A small short-term trial using bacterial synthesized human Apo-A1 Milano HDL in people with unstable angina produced a fairly dramatic reduction in measured coronary plaque volume in only six weeks vs. the usual increase in plaque volume in those randomized to placebo. The trial was published in JAMA in early 2006. Ongoing work starting in the 1990s may lead to human clinical trials—probably by about 2008. These may use synthesized Apo-A1 Milano HDL directly, or they may use gene-transfer methods to pass the ability to synthesize the Apo-A1 Milano HDLipoprotein.Methods to increase HDL particle concentrations, which in some animal studies largely reverses and removes atheromas, are being developed and researched. However, increasing HDL by any means is not necessarily helpful. For example, the drug torcetrapib is the most effective agent currently known for raising HDL (by up to 60%). However, in clinical trials, it also raised deaths by 60%. All studies regarding this drug were halted in December 2006.The actions of macrophages drive atherosclerotic plaque progression. Immunomodulation of atherosclerosis is the term for techniques that modulate immune system function to suppress this macrophage action.Involvement of lipid peroxidation chain reaction in atherogenesis triggered research on the protective role of the heavy isotope (deuterated) polyunsaturated fatty acids (D-PUFAs) that are less prone to oxidation than ordinary PUFAs (H-PUFAs). PUFAs are essential nutrients – they are involved in metabolism in that very form as they are consumed with food.
Ixabepilone (INN; also known as azaepothilone B, codenamed BMS-247550) is a pharmaceutical drug developed by Bristol-Myers Squibb as a chemotherapeutic medication for cancer. History
Ixabepilone is a semi-synthetic analog of epothilone B, a natural chemical compound produced by Sorangium cellulosum. Epothilone B itself could not be developed as a pharmaceutical drug because of poor metabolic stability and pharmacokinetics. Ixabepilone was designed through medicinal chemistry to improve upon these properties. Pharmacology
Much like Taxol, Ixabepilone acts to stabilize microtubules. It is highly potent, capable of damaging cancer cells in very low concentrations, and retains activity in cases where tumor cells are insensitive to taxane type drugs. Approval
On October 16, 2007, the U.S. Food and Drug Administration approved ixabepilone for the treatment of aggressive metastatic or locally advanced breast cancer no longer responding to currently available chemotherapies. In November 2008, the EMEA has refused a marketing authorisation for Ixabepilone.Ixabepilone is administered through injection, and is marketed under the trade name Ixempra. Clinical uses
Ixabepilone, in combination with capecitabine, has demonstrated effectiveness in the treatment of metastatic or locally advanced breast cancer in patients after failure of an anthracycline and a taxane.It has been investigated for use in treatment of non-Hodgkins lymphoma. In pancreatic cancer phase two trial it showed some promising results (used alone). Combination therapy trials are ongoing. References
External links
Ixempra product website
Ixempra prescribing information