2009/07/23

A North American bio-company to market a CIC bioGUNE product for developing anti-cancer drugs

The CIC bioGUNE Biosciences Research Centre has reached an agreement with the North American biotechnology firm LifeSensors to license them to market a product (TUBEs) which will enable the development of drugs for pathologies involving protein metabolism problems, such as cancer and neurodegenerative diseases.

The product, called TUBEs (Tandem-repeated Ubiquitin Binding Entities), was entirely developed in the laboratory of Dr Manuel S. Rodríguez, from the Proteomic Unit of CIC bioGUNE, and consists of an innovative, first of its kind tool which captures and "freezes" ubiquitinated proteins (proteins whose principal function is to mark other proteins for destruction) in order to enable the identification of target proteins of therapeutic interest.
In short, what Dr Rodríguez has developed is a kind of "molecular trap" to enable the proteins involved in a pathology to be captured and purified, so that we can learn more about their functioning in key cellular processes. "It is a tool which serves not only to explore cellular processes, but also to develop drugs which have beneficial effects on pathologies such as certain immune and inflammatory diseases, neurodegenerative disorders and different types of cancer," states Dr Manuel Rodríguez.
The research project is based on a protein degradation pathway known as the ubiquitin-proteasome system, which was discovered by the Israeli scientist Aaron Ciechanover, who won a Nobel Prize in Chemistry in 2004 and who visited CIC bioGUNE in 2006. As Manuel Rodríguez explains, "this pathway is involved in many different processes vital to cell functioning," which are extremely complex and difficult to understand. "What we don't know is how these processes are regulated, because they are highly dynamic and reversible. We have invented this ubiquitin "trap" to learn more about how these processes are regulated in both a normal and pathologic state and to identify targets of therapeutic interest," continues Dr Rodríguez.
Thanks to this new tool, the protein degradation process can be characterised in more detail and new inhibitors such as Velcade, also known as Bortezomib (currently being used to treat certain types of cancer) can be developed.
Ubiquitin is a small protein which is naturally expressed in eukaryotic cells. Its principal function is to tag other proteins for degradation. This process is known as proteolysis. Various ubiquitin molecules bond to the protein to be eliminated and the protein then moves towards the proteasome, the structure in which proteolysis takes place. Ubiquitin can even tag or label proteins of the cell membrane, such as receptors for example, to eliminate them from the membrane.
"Until now there was no tool that enabled you to capture or 'freeze' the ubiquitinated protein at any given moment and identify the associated proteins, i.e. those that regulate transcription, degradation, cell cycle and the scheduled cell death, etc. The tools used were either antibodies or a chemical method based on nickel columns. In both cases, it was impossible to maintain interactions. These 'traps' enable us to take a long sequence of photographs in order to obtain a kind of molecular x-ray of the whole process. This enables us to identify the associations present at each moment."
When the ubiquitin-proteasome system (or UPS) was demonstrated to be a valid target for drug development, a frantic scientific race began to identify pharmacological targets from among the numerous regulatory steps of the UPS. Increasing our knowledge in this area has become a vital necessity for identifying critical regulators involved in this process.

LifeSensors

The biotechnology company LifeSensors specialises in the discovery, development, manufacture and marketing of technologies within the field of UPS proteins. Its customers are the pharmaceutical industry and other biotechnology companies, as well as institutes and basic research centres. LifeSensors emerged from and collaborates with the prestigious research centre Progenra, a world leader in research into ubiquitin routes and the discovery of new drugs.

CIC bioGUNE

Since its inauguration in January 2005, CIC bioGUNE has set itself the objective of becoming a key player on the international biomedicine research scene. To this end, it has attracted a wide range of talented researchers from all over the world to its headquarters in Bizkaia, and has established collaboration agreements with other leading scientific institutions. The centre focuses on diseases which have a major social impact, such as cancer, its prevention, diagnosis and the identification of drugs for customised therapies.
The work carried out by CIC bioGUNE forms part of the BioBasque strategy established by the Basque Government with the aim of turning the Basque Country into a leading region within the field of biosciences. The Basque centre has, in this sense, established close collaborative ties between the academic and business worlds, leading to the setting up of a cluster of firms with excellent perspectives in hepatology, cancer, neurosciences and bioinformatics.
Directed by Professor José M Mato, CIC bioGUNE has, to date, established technology platforms in Genotyping, Proteomics, Metabolomics, Gene Silencing and Structural Biology, all fully equipped with the very latest technology.