18.02.2013 - European researchers have shown that depletion of immunosuppressant T lymphocytes boosts hypercholersterolemia and atherosclerosis in mice.
The findings lay the foundation for cell-based therapies against the fatal disease. Until now, several studies had supported the assumption that FoxP3-positive CD4+CD25+ T cells block the inflammatory processes that lead to the formation of atherosclerotic plaques in the blood vessels, which can cause cardiac infarction and stroke. But the team under Göran Hansson from Swedish Karolinska Institute was the first to demonstrate the effect in genetically engineered DEREG mice. Those mice express the diphteria toxin (DT) under control of a Treg-specific FoxP3 promotor.
Lethally irradiated, atherosclerosis-prone, low-density lipoprotein receptor–deficient (Ldlr–/–) mice received DEREG bone marrow and were injected with DT to eliminate FOXP3+ Tregs. The depletion caused a 2.1-fold increase in atherosclerosis without a concomitant increase in vascular inflammation. The mice also exhibited a 1.7-fold increase in plasma cholesterol and an atherogenic lipoprotein profile with increased levels of VLDL. Clearance of VLDL and chylomicron remnants was hampered, leading to accumulation of cholesterol-rich particles in the circulation. Functional and protein analyses complemented by gene expression array identified reduced protein expression of sortilin-1 in liver and increased plasma enzyme activity of lipoprotein lipase, hepatic lipase, and phospholipid transfer protein as mediators of the altered lipid phenotype. The results prove that FOXP3+ Tregs block atherosclerosis by modulating lipoprotein metabolism.
The findings are good news for drug developers, as Milan-based researchers have recently demonstrated that it is feasible to isolate functional Tregs and expand them in vitro. The patent has already been licenced to German T-cell Europe, which will use the technology for inducing immune tolerance after organ transplantation.
19.11.2014 It’s not every day that a company is pushed into the top ten of its sector, but that day has come for Actavis. Christmas came early for the new pharma giant after completing a US$66bn (€53bn) takeover battle for the Botox manufacturer Allergan.
18.11.2014 Merck KGaA and US rival Pfizer have signed a immuno-oncology alliance worth billions: Merck will share the development and commercialisation of its cancer antibody with its US partner – for €2.3bn.
14.11.2014 Cosily coinciding with World Diabetes Day on 14th November, French biopharma Les Laboratories Servier has struck a US$1bn deal with US pharma Intarcia Therapeutics for the exclusive rights to Intarcia’s unprecedented therapy for type 2 diabetes.
12.11.2014 Glitz and glamour are not words often used to describe science and mathematics. But once a year, celebrities from the science and showbiz world come together at the Breakthough Prizes, a glitzy television bash that honours scientists for their achievements. French life scientist Emmanuelle Charpentier was among this year’s winners.
04.11.2014 Galecto Biotech has entered an agreement with Bristol-Myers Squibb for the acquisition of the company and its lead drug, providing the Swedish company with the potential of reaching over US$400m.