“The unique fusion of individual innovative technologies will provide a novel diagnostic tool leading to a better understanding of the underlying pathophysiology of rare anaemia.”

Lars Kaestner, Coordinator of CoMMiTMenT

Project

Anaemia, which is defined as a haemoglobin concentration less than 11–13 g/dl depending on gender and age, affects 1.6 billion individuals worldwide. Approximately 10% of these individuals are affected by rare anaemia (RA). This disease group includes approximately 90 different types of red blood cell (RBC) diseases, of which 80% are hereditary or congenital in nature. As the pathophysiology of the majority of these RA is poorly understood, the appropriate treatment is often ineffective or even lacking.

There are a substantial number of types of hereditary haemolytic anaemia that are related to abnormalities in the stability and permeability of the plasma membrane to ions; these conditions are, in general, classified according to the alterations in cell morphology. Such conditions include sickle cell disease, α and/or β thalassemia, spherocytosis, elliptocytosis/ovalocytosis, RBC enzymopathies such as phosphofructokinase deficiency (PFK)/Pyruvatekinase(PK) deficiency and other RA that are associated with membrane-related disorders.

Because almost nothing is known regarding the cause of channelopathies in this group of hereditary haemolytic/vasoclusive disorders, they are, in general, often classified as idiopathic and treated symptomatically; diagnostic tools are simply unavailable. Therefore, there is a current demand for new tools for improved diagnosis and monitoring of disease progression.

CoMMiTMenT will facilitate the fusion of non-invasive imaging methods that operate at the molecular level. This goal will be reached by the completely novel combination of OMiCS with SICM. This fusion of technologies is termed µCOSMOS and requires an innovative microfluidic design, optical manipulation and rapid real-time image analysis.

With the proposed novel methodology (µCOSMOS), CoMMiTMenT will identify and characterise the molecular causes of RBC channelopathies and channel-linked disorders and propose personalised pharmacological interventions to counteract the abnormal function of ion transporters. This bench-to-bedside approach will be verified by an accompanying proof-of-concept test (i.e., a clinical study of patients with sickle cell disease).