard diMarchi (Indiana University) and Timo Müller (Helmholtz Zentrum Munchen) report in the current issue of the journal Cell that liver–specific delivery of the thyroid hormone T3 using glucagon corrects obesity, glucose intolerance, fatty liver disease and atherosclerosis without causing adverse effects in other tissues.
“While the ability of T3 to lower cholesterol is known for centuries, deleterious effects, in particular on the skeleton and the cardiovascular system, do so far limit its medicinal utility”, says Brian Finan, the first author of the manuscript.
“Part of our trick is, that we use the pancreatic hormone glucagon as a vehicle to deliver thyroid hormone only into cells carrying a glucagon receptor”, says Christoffer Clemmensen, who led several of the key experiments. He explains: “Since there are lots of glucagon receptors in the liver, but almost none in heart or bone, our molecule concentrates thyroid hormone action to the liver while keeping it away from places where it would be harmful.” “The next task is to see whether this drug candidate will reach the same level of targeted tissue–selectivity in clinical studies”, says diMarchi. “If the molecule shows equal efficacy and safety in humans, then this particular ‘smart’ drug design may indeed offer perspectives for metabolic precision medicine”, summarizes Tschop.
An international team led by metabolism experts Matthias Tschop (Helmholtz Zentrum Munchen/Technical University of Munich), Richard diMarchi (Indiana University) and Timo Müller (Helmholtz Zentrum Munchen) report in the current issue of the journal Cell that liver–specific delivery of the thyroid hormone T3 using glucagon corrects obesity, glucose intolerance, fatty liver disease and atherosclerosis without causing adverse effects in other tissues.
“While the ability of T3 to lower cholesterol is known for centuries, deleterious effects, in particular on the skeleton and the cardiovascular system, do so far limit its medicinal utility”, says Brian Finan, the first author of the manuscript.
“Part of our trick is, that we use the pancreatic hormone glucagon as a vehicle to deliver thyroid hormone only into cells carrying a glucagon receptor”, says Christoffer Clemmensen, who led several of the key experiments. He explains: “Since there are lots of glucagon receptors in the liver, but almost none in heart or bone, our molecule concentrates thyroid hormone action to the liver while keeping it away from places where it would be harmful.” “The next task is to see whether this drug candidate will reach the same level of targeted tissue–selectivity in clinical studies”, says diMarchi. “If the molecule shows equal efficacy and safety in humans, then this particular ‘smart’ drug design may indeed offer perspectives for metabolic precision medicine”, summarizes Tschop.
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