One of the fastest translations of a basic research discovery into a promising clinical trial for an "untreatable" and fatal disorder will be discussed publicly for the first time by the key players in this remarkable research story, on Sunday, Dec. 14, at the American Society for Cell Biology (ASCB)'s annual meeting in San Francisco.
The disease is Progeria, or Hutchinson-Gilford Progeria Syndrome (HGPS), a rare, accelerated aging disease that afflicts children.
The discovery of the gene responsible for the disease five years ago led scientists to the experimental drug that is now being evaluated in 28 children with this "premature aging" disease.
Speaking at the special ASCB session will be the physician heading the clinical trial, the gene-hunter whose research team pinpointed the DNA mutation, and the cell biologist who conducted the basic research on the protein structures in the cell nucleus that were subsequently found to be abnormal in HGPS.
Also on the panel will be the medical director of the Progeria Research Foundation who is both a scientist and the mother of a child with HGPS.
In addition to describing this bench-to-bedside story, the ASCB special symposium will spotlight new research suggesting that the basic cellular mechanism defective in children with HGPS may be at work in "normal" aging disorders, particularly in cardiovascular disease.
HGPS is estimated to affect about one child in 4 million. At birth, children with the disease appear normal. However, their growth soon slows, and children with HGPS begin to show signs of accelerated aging, such as hair loss, wrinkled skin, and loss of body fat. A 10-year-old child with HGPS typically looks like an 80-year-old adult.
HGPS' lethal damage occurs within the major blood vessels. The children develop premature cardiovascular disease, which typically leads to death from heart attack or stroke at about the age of 13. There currently are no treatments for the disease.
Speaking at the symposium will be:
o Robert D. Goldman, Ph.D., a pioneer in basic research relevant to understanding how the HGPS gene mutation disrupts human body cells. The head of cell biology at Northwestern University Medical School in Chicago (and ASCB's current president), Dr. Goldman has long studied the normal structure and function of a major component of the scaffold-like network of proteins just inside the membrane that surrounds and protects the cell's nucleus. His research team identified the component, called nuclear lamins, as the culprit in HGPS;
o Gene-hunter Francis Collins, M.D., Ph.D., the former National Human Genome Research Institute (NHGRI) director who headed the research team that pinpointed HGPS' genetic mutation in 2003. Just two years later, NHGRI scientists identified the class of experimental cancer drugs, called farnesyl transferase inhibitors (FTIs), that can prevent the cell damage caused by the gene mutation and thus might provide an effective therapy against the disease;
o Harvard Assistant Professor Mark Kieran, M.D., Ph.D., the principal investigator of the Boston Children's Hospital phase 2 clinical trial that is evaluating a FTI drug in children with HGPS. He is director of Dana-Farber Cancer Institute's Pediatric Medical Neuro-Oncology;
o Leslie Gordon, M.D., Ph.D., parent of a child with the disease and medical director of the Progeria Research Foundation, which is funding the clinical trial and which has been the "mover and shaker" in accelerating research on the disease.
The symposium will be held at 12:15 ��:45 pm, Sunday, Dec. 14, at San Francisco's Moscone Center.
The 28 children enrolled in the clinical trial range in age from 3 to 15 years old and come from 16 countries. The two and one-half year phase 2 clinical trial, which began in 2007, is evaluating the FTI drug lonafarnib. In clinical studies in people with myeloid leukemia, neurofibromatosis and other conditions, FTIs' side effects were minimal.
The 2003 discovery of the HGPS gene, named lamin A (LMNA), laid the groundwork for the clinical trial. Indeed, in 2003, Dr. Collins was quoted as saying, "This genetic discovery represents the first piece in solving the tragic puzzle of Progeria. Without such information, we in the medical community were at loss about where to focus our efforts to help these children and their families. Now, we finally know where to begin."