New drug target may help reduce muscle damage caused by heart attacks

January 11th, 2010 - 12:58 pm ICT by ANI  

London, Jan 11 (ANI): An international team of researchers have discovered a potential therapeutic target that could help reduce muscle damage caused by heart attacks.

They have explained how a “chemical chaperone” does its job in the body.

The new class of drugs would work by restoring the activity of a mutated enzyme, rather than taking the more common approach of blocking the actions of a disease-related protein.

Lead researchers Dr Thomas Hurley, from Indiana University, and Dr Daria Mochly-Rosen, from Stanford University discovered a compound called Alda-1, which acts much like a shim to prop up a mutated form of a key enzyme, restoring the enzyme’s function.

The enzyme, called ALDH2, plays an important role in metabolizing alcohol and other toxins, including those created by a lack of oxygen in the wake of a heart attack.

It also is involved in the metabolism of nitroglycerin, which is used to prevent chest pain (angina) caused by restricted blood flow and oxygen to the heart.

Alda-1 activates the ALDH2 enzyme in a process that the researchers liken to a woodworking procedure in which Alda-1 attaches to the ALDH2 enzyme at a crucial spot and acts like a shim or wedge to prop it up.

“Because of the mutation in the gene, parts of the protein structure become loose and floppy. Alda-1 reactivates the enzyme by propping up those parts of the structure so they regain normal function,” Nature magazine quoted Hurley as saying.

He said determining how the Alda-1 compound works will enable the researchers to begin working on alternative compounds that hold more promise as potential drugs.

One primary improvement needed is the ability to give the drug orally, rather than by injection, he added.

The study appears in Nature Structural Biology. (ANI)

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