Approved research

Haemoglobin in multiple sclerosis (HIMS) study

Lay summary

Multiple sclerosis (MS) is a common cause of non-traumatic disability in young adults. It is associated with damage to the brain and spinal cord, causing many different symptoms such as with cognition, vision, movement, coordination, bladder control and sensation. MS is triggered by an immune attack against the brain and spinal cord. However research suggests that haemoglobin, the red pigment in red blood cells, may play an important role in determining the extent of damage. There is some evidence that red blood cells are more fragile in people with MS, releasing haemoglobin from the cells. Haemoglobin or its breakdown products such as haem and iron are toxic once outside the red blood cells, may enter the brain in MS and thereby contribute to nerve injury. Several thousand UK Biobank participants have a diagnosis of MS. Control individuals with no neurological disease are easily selected from amongst the other participants. In this project we will address the hypothesis that red blood cells are more fragile in people with MS, compared to control individuals. We will investigate whether this is linked to accumulation of iron in the brain, to brain volume and number of MS brain lesions, and to clinical outcome. Brain iron, volume and lesion number will be measured from brain magnetic resonance images. Clinical outcome will be assessed using a number of domains including thinking, physical activity, employment, and other social and health outcomes. We will also study whether genes associated with red blood cell fragility are related to brain imaging and clinical outcome, in people with MS. Dehydration is not uncommon in people with MS, and we will study this by comparing their fluid intake and urinary salt concentration, with those in control individuals. We will study whether dehydration is associated with increased red blood cell fragility. The body has created multiple systems to protect itself from haemoglobin and its breakdown products; each system consists of multiple proteins working together. The genes that code for proteins that mitigate the toxicity of haemoglobin and its breakdown products can vary such that the toxic effects will vary from patient to patient. We will investigate whether this genetic variation is associated with disease outcome in people with MS. This study will deliver new insights which may lead to new treatments for MS. It will provide two students, working under close supervision, with experience in research and scientific publications to further their careers.