Virginia Kimonis, chief of the division of genetics and metabolism at the University of California, Irvine, received an MDA grant totaling $372,000 to conduct experiments designed to uncover the underlying molecular cause of inclusion-body myopathy associated with Paget's disease of Bone and/or frontotemporal dementia (IBMPFD).
In 2004, Kimonis and colleagues published study results describing the rare disease IBMPFD and identifying the gene responsible for it — valosin-containing protein, or VCP. The group also created a mouse model that carries a flawed human VCP gene and exhibits symptoms similar to those in humans with IBMPFD, including decreased muscle strength and coordination, fatigue, enlarged vacuoles (bubblelike spaces) in the quadriceps muscles, swelling of cellular "energy factories" called mitochondria and abnormal protein clumps.
The Kimonis lab's new project includes the creation of a new mouse model aimed at providing proof of principle that amelioration of IBMPFD symptoms is possible. The team will evaluate functional and biochemical indicators to assess disease progression and effects in these mice. The group also will study whether physical exercise accelerates or decelerates the progression of muscle weakness in the mice, as a means of assessing what effects physical exercise may have on people with IBMPFD.
"Funding from MDA is critical for our laboratory to be able to continue this important work in understanding the key mechanisms related to this progressive and fatal muscle disease," Kimonis said. "Because of its similarities to other muscle disorders such as limb-girdle muscular dystrophy (LGMD), facioscapulohumeral muscular dystrophy (FSHD) and ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease), it's hoped that this research will advance a deeper understanding of mechanisms and potential treatments across a broad spectrum of neuromuscular diseases."
Funding for this MDA grant began August 1, 2010.