A Cedars-Sinai physician-scientist has been awarded a $3 million grant from the California Institute for Regenerative Medicine to study with new stem cell technology Charcot-Marie-Tooth disease, the most common inherited neurological disorder and which damages nerves that control muscles.
Robert H. Baloh, MD, PhD, director of the Neuromuscular Division of Cedars-Sinai's Department of Neurology and a member of the brain program at the Cedars-Sinai's Regenerative Medicine Institute, will lead the study of the disease, named for the three doctors who first described it in 1886. He and scientists in his Neurodegenerative Diseases Laboratory will employ induced pluripotent stem cells (iPSCs) created at the Regenerative Medicine Institute, which conducts stem cell research and produces stem cells for study at other institutions through its iPSC Core Facility.
Induced pluripotent stem cells have been stepped back, through genetic manipulations to a point where scientists can turn them into any of the body's mature cells, such as brain, blood and bone cells. This allows researchers to study a disease by reproducing it in a Petri dish; if they can learn about and correct its defective genetic makeup, they theoretically could cure the disease.
"Our studies funded by the CIRM grant will be 'preclinical' - laboratory research - to determine if we can generate personalized stem cell lines for individual patients," said Baloh, an expert in genetic defects and molecular mechanisms that cause neuromuscular and neurodegenerative diseases. "This would mean removing skin cells from a patient with this disease, converting them into induced pluripotent stem cells, genetically correcting them, and then transplanting them back into the patient to - we hope - restore normal nerve function."
More than 40 gene defects have been found to cause different forms of Charcot-Marie-Tooth disease, which most often damages the "insulation" around fibers in nerves that stimulate movement. Symptoms range from mild to severe and include weakness and numbness of the hands and lower legs. Patients often develop foot deformity and inability to lift their feet, which causes frequent tripping. They may have trouble using their hands for buttoning buttons and other common tasks. Many patients eventually require braces, wheelchairs and other supportive devices.
This study, which focuses on errors in a particular gene - PMP22 - is one of the first aimed at determining if stem cell therapies can be developed for patients with the disease. The PMP22 defect causes the single most common subtype of the disease, CMT type 1A, affecting about 11 people per 100,000 in the United States. It usually appears in childhood or early adulthood.
Baloh, who treats patients with this disease and other neurodegenerative and neurodevelopmental disorders, will lead a multidisciplinary Charcot-Marie-Tooth clinic, in coordination with Cedars-Sinai's Orthopaedic Center, Pediatrics Department and Medical Genetics Institute.
"We will strive to provide very efficient service, including diagnosis, treatment and genetic testing. Patients are often sent from doctor to doctor and physical therapist to physical therapist, spending a lot of time and resources trying to find the care they need or even get an accurate diagnosis," said Baloh, who has published groundbreaking discoveries in genetics and molecular biology of neuromuscular disorders.
"Several highly respected orthopedic surgeons are part of our multidisciplinary team because we are interested in determining if reconstructive surgeries for certain deformities can improve movement and quality of life for some patients with this disease. We also have pediatric neurologists, a medical geneticist and a certified genetic counselor," Baloh said. "One of our goals is to do the least expensive but accurate genetic testing, a daunting task for most neurologists in the community. While we cannot offer a cure for the disease at this time, we can help people understand it and learn about the risks of it occurring again in their family. Having an accurate diagnosis also will make it possible for patients to participate in clinical trials in the future, hopefully even those involving individualized stem cell lines such as the ones we are currently researching."
The California Institute for Regenerative Medicine was established in November 2004 with the passage of Proposition 71, the California Stem Cell Research and Cures Act, providing $3 billion in funding for stem cell research at universities and research institutions. CIRM previously awarded nine grants to Cedars-Sinai for a total of more than $30.3 million.
"We are very pleased to have received another CIRM grant at the Regenerative Medicine Institute to support the outstanding studies of Dr. Baloh," said Clive Svendsen, PhD, director of the Regenerative Medicine Institute.