AstraZeneca explores new target for heart disease

LONDON—AstraZeneca has entered into a research collaboration with a small Swedish biotech firm to explore the potential for a new therapeutic target for heart disease. The company is partnering with Lipigon Pharmaceuticals to identify molecules that modulate lipoprotein lipase (LPL), an enzyme that plays a role in the metabolism of cholesterol. Lipigon, which specializes in LPL biology, has developed a screening platform to find molecules that affect the enzyme. Stefan Nilsson, CEO of Lipigon, believes that using the technology in collaboration with AstraZeneca could lead to the discovery of a drug that complements the use of statins in patients at high risk for heart disease.

“There have been many attempts to find compounds that are able to activate LPL, but it’s not easily done,” Nilsson tells DDNews. “What we’ve done is unique, and now by working with AstraZeneca we will be able to screen one-hundredfold more compounds than we have capacity for on our own.”

LPL, which is found mostly in fatty tissue and in muscles, plays a central role in breaking down fat into energy for immediate use by the body. When triglycerides accumulate in the blood as small lipid droplets after eating, they are too large to be absorbed by cells. LPL cleaves the fatty tails from the triglycerides to produce free fatty acids for use by the body. The surfaces of the fatty droplets combine to form the components of high-density lipoprotein (HDL), sometimes referred to as “good” cholesterol.

A drug that targets LPL has the potential to offer a new approach to the treatment of dyslipidemia and other conditions that mark high risk for cardiovascular and metabolic disorders. Statins are now widely used as a means of lowering “bad” low-density lipoprotein cholesterol levels in patients at high risk of heart disease. But pharmaceutical companies have had less success at developing drugs that address other imbalances in patients’ lipid profiles, such as elevated triglyceride levels and low HDL cholesterol levels.

Previous research has shown that people with low levels of LPL are more likely to have such imbalances. No drugs have been developed, however, that effectively and safely target the enzyme as a means of lowering triglyceride levels and raising levels of HDL cholesterol. Lipigon’s goal is to discover a prophylactic drug that accomplishes this.

“The ideal outcome would be a drug that can treat both low HDL and high triglycerides,” says Nilsson.

Lipigon has identified a number of compounds that it believes to hold the potential for such a drug and has examined these compounds in academic studies.

“We’ve shown these compounds to be quite powerful, and we got good data from in-vivo models,” says Nilsson. “This created interest in our company from pharmaceuticals and led to our partnership with AstraZeneca.”

Nilsson tells DDNews that a drug that targets LPL could be used in some patients to complement statins. “This would be a perfect complement for use with high-risk patients who are already on statin treatment,” he says. “This is important because statins in combination with other conventional treatments only prevent about 25 percent of heart attacks.”

The terms of the agreement call for the companies to use Lipigon’s screening platform to develop a high-throughput assay that identifies molecules that promote stabilization of LPL. “We’ve screened 17,500 compounds on our own, so the ultimate goal is to screen AstraZeneca’s compound library that includes a couple million,” says Nilsson. “That will give us a much greater chance of finding compounds that are even more efficient and more drugable than what we have right now.” Lipigon, which has already sent scientists to AstraZeneca to begin work, is receiving upfront payment in addition to milestone payments from the pharmaceutical company.

“This is an exciting opportunity where a small Swedish biotech company with an innovative approach complements AstraZeneca’s research in cardiovascular and metabolic diseases,” says Marcus Schindler, vice president of AstraZeneca’s Innovative Medicines unit. “Lipigon is internationally recognized for their scientific knowledge and technological know-how in a challenging area.”

Throughout its partnership with AstraZeneca, Lipigon will continue to explore the potential of compounds affecting LPL that it has already discovered on its own. “We want to work on the compounds we’ve found on our own so that we have all options available in terms of capital investment,” Nilsson tells DDNews.