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Tenecteplase

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Subject: Tissue plasminogen activator, ATC code B01
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Tenecteplase

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Tenecteplase (TNK) is an enzyme used as a thrombolytic drug.

Tenecteplase is a tissue plasminogen activator (tPA) produced by recombinant DNA technology using an established mammalian cell line (Chinese hamster ovary cells). Tenecteplase is a 527 amino acid glycoprotein developed by introducing the following modifications to the complementary DNA (cDNA) for natural human tPA: a substitution of threonine 103 with asparagine, and a substitution of asparagine 117 with glutamine, both within the kringle 1 domain, and a tetra-alanine substitution at amino acids 296–299 in the protease domain.

Tenecteplase is a recombinant fibrin-specific plasminogen activator that is derived from native t-PA by modifications at three sites of the protein structure. It binds to the fibrin component of the thrombus (blood clot) and selectively converts thrombus-bound plasminogen to plasmin, which degrades the fibrin matrix of the thrombus. Tenecteplase has a higher fibrin specificity and greater resistance to inactivation by its endogenous inhibitor (PAI-1) compared to native t-PA.

Research

Researchers at Newcastle University in Australia say they have had a significant breakthrough in treating stroke patients using the commonly used drug, with some people showing "Lazarus-like" recoveries. The findings published in the New England Medical Journal show, in some cases, stroke victims using Tenecteplase making almost miraculous recoveries within days.

One of the study's authors, Dr Neil Spratt from John Hunter Hospital, says the drug is commonly used for heart treatment, but preliminary results show it also helps stroke victims. The three-year study was trialled on 75 patients. Dr Spratt says there were a number of patients who had "Lazarus-like responses" to the new drug, with some patients on their feet within an hour of taking it. "People who came in really completely paralysed - one of my patients, a young woman, came in completely paralysed down one side of her body and unable to speak - and an hour after receiving the drug she essentially has normal strength and normal speech, and she's gone on to do fantastically well," he said.

But Dr Spratt says more tests will need to be run before the drug is widely used in stroke patients, and adds, "Even if the results [of a further trial] are only half as good as those from our smaller trial, I think it's likely to become licensed and become the new standard of care for stroke worldwide,"

External links

  • uspdi-500145
  • http://www.abc.net.au/news/2012-03-22/stroke-study-makes-treatment-breakthrough/3905512
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