PTC124 targets genetic disorders caused by nonsense mutations

Nonsense mutations promote premature translational termination and cause anywhere from 5-70% of the individual cases of most inherited diseases. Studies on nonsense-mediated cystic fibrosis have indicated that boosting specific protein synthesis from <1% to as little as 5% of normal levels may greatly reduce the severity or eliminate the principal manifestations of disease. To address the need for a drug capable of suppressing premature termination, we identified PTC124-a new chemical entity that selectively induces ribosomal readthrough of premature but not normal termination codons. PTC124 activity, optimized using nonsense-containing reporters, promoted dystrophin production in primary muscle cells from humans and mdx mice expressing dystrophin nonsense alleles, and rescued striated muscle function in mdx mice within 2-8 weeks of drug exposure. PTC124 was well tolerated in animals at plasma exposures substantially in excess of those required for nonsense suppression. The selectivity of PTC124 for premature termination codons, its well characterized activity profile, oral bioavailability and pharmacological properties indicate that this drug may have broad clinical potential for the treatment of a large group of genetic disorders with limited or no therapeutic options.     

Strong atom-field coupling for Bose-Einstein condensates in an optical cavity on a chip

An optical cavity enhances the interaction between atoms and light, and the rate of coherent atom-photon coupling can be made larger than all decoherence rates of the system. For single atoms, this 'strong coupling regime' of cavity quantum electrodynamics has been the subject of many experimental advances. Efforts have been made to control the coupling rate by trapping the atom and cooling it towards the motional ground state; the latter has been achieved in one dimension so far. For systems of many atoms, the three-dimensional ground state of motion is routinely achieved in atomic Bose-Einstein condensates (BECs). Although experiments combining BECs and optical cavities have been reported recently, coupling BECs to cavities that are in the strong-coupling regime for single atoms has remained an elusive goal. Here we report such an experiment, made possible by combining a fibre-based cavity with atom-chip technology. This enables single-atom cavity quantum electrodynamics experiments with a simplified set-up and realizes the situation of many atoms in a cavity, each of which is identically and strongly coupled to the cavity mode. Moreover, the BEC can be positioned deterministically anywhere within the cavity and localized entirely within a single antinode of the standing-wave cavity field; we demonstrate that this gives rise to a controlled, tunable coupling rate. We study the heating rate caused by a cavity transmission measurement as a function of the coupling rate and find no measurable heating for strongly coupled BECs. The spectrum of the coupled atoms-cavity system, which we map out over a wide range of atom numbers and cavity-atom detunings, shows vacuum Rabi splittings exceeding 20 gigahertz, as well as an unpredicted additional splitting, which we attribute to the atomic hyperfine structure. We anticipate that the system will be suitable as a light-matter quantum interface for quantum information.