Researchers at the Technion-Israel Institute of Technology are proposing a revolutionary approach to prevent the common post-balloon angioplasty problem of restenosis (re-clogging of coronary arteries).
More than 1.2 million angioplasties were performed in the United States in 2003, according to the American Heart Association.Angioplasty is a minimally invasive procedure, during which a tiny deflated balloon is inserted into clogged arteries and inflated to open blockages. In many cases, a stent – originally mounted on the balloon – is then positioned inside the artery, against the arterial wall. Blockages – caused not by new fatty deposits, but by tissue growth from the walls of the blood vessel – re-occur in more than one-third of patients. Such growths, which doctors relate to as they would a cancerous growth, are most often treated with “anti-proliferative” medications that prevent uncontrolled tissue growth.
Because of the site-specific nature of these growths, the drugs to treat them must be delivered only to the affected tissue. Stent manufacturers currently include such drugs in their products for slow release over a six-month period (during which time the risk for restenosis is highest). Precise control of this release process can be tricky, however, and restenosis still occurs in many patients.
The new, patented technique – developed in the Technion Department of Biomedical Engineering by Professor Noah Lotan, Dr. Sarit Sivan and Professor Uri Dinnar – begins when the patient swallows a "pro-drug" compound. Inactive by itself, this compound can be taken for as long as necessary without side effects. It is activated only when it comes into contact with a specific enzyme attached to the stent by its manufacturer. In effect, the enzyme on the stent then becomes a "pharmaceutical factory" that manufactures an active anti-proliferative drug.
According to lead researcher Lotan, the pro-drug is an amino acid that is a safe and natural component of all proteins. When the risk of restenosis abates, patients could simply stop taking the pro-drug, and the stent would stop manufacturing the drug.
“This approach makes up a very general technological platform that can be applied for different medical problems,” said Lotan. “It has potential applications for every drug, known today or invented in the future, and could be useful for medications – including chemotherapy drugs – best administered to one very specific location in the body."
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