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Connective tissue disease

A connective tissue disease is defined as a disease which affects the connective tissues of the body.

Overview:

Systemic Lupus Erythematosus (SLE) and connective tissue disorders (CTDs) affects approximately 50-60,000 individuals in the UK, usually young women. The diseases share many overlapping clinical features and common aetiopathogenic factors. This family of disorders are associated with excess morbidity and mortality across the patient’s life-span. There is a lack of proven therapies available.

Issue:

A number of targeted therapies for SLE and CTDs have been disappointing in controlled clinical trials despite open label evidence of efficacy. However, initial subsetting of patients has suggested that greater efficacy is seen in more related subgroups of patients. Targeted therapies for SLE and CTDs are likely to be effective across subjects with shared immunopathogenesis rather than simply based on clinical criteria achieved. A number of co-morbidities are also common to this family of conditions including premature cardiovascular disease, neurocognitive impairment / fatigue, and poor pregnancy outcomes.

What we aim to achieve:

We plan to determine how to better subset patients, using next-generation sequencing (NGS) and genome wide association studies (GWAS), into groups with susceptibility related to common biological pathways, and to assess novel targeted therapies to these more coherent patient subsets. We will also study how markers of adverse outcomes vary with disease activity and use these as additional outcomes measures. Studying the immune/inflammatory pathways associated with pregnancy outcomes using this parallel approach will allow us to target early immunological and vascular events to improve placental development in these patients.

In the next 5 years we will achieve the following benefits for patients:

  • Improved understanding of immunopathogenic subsets of SLE and CTD as a platform for more targeted therapeutic interventions.
  • A focused assessment of cardiovascular and neuropsychiatric health in SLE patients using validated biomarkers.
  • Improved understanding of the association of inflammation with additional outcomes of direct relevance to patients including cardiovascular risk, fatigue and cognition.
  • Improved screening and assessment of pregnancy risk for improved fetal-maternal outcomes.

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