Dundee Drug Discovery Unit
A bloodstream form of a trypanosome (yellow) among host red blood cells. Credit: Gull Lab, Sir William Dunn School of Pathology, Wellcome Images
The Dundee Drug Discovery Unit was founded in 2006 at the University of Dundee. Its aim is to create new drugs for neglected diseases, in particular human African trypanosomiasis (sleeping sickness), which affects the very poorest in sub-Saharan Africa, and also to translate basic research into therapeutics in many other areas, including cancer and allergy.
Background
While there have been major strides in recent years in tackling the neglected diseases, much of the focus has been on the 'big three': malaria, tuberculosis and HIV. Other conditions, such as African sleeping sickness, leishmaniasis and Chagas' disease (collectively known as haemoflagellate diseases), have received little attention yet present serious public health problems in many of the poorest regions of the world and remain difficult to treat.
The Wellcome Trust Biocentre at the University of Dundee has a concentration of some of the top researchers in haemoflagellate parasite biology. Recently, the University made a commitment to establish a major new initiative in medicinal chemistry and an £18 million facility has been co-located on the Biocentre site. With a Strategic Award from the Trust, a group led by Professors Mike Ferguson and Alan Fairlamb has instigated a drug discovery effort focused on these neglected diseases.
The £8.1m award from the Trust has enabled the University to appoint key personnel from the biotechnology sector and industry to lead the creation of a drug screening and medicinal chemistry operation of comparable capability to that found in a small company. For example, Paul Wyatt, Head of Drug Discovery, was recruited from Astex Technologies, while Julie Frearson (who heads the screening facility) was attracted from Biofocus Ltd. A compound library has now been amassed and the robotics for screening installed; the first assays were run during 2006.
Making a difference
Unusually for an academic group, the Dundee operation is attempting to establish drug discovery facilities and a management structure designed to advance the research and development in small-molecule therapeutics from a validated drug target to an optimised lead compound/preclinical candidate. The initial portfolio of projects comprises more than a dozen putative drug targets. A subset of these is given priority at any one time as in a company setting; these will proceed or be replaced according to the rate of progress against predetermined criteria linked to the requirements specified by a target product profile.
By 2007, the drug discovery facility had built up core resources for small-molecule robotic screening, assay development, virtual screening and medicinal chemistry, with recruits largely from industry. An important addition in 2008 was the acquisition of pharmacology and toxicology expertise with the ability to run drug metabolism and pharmacokinetic (DMPK) assays in-house. The facility integrates rational drug design with the Wellcome Trust Biocentre's strength in structural biology, which is supplemented by a computational chemistry resource.
In total there are personnel with more than 170 years of industrial drug discovery experience working at the facility. The resource has attracted an industrial collaborator and, during 2007, international collaborations with both the Swiss Tropical Institute and the Max Planck Institute of Molecular Cell Biology and Genetics were initiated. The facility has a leadership position with external international consortia that share a common interest in drug discovery outside of industry.
The disease focus remains with the haemoflagellates, with target product profiles consistent with criteria defined by the WHO and the Drugs for Neglected Diseases Initiative. Two compound series with appropriate oral drug-like properties and curative activity in the acute mouse model of African trypanosomiasis are currently undergoing lead optimisation to obtain cures in the chronic stage of the disease when the parasites have invaded the brain.
The Drug Discovery Unit also has a portfolio of novel targets and mechanisms funded by the Medical Research Council Developmental Funding Pathway Scheme to enhance early-stage discovery of novel therapies for skin, cancer, metabolic and other diseases.
Related news
- Human sleeping sickness parasite sequenced (10 May 2010)
- Gene discovery offers potential for new sleeping sickness treatment (15 May 2009)
- Dundee researchers get £1.7m to tackle trypanosomes (8 October 2008)
