UoA01
Clinical Medicine (UoA 1)
Almost all of the research in this UoA is officially classified as world-leading or internationally excellent in terms of originality, significance and rigour.
The following academic units formed our submission to UoA 01:
- Institute for Ageing and Health (now called Institute for Ageing)
- Institute of Cellular Medicine
- Institute of Genetic Medicine
- Northern Institute for Cancer Research
Our core activity is in translational biomedical research and our key focus is on the health challenges faced by an ageing population:
- understanding their causes
- impacts
In conjunction with academic, clinical and industrial partners, developing effective approaches to address the most significant health issues and implementing novel interventions in practice.
International impact
Our research in this area is making a positive impact on a global scale:
- Diagnosing arthritis in children
- Treating rare diseases
- Pioneering ‘smart’ cancer drugs
- Protecting against mitochondrial disease
The following case studies demonstrate the impact of our research:
Help for cystic fibrosis patients
Help for cystic fibrosis patientsHow better risk stratification for lung transplant has benefitted cystic fibrosis patients
Lung transplants represent the last hope for cystic fibrosis patients with end-stage lung disease.
However, since the mid-1990s, other than in large research centres, some cystic fibrosis patients were not offered this treatment because of the variable and often poor outcome of surgery. This patient group carried a difficult to treat bacterial infection caused by the Burkholderia genus.
In 2001 researchers in Newcastle published findings that demonstrated that one particular species, Burkholderia Cenocepacia, was responsible for the poor outcomes and that other species of Burkholderia were not as dangerous.
This finding was incorporated into international guidelines and since 2008 most transplant centres worldwide have adopted a risk stratification approach to listing patients for transplant.
Consequently, more than 30 people per year worldwide now get transplants that would otherwise have been denied.
Find out more:
Improving patient safety
Improving patient safetyDeveloping gene-guided dosing of warfarin to improve patient safety
Warfarin is an anti-coagulant drug prescribed to tens of millions of people in the UK and US who are at high risk of developing blood clots. Because individual sensitivity to warfarin varies in the population there is a risk of overdosing the drug and causing serious bleeding and even stroke in many people when starting treatment.
In 1999 researchers at Newcastle University were the first to demonstrate a statistically significant link between a person's genotype and the appropriate dose of warfarin. In 2010 the US Food and Drug Administration (FDA) mandated inclusion of a table of dose recommendations based on genotype in the warfarin prescribing information leaflet accompanying the drug.
Newcastle research forms the basis of the 2009 international standard algorithm for gene-guided dosing of warfarin. This approach has been adopted by large US medical centres and the FDA states that it will prevent 17,000 strokes a year in the US.
Find out more:
- Professor Ann Daly
- Professor Farhad Kamali
Uncovering genetic basis of atypical haemolytic-uraemic syndrome
Uncovering genetic basis of atypical haemolytic-uraemic syndromeUncovering the genetic basis of atypical haemolytic-uraemic syndrome leads to improved treatment
Research conducted by Professor Tim Goodship and co-workers at Newcastle has had a profound effect on the prognosis for patients with atypical haemolytic uraemic syndrome (aHUS).
By engaging in research on the genetic factors underlying the disease they developed an understanding of the molecular mechanisms responsible.
Identifying that the majority of patients with aHUS have either acquired or inherited abnormalities of the regulation of complement (part of the immune system) led to the establishment of a UK national service for genetic screening and treatment with the complement inhibitor eculizumab. As Eculizumab is now available to patients in England, the progression to end-stage renal failure can be prevented and patients already on dialysis will soon be successfully transplanted.
Find out more:
Motor neuron disease
Motor neuron diseaseUse of non-invasive ventilation to improve survival and quality of life in patients with motor neuron disease
Motor neuron disease (MND) is a devastating and debilitating disease with poor prognosis; most patients die from progressive respiratory failure within three years of onset. A randomised controlled trial conducted in Newcastle provided robust evidence that non-invasive ventilation for patients with MND can significantly improve quality of life and increase survival (216 days with non-invasive ventilation compared to 11 days without).
Findings from this trial underpinned recommendations concerning the use of non-invasive ventilation in MND in clinical guidelines internationally, and use in clinical practice has increased in the UK, across Europe, and in the US and Australasia.
In the UK, the number of MND patients successfully established on non-invasive ventilation in 2009 had increased 3.4-fold since 2000 and since 2009 has further increased almost two-fold .
Find out more:
Treatments for atopic eczema
Treatments for atopic eczemaIncreased range and adoption of evidence-based treatments for refractory moderate-to-severe atopic eczema
Atopic eczema is a disabling long-term skin condition affecting approximately 2% of the UK adult population.
The mainstay of treatment remains topical steroids and moisturisers, but many adult patients with atopic eczema have resistant disease that can significantly impair quality of life.
Newcastle University researchers conducted clinical trials that showed both whole-body ultraviolet B phototherapy and systemic (tablet) treatment with the immunosuppressant drug azathioprine were effective treatments for adults with atopic eczema resistant to standard topical treatments.
UK and European guidelines written after 2008 recommend UVB phototherapy and azathioprine for atopic eczema, and survey data indicate that both are now widely used to treat the disease in the UK.
Find out more:
Diagnosis of liver fibrosis severity
Diagnosis of liver fibrosis severitySimple non-invasive diagnosis of liver fibrosis severity in Non-alcoholic Fatty Liver Disease (NAFLD)
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the developed world with a prevalence of 20-25% in the general population.
Until Newcastle validated its new diagnostic, the only accurate way to determine the severity of NAFLD was by liver biopsy, an expensive and invasive procedure which is associated with morbidity and occasional mortality.
Studies lead by Professor Day in Newcastle have established a non-invasive fibrosis scoring system, the NAFLD Fibrosis Score (NFS), which is capable of accurately differentiating patients with and without fibrosis. The NFS has now been incorporated into two international guidelines, allows biopsy to be avoided in up to 75% of patients and could save the NHS nearly £2m annually.
Find out more:
Curing chronic granulomatous disease
Curing chronic granulomatous diseaseCuring chronic granulomatous disease in children through early bone marrow transplant
Chronic granulomatous disease is a rare but very serious inherited disorder of the immune system that leaves sufferers vulnerable to potentially fatal bacterial and fungal infections.
Researchers at Newcastle University demonstrated very high survival and cure rates following bone marrow transplantation for the disease and good quality of life for successfully transplanted patients. This led to a change in national clinical policy, and doctors at both specialist disease centres in the UK now recommend transplantation to families where previously they would not have done so.
In the five years prior to 2008 there were only 11 transplants for chronic granulomatous disease in the UK and in the following five years, 36 transplants. 32 children are alive and cured of the disease.
Find out more:
Reducing toxicity of pemetrexed treatment
Reducing toxicity of pemetrexed treatmentReducing the toxicity of pemetrexed treatment in malignant pleural mesothelioma
Malignant pleural mesothelioma (MPM) is a treatable, but incurable cancer that originates in the cell-lining of the lungs. Over 14,000 people worldwide are diagnosed annually with this disease, which is primarily caused by occupational exposure to asbestos.
Antifolates are often used in cancer therapy, but side-effects are a big problem. A retrospective analysis of plasma samples from patients with cancers other than MPM who were treated with the antifolate pemetrexed, in combination with folic acid, determined that homocysteine levels were a good predictor of drug toxicity.
This was simultaneously implemented in a Phase I clinical trial, which showed that pemetrexed was well tolerated by patients with low homocysteine levels. The retrospective analysis also suggested that pemetrexed should be supplemented vitamin B12 as well as folic acid, to reduce drug toxicity.
Ultimately, this permitted the continued development of pemetrexed, which otherwise would have been too toxic for clinical use.
It is now the only licensed drug for MPM treatment, in combination with platinum based chemotherapy.
Find out more:
Treatment of childhood cancer
Treatment of childhood cancerOptimising the treatment of childhood cancer through therapeutic drug monitoring
Clinical pharmacology studies conducted at Newcastle have led to optimisation of the administration of the chemotherapy drug carboplatin in children with neuroblastoma and other cancers.
The research provided the rationale for carboplatin dosing based on patient renal function, with individualised dosing resulting in increased drug efficacy and reduced toxicity.
This approach is now in widespread use in European treatment protocols, benefitting over 2,500 children.
Similar drug monitoring approaches are being implemented for an increasing number of important drugs.
Following a recent Newcastle-led national clinical trial, new dosing guidelines for the drug 13-cis Retinoic Acid have been adopted for high-risk neuroblastoma patients across Europe.
Find out more:
Treatment in children with Neuroblastoma
Treatment in children with NeuroblastomaIdentification of a chromosomal abnormality that is now used to stratify treatment in children with neuroblastoma
Neuroblastoma is a paediatric cancer that arises from the sympathetic nervous system.
The average age at diagnosis is 18 months and the disease accounts for approximately 15% of all childhood cancer-related deaths.
Determining optimal treatment for individual patients is crucial for increasing chances of survival and for reducing side effects of chemotherapy and radiotherapy.
Newcastle-led research identified unbalanced 17q gain as the most common segmental chromosomal abnormality (SCA) in patients with neuroblastoma; this was present in more than 50% of patients.
Gain of 17q is now one of the key SCAs used to determine treatment for patients in a European neuroblastoma trial and in UK treatment centres.
Newcastle research also led to the development of a simple diagnostic test for the detection of the main SCAs in neuroblastoma.
Find out more:
- Dr Nicholas Bown (now at Northern Genetics Service)
Leukaemia survival rates
Leukaemia survival ratesInnovations in the treatment of chronic myeloid leukaemia have almost doubled 5-year survival rates
A new class of drug known as tyrosine kinase inhibitors for the treatment of chronic myeloid leukaemia (CML) has been tested in Newcastle-led international clinical trials.
One of these drugs, imatinib, was found to almost double five-year survival rates and significantly improve quality of life with few side effects.
Subsequent follow up studies found an estimated eight-year overall survival of 85%. Imatinib is now recommended in national and international guidelines and is used increasingly to treat patients with CML.
Find out more:
Diagnostic test for rare muscular disorder type 2A
Diagnostic test for rare muscular disorder type 2ADiagnostic test for the rare muscular disorder limb-girdle muscular dystrophy type 2A
Limb-girdle muscular dystrophy type 2A is a rare (about six cases per million individuals) and incurable muscular disorder with a genetic basis.
Although diagnosis is a multi-step process, which includes symptom assessment and histopathology of affected muscle, it invariably involves measurement of the amount of protein calpain 3 in muscle biopsy samples.
This is performed in diagnostic laboratories worldwide using the two monoclonal antibodies CALP-12A2 and CALP-2C4, which were developed by researchers at Newcastle University in the late 1990s.
In 2009 Newcastle University signed a licensing agreement with an international bioscience company that currently sells the antibodies to institutions worldwide.
Find out more:
- Louise Anderson
- Dr Rita Barresi
- Leica Biosystems
Find out about all our REF 2014 results.