Of Mice and Men

At the Khurana Lab, a cure for muscular dystrophy might be just an RNA splice away.

by Mary Armstrong

Michael T. Regan MUSCLEBOUND: Catherine Moorwood's experiments focus on utrophin, a protein that can be stimulated in muscular dystrophy patients to take the place of their damaged dystrophin.

Out the window of the sixth floor of the Richards Building, you've got an aerial view of UPenn's quad. Inside, there's a poster taped to the wall at eye level — a mouse of distinctive piebald coloring, posed upon the hip pocket of some upscale denims. It's an ad for a company that sells specially bred lab mice to scientists. The slogan? "Designer Genes."

This is the Khurana Lab, part of the Pennsylvania Muscle Institute, and the layout of the place can leave a first-time guest feeling a bit like a mouse in a maze. After much turning of corners and threading through busy corridors and passages, I come to Catherine Moorwood, recently minted Oxford Ph.D. and West Philly resident of just under a year.

Moorwood comes from Woking, Surrey, south of London in the U.K. There, she grew up watching her brother, Michael, struggle with muscular dystrophy (MD). That's what spurred her interest in biochemistry and her eventual doctorate. When lab founder Tejvir S. Khurana — previously of Harvard and the University of Copenhagen — was looking for new scientists, he contacted a former colleague now at Oxford, under whom Moorwood had been studying. Since last February Moorwood has been devoting herself to finding interventions for MD at Penn.

A typical day for Moorwood sounds like a dream for the curious. "I make a list of experiments I want to work on. I usually work on three simultaneously."

Moorwood is particularly focused on utrophin, a protein that can be stimulated in MD patients to work in the place of damaged dystrophin.

Micro RNAs, a tiny piece of the genetic puzzle, are one of Moorwood's experiments. Working below the DNA level, she is attempting to restart the gene to produce utrophin. The idea is to splice RNA to the side that turns off utrophin production and, in theory, let the cell return to making this substance which slows the muscle decline in MD patients.

For a change of pace, Moorwood can switch to testing pre-existing molecules on a cell-based assay. "The cells are immortal," she says. Responding to quizzical looks, she explains that originally they were probably some type of cancer — abnormal cells that go on reproducing forever. That makes the cell an ideal standard, each one identical and ideal for experimenting on.

This study works with molecules of drugs already on the market, hoping to identify some that may be as-yet-unidentified utrophin stimulants. To make their effectiveness obvious, the cells include the chemical that makes light in fireflies. When the drug molecule attaches, the first sign of a potentially useful drug, the firefly light glows.

An insistently ringing phone breaks Moorwood's tale. This time it's Gabriel Willmann, a lab partner recently relocated to Germany. Much as she'd like to hear how his work with opthalmology is coming along, she passes him on to Khurana.

Khurana founded the lab in 1997 at the Department of Clinical Biochemistry and Experimental Medicine at Glostrup Hospital, Denmark. He moved the lab to Penn in 2000.

"We have people working on hypoxia — low levels of oxygen," explains Moorwood, returning to present company. Some believe MD patients may be hypoxic. Lab partners Khurana and Willmann have climbed Mount Everest and Mount Denali to test the effects of hypoxia on a number of lab subjects: flies, mice and, unavoidably, themselves.

After Khurana gets off the phone, he stops by and takes up describing the lab's work and leads me deeper through the maze of labs. We see cages of mice being tested in lab-induced hypoxia, complete with what look like the world's tiniest breathalyzers. OK, the mouse isn't actually persuaded to blow into the thing, but the outcome is similar: an analysis of breath chemistry.

In his office Khurana describes some of the rigors of those trips. "High altitudes induce a 20 percent drop in muscle mass within 14 days. Blood thickens at high altitudes, so Gabi [Willmann] and I were popping aspirins. We also climbed with oxygen masks." A physician as well as a research scientist, Khurana developed newfound sympathy for those who swear it is impossible to sleep with the contraptions. But after not too long, waking to shortness of breath makes a climber put it right back on. He also smiles recalling climbing Denali with lab animals tucked inside his jacket to keep them viable. An early love of mountain climbing has inspired Khurana's science since his youth in India and on through a year in Kenya.

We continue the tour upstairs, and come across some custom-built testing apparatus specifically designed for compactness and portability. Khurana tells of stuffing that whole section of the lab into the back of his car for a recent trip to Rhode Island. Sometimes you have to bring the lab to the mice.

(m_armstrong@citypaper.net)