Asterion: tapping into the cells’ messaging system |
ONE OF THE big challenges for biomedical research is that fragile biological therapeutics are broken down rapidly in the body, requiring patients to take frequent doses. One promising way of countering this might be to mimic, biochemically, the body's own mechanism for protecting hormones in circulation, which is to bind them with particular proteins.
Researchers at the University of Sheffield, led by Professor Pete Artymiuk, have unravelled the basic structural biology of the hormone-protein pairing. The breakthrough creates possibilities for a wide range of tailor-made therapeutic proteins to treat conditions such as cancer, diabetes and infertility, with significant benefits for patients in terms of dosage frequency.
Artymiuk and his colleagues, Professor Richard Ross and Professor John Sayers, have now commercialised their work in a Sheffield University spinout, Asterion Ltd. The company is developing novel therapeutics for a range of conditions caused by faults in cell signalling – such as the growth disorder acromegaly, and neutropenia, which affects white blood cell production. By fusing novel proteins, derived from recombinant DNA technology, with synthetic hormones, Asterion hopes to develop drugs which will intervene to correct cellular signalling processes.
The catalyst for the new approach was a rare disease known as Laron's syndrome. In this condition, a patient’s growth is restricted because their cells cannot respond properly to circulating growth hormone. This insensitivity to growth hormone, the researchers found, was due to the hormone receptor molecule lacking a key protein. By fusing, in a series of experiments, different elements of hormone and receptor, the team were able to correct cellular function in Laron's disease and its 'opposite' condition, acromegaly – which results in excessive growth.
Asterion's commercialisation is built on years of fundamental research at Sheffield, funded by The Biotechnology and Biological Sciences Research Council (BBSRC). Prof. Ross, Asterion’s Chief Scientific Officer, explains: "The basic structural biology work we have done in the past means that we can see the interaction between the hormone and the binding protein in exquisite detail. Our understanding of this structural information means that we can rationally design drugs that consist of this pairing of hormone and binding protein that still allows them to activate the cell surface receptor. In this situation, the hormone portion of the drug is better protected in the circulation from degradation and so it has a much longer effective life in the body."
Asterion's system of drug design has been developed into a patented and versatile therapeutic platform technology called ProFuseTM. Using this technology it will be possible to make other useful pairings between therapeutic hormones and protective receptor domains (the binding proteins) to tackle a wide range of cellular disorders. For patients, there is the welcome possibility of monthly injections rather than the daily treatments needed for most of the drugs currently in use.
Asterion Ltd is supported by the University of Sheffield, Biofusion and White Rose Seedcorn Fund. |
