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CENTER SCIENTISTS EYE A BASIC APPROACH TO
LET ALS PATIENTS BREATHE EASIER "If it works - and that's a considerable 'if, ' - such an approach could significantly lengthen patients' survival with the disease and improve their quality of life," says Jeffrey Rothstein, M.D., Ph.D., the Center's director. Recently, Packard Center scientists began several groundwork studies to learn exactly how ALS affects breathing. The researchers also hope to learn if the disease brings changes in body metabolism - something that also would have an impact on a person's need for oxygen and, hence, on breathing. "As far as we know, nobody's ever charted the respiratory changes that take place in a neurodegenerative disease such as ALS," says Center physiologist Clarke Tankersley, Ph.D. The researchers are studying animal models of ALS, mice with the same human gene that's disrupted in the small number of people with the familial form of the disease. "On a broad level," adds neurologist Jeremy Shefner, M.D., Ph.D., a Center advisor with the SUNY Upstate Medical University at Syracuse, "it's not clear in our mouse or rat models - or even, precisely, in patients - what brings about their demise. It could be weakened breathing, but malnutrition or even nutrition-related heart failure could be at fault." "But we'll need to know that, we'll need these basic studies to be able to see if gene therapy makes a difference," says Tankersley. "Also," Shefner adds, "the studies will enable us to prove that a new therapy targets what we think it's targeting." Both researchers say a better understanding of respiration in ALS may also suggest other ways to ease or extend patients' breathing ability. In his studies, Tankersley follows several different strains of the mouse models. He'll record breathing rate, for example, as well as the amount of air the animals inhale and their metabolic rate. By examining the model mice at 10, 14 and 17 weeks, he'll catch the period when their breathing efficiency changes. In both ALS patients and model mice, breathing strategies shift during the course of the disease. They move from using the diaphragm to employing intercostals or rib cage muscles. The latter technique, Tankersley says, uses more energy. Shefner's focus is on the breathing muscles themselves. He measures the diaphragm's ability to respond to nerve impulses, for example. He's already noted characteristic differences in muscle behavior in the course of the animal models' disease. In parallel with the breathing studies, other scientists with the team are working on the potential therapy end of things, readying approaches specifically targeted to respiratory muscles and the motor neurons that control them, sorting out ways to deliver therapy directly to the phrenic nerve that stimulates the diaphragm and trying to anticipate safety issues. "We hope that ultimately this will let us buy time for patients," says Rothstein. "It's not a cure," Tankersley explains, "but it's on the edge of preventing the problem that directly leads to death." Dr. Tankersley's laboratory is at the Bloomberg School of Public Health, Johns Hopkins University. |
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