Project Details

Early Career

Status: Funded - Open

Investigating the role of extracellular matrix remodeling in oedematous severe acute malnutrition: A validation study

Gerard Gonzales, BSc, MSc, PhD

Summary

BACKGROUND: The primary cause of severe acute malnutrition (SAM) is lack of sufficient quantity and/or quality of food to meet metabolic demands of normal growth and fighting infections. However, the pathophysiology and aetiology of oedematous SAM, a.k.a kwashiorkor, remains enigmatic and mainly descriptive.

GAP: Kwashiorkor children are notoriously difficult to manage leading to higher mortality rates. Several hypotheses on the cause of kwashiorkor have been proposed, most popularly hypoalbuminemia, toxins and microbiome, but none have been substantiated by strong clinical and/or pre-clinical evidence.

HYPOTHESIS: Our hypothesis is that kwashiorkor is associated with extracellular matrix remodeling leading to a fibrotic phenotype.

METHODS: Our proposed study is a validation of our preliminary investigation whereby biomarkers related to extracellular matrix remodeling and metabolome alterations, following proteomics and metabolomics analyses, were found. We envisage to validate our multi-omics results by looking deeper into clinically relevant biomarkers of fibrosis using validated immunoassay techniques on an independent cohort of children with SAM.

RESULTS: Pending.

IMPACT: Understanding the pathophysiology of kwashiorkor is the first step in developing effective strategies to alleviate the condition of the affected children and reduce their risk of death. Results of this study will provide new therapeutic targets for kwashiorkor.