The good news widely reported this morning of positive results from a clinical drug trial at Boston Children's Hospital for the previously "untreatable" rapid aging disorder in children known as progeria has its scientific roots in basic biology discoveries made in recent years.
A paper published Monday in the Proceedings of the National Academy of Sciences (PNAS) reports that the use of farnesyl transferase inhibitors (FTI) significantly slows the progress of progeria, a rare and until now "untreatable" lethal genetic disorder. Also known as Hutchinson-Gilford Progeria Syndrome (HGPS), progeria has been described as out-of-control rapid aging in children. A ""normal"" baby born with HGPS will stop growing by 16-18 months and quickly develop signs of old age including hair loss, thin skin, osteoporosis and, most dangerously, progressive arteriosclerosis. By 10 years of age progeria children appear to be 80. The PNAS paper apparently shows a significant slowing of bone loss and blood vessel blockage.
This clinical trial grew out of the identification of the defective progeria gene, LMNA, in 2003 through the Human Genome Project and the laboratory of current NIH Director Francis Collins. But the link to defective proteins called lamins that make up the envelope surrounding the cell nucleus came about through "untargeted" basic cell biology research. Veteran lamin researchers remember having their grant applications dismissed by review panels as "boring" and irrelevant. But basic work by Robert Goldman of the Northwestern University School of Medicine and other nuclear lamin researchers around the world revealed that a greasy tag molecule called farnesyl accumulates on defective Lamin A proteins, eventually warping the structure of the entire nuclear envelope and disrupting the orderly production of genetic messages in the nucleus that direct normal growth.
The identification of the defective LMNA gene transformed progeria into a "laminopathy," a now growing class of diseases caused by problems with the once-irrelevant nuclear lamins. "Normal" aging is thought to involve many of the same processes as laminopathies and gives this new clinical trial implications beyond progeria. With the discovery of the lamin link, clinical researchers were suddenly looking for farnesyl transferase inhibitors (FTI) for progeria treatment. They zeroed in on Lonafarnib, an FTI drug developed by Merck that had been extensively tested and found safe for use in adults and children but ineffective against its brain cancer targets. In the two and a half year clinical trial, physicians at Boston Children's gave Lonafarnib to 26 children with progeria.
The American Society for Cell Biology has been reporting on progeria since 2006. In 2008, the ASCB Newsletter published a report on the proposed clinical drug trial. The ASCB has pulled together a file of these earlier reports for reporters and the general public interested in the deeper scientific background of progeria at: http://www.ascb.org/progeria-background.html
The PNAS paper was published online before print September 24, 2012, doi: 10.1073/pnas.1202529109 PNAS September 24, 2012 Gordon, Leslie B. et al, Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson–Gilford progeria syndrome
Reporters: For further information, contact ASCB Science Writer John Fleischman, firstname.lastname@example.org or 513-706-0212.
John Fleischman | EurekAlert!
Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg
Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
23.02.2018 | Life Sciences
23.02.2018 | Earth Sciences
23.02.2018 | Materials Sciences