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CHOP Researcher to Launch Company to Sell Cellular Assays That Probe Cholesterol Flux

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A lab at Children’s Hospital of Philadelphia plans to start a company that will develop and license cell-based assays designed to determine the flux of cholesterol molecules between cells and serum lipoproteins such as high-density lipoprotein, or HDL.
 
Lipid Sciences, a drug-development company based in Pleasanton, Calif., last month announced that it has licensed the technology from CHOP to help it validate investigational treatments for cardiovascular disease as it readies them for regulatory approval.
 
The technology comprises a pair of cell-based assays for cholesterol efflux: The first assay measures scavenger receptor class B type I-mediated cholesterol efflux, while the second measures ATP binding cassette protein 1-mediated cholesterol efflux.
 
According to inventor George Rothblat, a professor of pediatrics at the Joseph Stokes, Jr., Research Institute at CHOP, the assays are designed to look at serum HDL taken from patients given an investigational drug and from controls to see which sample stimulates greater cholesterol efflux and by what mechanism.
 
The technology is described in US Patent No. 7,029,863, entitled “Cell culture system for determining the cholesterol efflux potential for serum.” (See CBA News, 6/16/06)
 
The technology is spun off of Rothblat’s previous work on reverse cholesterol transport, a process in which high-density lipoproteins target, bind, and remove coronary artery plaques. 
 
Rothblat this week told CBA News that he plans to outlicense the technology through a start-up company called Vascular Strategies. He said his lab is developing other assays that look at HDL and HDL function in human serum.
 
Launching the company will be Rothblat, Steven Adelman, president of Vascular Strategies, and Dan Rader, a professor of medicine, pharmacology, and laboratory medicine at the University of Pennsylvania, according to Adelman.
 
“The three of us decided that reverse cholesterol transport is an important area that is not being investigated thoroughly enough,” Adelman said.
 
The focus of the company is investigating the function of HDL, also known as “good cholesterol,” said Adelman. He said that Vascular Strategies and its customers will try to learn, for example, what does HDL isolated from a specific patient do in the body, can the HDL accept cholesterol from the vascular wall — which is known to help prevent many kinds of cardiovascular diseases — and does the HDL return cholesterol to the liver for excretion?
 
The start-up also intends to look at the steps involved in removing cholesterol from the vascular wall, Adelman said. “We have a number of assays available, and we are developing other assays to characterize the functionality of reverse cholesterol transport.” 
 
Rothblat’s assay technology has been licensed to Lipid Sciences, a drug-development company based in Pleasanton, Calif., to help it validate investigational treatments for cardiovascular disease as it readies them for regulatory approval.
 

“We decided that reverse cholesterol transport is an important area that is not being investigated thoroughly enough,”

The intent is to make Vascular Strategies the main licensee of these assays, said Adelman. He explained that the company will offer its services to other companies for use in their drug-development and -discovery process.
 
Adelman said the company has a number of prospective customers lined up, but declined to elaborate.
 
Vascular Strategies also wants to develop its own compounds, said Adelman, who said he has 20 years of drug-development experience, among them as an investigator with Wyeth, where he said he moved “at least 10 compounds” into clinical trials.
 
According to Adelman, the next step is to run the assays and begin testing compounds for companies other than Lipid Sciences. In addition, the company is looking to identify and characterize compounds for atherosclerosis-reversal indications.
 
“We have had some discussions regarding testing clinical samples in addition to preclinical samples,” said Adelman. “Plasma samples will be run through our assays. If someone has been treated with a compound that modifies HDL, we will see if the HDL is a functional HDL or if it is just getting arrested in the process, so to speak.”
 
Adelman said Vascular Strategies also plans to submit proposals to small business innovation research programs to fund in-house compound development.  
 
Rothblat’s technology is applicable to areas other than atherosclerosis, Adelman said, including diabetes, metabolic syndromes, or any area where there is a defect in lipid metabolism.  

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