UA scientists find the missing link in muscle diseases

TUCSON, AZ (Tucson News Now) - There's a protein in your body you probably have never heard of, but, if you are an average adult, you have about one pound of it in your body.

The protein is called titin (pronounced: TYE-tin).

If something goes wrong with it, it can really cause serious health issues.

Now a discovery made at the University of Arizona is a first step toward finding a cure.

No one even knew titin existed until recently.

It's the largest protein in our bodies.  It's in our muscles--our hearts and our skeletal muscles.

Researchers had their suspicions about titin's role in muscle disease

Now, for the first time, a scientist has shown that genetic mutations in titin do cause disease.

That scientist is University of Arizona College of Medicine doctoral candidate Danielle Buck.

"Titin functions as a spring or something that's elastic, like a rubber band. And it's important in muscle to have this to prevent overstretching and breaking of your muscles and also to have them snap back into place after they're done," Buck says.

Buck has shown a direct link between titin and muscle disease.

She was under direction of her mentor, Dr. Henk Granzier, a UA Professor of Molecular and Cellular Medicine who also holds an endowed chair at the Sarver Heart Center.

Something goes wrong with titin. It mutates.

"When changes in titin take place, the muscle becomes more stiff and that leads to a cascade of changes that cause muscle disease to take place--muscle weakness, muscular atrophy, where the muscles are becoming smaller. All those things can happen," Buck says.

When titin mutates it can lead to muscle weakness, disability, even death

Scientists now know titin plays a role in enlarged hearts and in COPD, chronic obstructive pulmonary disease. COPD is a disease that makes it difficult to breathe. It gets worse over time.

Dr. Granzier says the end point for enlarged heart is a heart transplant or death.

Buck's discovery is the first critical step toward fixing the problem.

"Now we know that muscle is very stiff because of titin, we can create drugs to help reverse the stiffness that we're observing," Buck says.

Buck's discovery has enormous potential to eventually help millions of people.

Her proud mentor, Dr. Granzier, says one-third of patients with enlarged hearts have the disease because of a mutation in titin.

There is no cure--yet.

He calls the breakthrough discovery a "big deal."

"So you talk about millions of people worldwide and if you can figure out how to fix the titin-based problem, we would be able to cure these patients," Granzier says.

It's expected it will be several years before drugs and other therapies can be developed.

However, now scientists at the University of Arizona and around the world can build on what Buck and Granzier have done.

The findings are in the Journal of General Physiology.

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