Title: Understanding CDA-I pathogenesis to improve diagnosis and treatment
Funder: Action Medical Research

Abstract: Background_x000D_ Congenital dyserythropoietic anaemia type 1 (CDA-1) is a severe, inherited anaemia affecting an estimated 30,000 to 40,000 patients worldwide. Anaemia occurs when the blood contains too few red blood cells and therefore cannot carry enough oxygen around the body. The main symptoms include weakness, tiredness, shortness of breath and persistent headache. CDA-1 is usually diagnosed in childhood but often affects babies even before they are born. Current treatments include blood transfusions and injection with a medicine called interferon-alpha. Blood transfusions are time consuming, carry a risk of infection and can lead to a build-up of iron within the body causing additional complications. Interferon treatment is not always effective and often also causes a number of unwanted effects. _x000D_ _x000D_ The research project_x000D_ This project aims to gain a better understanding of the causes of CDA-1 by looking at specific pathways within cells. The team will investigate how gene mutations found in children with CDA-1 change the behaviour of the proteins involved. They will also determine exactly how this process is affected by interferon and why this leads to improved production of red blood cells. The researchers will use this information to investigate a better tolerated and more effective treatment for CDA-1. In the short term this work will lead to improved diagnosis, in the medium term understanding how interferon works will help researchers develop safe and effective medicines for CDA-1. In the longer term, finding drugs to improve red blood cell production could help a large number of patients worldwide who are affected by other types of anaemia._x000D_ _x000D_

Lay abstract: Background_x000D_ Congenital dyserythropoietic anaemia type 1 (CDA-1) is a severe, inherited anaemia affecting an estimated 30,000 to 40,000 patients worldwide. Anaemia occurs when the blood contains too few red blood cells and therefore cannot carry enough oxygen around the body. The main symptoms include weakness, tiredness, shortness of breath and persistent headache. CDA-1 is usually diagnosed in childhood but often affects babies even before they are born. Current treatments include blood transfusions and injection with a medicine called interferon-alpha. Blood transfusions are time consuming, carry a risk of infection and can lead to a build-up of iron within the body causing additional complications. Interferon treatment is not always effective and often also causes a number of unwanted effects. _x000D_ _x000D_ The research project_x000D_ This project aims to gain a better understanding of the causes of CDA-1 by looking at specific pathways within cells. The team will investigate how gene mutations found in children with CDA-1 change the behaviour of the proteins involved. They will also determine exactly how this process is affected by interferon and why this leads to improved production of red blood cells. The researchers will use this information to investigate a better tolerated and more effective treatment for CDA-1. In the short term this work will lead to improved diagnosis, in the medium term understanding how interferon works will help researchers develop safe and effective medicines for CDA-1. In the longer term, finding drugs to improve red blood cell production could help a large number of patients worldwide who are affected by other types of anaemia._x000D_ _x000D_

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: BLOOD