by Sean Moore; posted 4 June 2009
It was during a seminar on the liver that Judy Anderson decided to see if nitric oxide (NO) played a role in muscle development and repair.
"I knew nothing of nitric oxide but I like going to seminars that have nothing to do with my work because I gain new perspectives. This seminar was about NO as a mechanism for something in liver, and I just began to wonder if it had anything to do with muscles. So I thought about it, read a few papers, and designed an experiment," the head of biological sciences said.
That seminar was 11 years ago, and now, in a recent paper published in Molecular Pharmaceutics, Anderson and her colleagues Frank Burczynski and Guqi Wang, showed that by attaching NO to an over-the-counter muscle relaxant, they activated a specific group of cells that stimulate skeletal muscle repair and growth.
Hugging every skeletal muscle cell or fiber is a group of satellite cells, stem cells that divide and then join the old fibers to make new muscle. Damaged muscles send a get-to-work signal to satellite cells. Anderson reported on this signaling in 2000; it involves NO and the discovery revealed a few new research paths.
One path revealed that muscular dystrophy does the opposite from what you might first think: It doesn't under stimulate satellite cells, it over stimulates and exhausts them. A drug, therefore, needs to turn the NO tap in the "off" direction. But sometimes, Anderson found, the tap needs to be turned towards "on," as in the case of atrophy.
Another path that her research may soon take, involves growing muscle for food in a variety of species.
"It might be that if you use more than one method to stimulate the growth of muscles in fish or chicken, you might get food more effectively because you are also using the muscle stem cells to add tissue rather than supplementing nutrition or hormones to force the animal to get bigger."
MyoNovin is the drug designed in her lab that can potentially do all this; for you chemists, it's a guaifenesin dinitrate compound. The muscle-relaxant used in this compound seems to act like a molecular taxi cab, giving NO a ride to the muscle.
In adult mice, an ointment formulation of MyoNovin on the skin increased satellite cell activation in the back and thigh compared to mice given a placebo, and the results were the same when an oral dose was given, so it's systemic. Anderson doesn't know if it travels anywhere else, but has so far found no side-effects of the drug.
The published studies were on healthy mice, and the lab is now examining MyoNovin effects on dystrophic mice and old mice to see the outcome and how it happens.
Nitric oxide itself is a formidable molecule, yet the gas is a key signaler and of vital importance to numerous body systems. Our muscles normally puff puff puff it out and these satellite cells get used to having regular NO puffs hit them.
"It's like rocking a baby," Anderson said. "You rock a baby gently and it falls asleep. Stop rocking it, or rock it too hard and it wakes up. It's the same with these satellite cells. That's what happens in muscular dystrophy: the cells wake up because the NO puffs are changed. So if we can start rocking it again at the right pace, it would be cool to see the cells respond normally to muscle damage. And if we can take old muscle in people like me, and wake it up by adding this drug, then we might be able to keep muscles strong in our aging population. Wouldn't that be neat!