Major expansion of BSCI Research
At the end of 2006 our BSCI technology platform was sub-licensed from the french pharmaceutical company Ipsen to a newly formed Cambridge biotechnology company, Funxional Therapeutics (FXT). After a successful year working with FXT, they have today announced the expansion of their collaboration with Cambridge University to further support our BSCI research programme.
The company has agreed to spend a total of £290,000 over the next year on research into the mechanism of action of the BSCI class of anti-inflammatory drugs This represents almost a doubling of the support provided, and will allow a substantial increase in the size of our research effort in this area.
FXT has now selected its lead compound for clinical development, and is currently completing regulatory toxicology and other preclinical studies to support the filing of an IND by the end of 2008. Subject to successful completion of these safety studies, phase I clinical trials in man are expected to begin in the first quarter of 2009. Our work during 2007 has continued to support the development of these compounds in respiratory indications, and FXT expects to develop the lead compound for the prevention of allergic rhinitis, asthma or COPD. However, the anti-inflammatory efficacy of BSCIs, which resemble corticosteroids without the side-effects, mean that agents of this class will likely be developed for a range of other indications in addition, and preclinical model studies in surgical adhesions, diabetic nephropathy and rheumatoid arthritis are also underway.
Broad-spectrum chemokine inhibitors (BSCIs) are a fascinating new class of compounds which block the migration of leukocytes in response to a wide range of pro-migratory cues from different chemokines, but leave migration in response to other signals (such as C5a or TGF-beta) untouched. Some cells of the immune system (such as macrophages) are exquisitely sensitive to BSCIs, while others (such as B cells) seem much less affected. The reason for this difference has recently been traced to a single G-protein coupled receptor in the cell surface, which is the target for BSCI binding.
The new funding is to continue our work in this area, to confirm the identity of this target receptor, and to better understand why engaging this particular receptor leads to the wide array of beneficial effects on the immune system which have previously been reported. In particular, we aim to understand just how BSCIs are able to "re-balance" the T-helper cell axis during inflammation. Many inflammatory diseases are characterised by a persistent imbalance in the T-helper cell cytokine profile (with either Th1 or Th2 cells dominating). Treatment with BSCIs (even for just a few days) normalises that balance irrespective of whether the original bias was in favour of Th1 or of Th2. To date, BSCIs are the only compounds yet described with such a "re-balancing" effect.
The funding will also support further collaboration with the Chemistry Department, and in particular the laboratory of Dr David Spring, synthesising and characterising new BSCIs, as well as with the laboratory of Dr David Fox (University of Warwick) who invented the acylaminolactams currently in clinical development.
Related links
Much more information about our BSCI rseaerch program, and in particular the use of BSCIs as anti-inflammatory drugs, can be found elsewhere on this website.
The Chemotide family of BSCIs, invented in the IRTL, Cambridge University, are currently licensed to the Cambridge-based biotechnology company Funxional Therapeutics.
Free full text access to a publication in Retrovirology, desxcribing an unexpected effect of BSCIs on HIV replication, can be found here.
In 2005, we published a manuscript describing the nanomolar potency aminocaprolactam BSCIs, which might be the most useful for development a potential new HIV therapeutics, in the Journal of Medicinal Chemistry.
Dr David Spring in the Department of Chemistry also has a group website.