Drug Discovery at the Wolfson Centre for Age-Related Diseases
Scientists in the Wolfson Centre for Age-Related Diseases (CARD) are involved in numerous drug discovery programs. We sit on the scientific advisory boards and act as consultants for biotech and large pharmaceutical companies; this gives us an unparalleled insight into what small and large companies do well, and how best academics can contribute to drug discovery. Some of our scientists are pioneering pre-clinical studies using biopharmaceuticals - for example the Bradbury lab are leading on the development of an enzyme treatment for spinal injury, and the Moon and Duty lab are pursuing the use of growth factors for stroke and Parkinson's disease. We summarise below some of our funded activities that aim to repurpose small molecule drugs for Alzheimer's and Parkinson's disease, and develop new ones for these and other conditions.
Repurposing drugs for Dementia
Developing a new drug can cost hundreds of millions of pounds and this tends to focus on the use of that drug for a specific condition. What if a drug that is approved for use for one condition could be used to treat another condition, especially one where there are no effective drugs available? This is called "repositioning" or "repurposing" and it offers the potential of finding new treatments for conditions like Alzheimer's disease relatively quickly at a fraction of the usual cost. Scientists in the CARD are using bioinformatics approaches developed by Dr Gareth Williams to determine if they can repurpose existing drugs for Alzheimer's and Parkinson's disease with support provided by the Wellcome Trust and Safra foundation.
Informatics led drug discovery - new "hits" for tinnitus
Tinnitus is often described as "ringing in the ear" and is a condition that sometimes can have a serious impact on life, causing insomnia and depression. CARD scientists Doherty and Williams have been working with a Swiss company (see Auris Medical Collaboration) to develop new drugs to treat this condition, drawing on our expertise in virtual drug screening methodologies. This involves identifying a key therapeutic target and using the power of computing to identify small molecules that can be developed into effective drugs. The CARD also hosts Professor Karen Steel's lab. Karen is a renowned expert on the genetics of deafness, with efforts in her lab now turning to drug discovery programs to combat age-related hearing loss. She is also collaborating with Professor Peter McNaughton to investigate a potential drug treatment for tinnitus.
Bench to Bedside - the retinoid drug discovery program
Retinoids are small molecules that act as agonists leading to transcriptional outputs by activating retinoic acid receptors (RARs). Deficits in retinoid signalling have been implicated in neurodegenerative diseases including Alzheimer’s disease (AD) and a lack of retinoid signalling prevents axonal regeneration in spinal cord injury (SCI). Professor Jonathan Corcoran and Dr Maria Goncalves have developed a lead RARa drug for the treatment of AD and a RARb clinical candidate for the treatment of SCI which is now approved for Phase I trials.
Pain research - from target validation to drug discovery
Pain remains a significant problem and is often poorly treated in the clinic. Existing drugs have a range of unpleasant and even dangerous side effects. The McNaughton lab have discovered that an ion channel called HCN2, which spans the cell membrane and allows electric current to enter nerve cells, is critical for initiating pain. This work suggests that blockers of HCN2 ion channels will be potent analgesics, but the drugs must be highly selective because related ion channels are important in setting the heart rate. This drug development programme, supported by the Wellcome Trust, seeks to develop potent and selective HCN2 blockers and to show that these are effective analgesics in humans.