GW1516 – How the “Spinach” went Bad

In 1992, GlaxoSmithKline along with Ligand Pharmaceuticals conducted a research for the treatment of Hyperlipidemia, which is a type of dyslipidemia – a condition where the lipid levels in the blood are abnormal. In the case of Hyperlipidemia, there is an abnormally increasing level of lipids, lipoproteins, or both. This led to the development of a substance that they called GW1516.

GW1516In the year 2000, phase I trials were conducted for the substance. In this phase, the product were tested on a group of human subjects. They, of course, were healthy. There were about twenty to a hundred people in the group. The phase aimed to find out at what dose, or range of doses, would the substance be safe to intake. This was done by giving a group of subjects a starting dosage and they remained be under observation until a number of half-lives (which is the time it takes for the substance to be half as pharmacologically active as compared to its initial state) have passed. The starting dosage will be based on the results of the previous phase, or phases that involved animal subjects. They took note of the amount of dosage that is harmful to the animals and set the starting dosage, for the human subjects, at an amount that is lower than the noted dosage. When no harmful effect was observed they gave a larger dosage to another batch of subjects. Since the same results were seen on the second group of subjects, a third batch was given an even larger amount of dosage. They wanted to reach a point where the dosage is observed to cause unwanted effects on the subjects and thus is no longer safe.

They moved on to phase II in 2002, which involved testing the substance on a larger number of human subjects, ranging from a hundred to three hundred subjects. The phase aimed to determine whether or not the substance will provide a therapuetic effect to the subjects and if it does, how much effect does it give. Toxic effects were also monitored. This phase is sometimes expressed as phase I/II. This is because the researchers carried out the same steps they did in phase I, but on a larger number of subjects, simultaneously.

A year after phase I began, the Proceeding of the National Academy of Sciences (or PNAS) published an issue about the discovery of GW1516. Then in 2003, by the results and developments made by GSK from phase I, Ligand Pharmaceuticals earned a one million dollar payment.

The third phase is supposed to determine whether the developed drug will perform its designed function on actual patients. However, phase III never materialized. In 2007, GSK stopped further developments on the substance GW1516. The reasons for abandoning the research on the drug were not disclosed.

In the same year that GSK abandoned their research, Cell, a scientific journal that published research papers, released studies by Ronald M. Evans (a biologist from Salk Institute for Biological Studies) that include the substance developed by GSK. Evans aimed to make drugs that would improve human endurance. Three years earlier Evans developed genetically engineered mice that , a nuclear hormone receptor, in their muscle cells. These[Symbol]produced PPAR mice were observed to have better physical endurance and improved even more after being given a dose of GW1516 that is greater than the dosage used by GSK. Doing the same experiment on lab rats showed improvements in metabolism and in the production of HDL or high-density lipoprotein, also known as good cholesterol that helps in preventing clogging of arteries. Fatty acids are also broken down quickly and easily. However, it was also discovered that the drug caused abnormal growths on the mucus membranes.

The World Anti-Doping Agency warned athletes of the dangers of this drug. GW1516 became one of the prohibited performance enhancing drug and was recently confirmed to have cancerous effects on numerous organs of the body.