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Projects

Our research focuses on delivering drug discoveries to meet areas of unmet need.

Our research portfolio includes:

AMPA receptors and schizophrenia

Professor Simon Ward researches targets for AMPA receptors to improve cognitive function in schizophrenia.

Addressing the cognitive deficits in schizophrenia is a huge unmet clinical need. Due to the role of AMPA receptors in the cellular processes associated with cognition, we believe that by increasing AMPA receptor function we can improve cognitive function in schizophrenia.

Through work funded by the Wellcome Trust, we aim to use a positive allosteric modulator approach to target AMPA receptors and develop a novel drug that will improve the lives of patients with this mental health condition.

α-GABAA and Huntington’s disease

By targeting GABAA receptors we aim to produce new medications that will improve cognitive function for those with Huntington’s disease.

Neuron

Huntington’s disease is an inherited neurological condition, associated with gradual dysfunction and decline in motor skills, cognitive abilities and behaviour over a twenty year period. The disease ultimately leads to patients needing 24 hour nursing care and is fatal, and there are currently no available treatment options available.

We believe that by targeting subtypes of the α-GABAA receptors in the brain, we can enhance cognition in patients with Huntington’s disease.

Through research funded by the Wellcome Trust, we can provide an answer to this unmet need and improve outcomes for patients with Huntington's disease.

α-GABAA and Anxiety disorders

Anxiety representing one of the world’s biggest mental health problems, by targeting GABAA receptors, we can develop better therapies.

Despite anxiety disorders being the sixth most common cause of disability, there has been no major therapeutic advances since benzodiazepines were introduced in early 1960s, highlighting an urgent need for new and more effective treatments.

Benzodiazepines, commonly known as Valium, are fast-acting but causes sedation in 50% patients. With anxiety representing one of the world’s biggest mental health problems, it is vital that better therapies are developed.

Support from the Medical Research Council is allowing us to investigate targeting subtypes of the GABAA receptors in the brain, to not only improve medications for anxiety but also to reduce unwanted stereotypes.

LIMK1 and Fragile X Syndrome

Professor Simon Ward is investigating how LIMK1 inhibitors can be harnessed to provide effective medications for Fragile X Syndrome.

Fragile X syndrome is the most common single genetic mutation that causes autism, affecting around 1 in 5000 males and 1 in 8000 females. The genetic mutation can cause a wide range of difficulties with learning, as well as social, language, attentional, emotional, and behavioural problems.

The condition is caused by synaptic dysfunction, and previous research has highlighted the role of the LIMK protein in the development of Fragile X. Through funding by the Medical Research Council, we believe that we can look into inhibiting LIMK1 we can develop novel therapies that will impact the lives of people living with the condition.

Bipolar disorder

The Medicines Discovery Institute is finding effective treatments for bipolar disorder by targeting IMPase.

A closeup of some molecular structures.

Lithium is used as a treatment for bipolar disorder, however it can be toxic, requiring blood levels to be closely monitored. This therapy is associated with negative reactions, with 75% of patients taking lithium experiencing side effects.

Lithium works by the inhibiting a protein called IMPase. By finding alternative compounds that inhibit IMPase, we aim to develop an effective treatment for bipolar disorder, but without the side effects experienced with lithium.

By collaborating with University of Oxford and AstraZeneca, and with funding from the Medical Research Council, the Medicines Discovery Institute aims to uncover new lead compounds that will interact with IMPase. These new molecules will act as the starting points for drugs that will greatly improve therapeutic options for patients with bipolar disorder.

NEAT1 and motor neurone disease


Abnormal regulation of the NEAT1 in cells can predispose people to a wide range of diseases, including motor neurone disease, and represents a promising target for new therapies.

NEAT1 is a non-coding RNA involved in many diseases such as cancer and neurological disease. The Medicines Discovery Institute aims to understand the role of the two forms of NEAT1 in disease, testing new therapeutics that will modify levels of NEAT1 in cells, including neurons.  This research will address areas of unmet medical need and improve therapies for a range of diseases in the future.

Serine Racemase Inhibitors and Treatment Resistant Depression

Major depressive disorder is the second leading cause of disability globally, with one third of all patients not responding to current treatments. Anti-depressant drugs such as serotonin-reuptake inhibitors are the standard treatment for major depressive disorder, but over 30% of patients will not respond to these medications.

By inhibiting serine racemase, which interacts with NMDA receptors in the brain, we hope to produce a more effective therapeutic option for patients living with treatment resistant depression

Serine Racemase Activators and Schizophrenia

Schizophrenia is a psychiatric disorder that affects about 1% of the world population and is characterised by psychosis, cognitive impairment and social withdrawal. Current therapeutic options for schizophrenia fail to treat several of the symptoms of the condition, highlighting an urgent need for new treatments.

Altered function of the NMDA receptors in the brain has been linked with schizophrenia and provides a potential target for improved therapies. By activating serine racemase, we believe we can improve the function of NMDA receptors in schizophrenia, and develop an effective treatment for this condition.

Oncology

Professor Simon Ward’s lab aims to identify novel targets to personalise cancer treatments.

Through funding provided by the Wellcome Trust, we are working to develop an integrated target validation and drug discovery platform for the identification of novel agents targeting genome stability for the treatment of cancer.

We aim to personalise cancer treatment, by targeting medicines based on the individual tumour, and also reduce the side effects experienced during cancer therapies.