World Multiple Sclerosis Day: ERC funded research
Multiple sclerosis (MS) is one of the most common neurological disorders. The WHO estimates that MS affects 2.5 people per 100,000 worldwide. This picture is an uneven one: Europe has the highest incidence of MS, with 80 sufferers per 100,000. MS can occur at any age, women are twice as likely to develop the disease as men. MS can be relatively benign, but it can also devastate the body: leading to the loss of the ability to write, speak, or walk. Symptoms include numbness and tingling; blurring of vision; problems with mobility and balance; muscle weakness or spasms; fatigue.
No-one fully understands what causes MS. The only consensus is that the immune system becomes hyperactive, attacking the myelin sheath that surrounds the brain's functional cells (neurons). Myelin protects the neurons from damage, and acts as a transmitter of electrical impulses along the nerves. MS causes an inflammation of myelin, and results in scarring.
Researchers have found that certain genes have a role to play in MS. But environmental factors are also significant: low levels of Vitamin D are thought to increase the likelihood of developing the disease. Because no-one has identified the triggers for MS, there is no treatment which can "cure" the disease. The drugs available aim to alleviate symptoms or reduce the number and severity of relapses, but none of these treatments can do anything for patients with the most severe form of the disease. Stem cell therapy offers some hope, but its progress has been slow. Stem cells reboot the immune system, and in doing so eradicate the mechanism that causes MS. Trials so far have proved them to be effective with patients whose disease has proved resistant to other forms of therapy. But they cannot yet reverse nerve damage: for patients with advanced MS the damage is too extensive to be treated.
Some ERC projects in this field
Arresting the destruction of the myelin sheath
T cells, a type of white blood cells, attack foreign invaders and diseased or damaged cells as part of the body's immune response. In MS, the migration of these T cells across the blood brain barrier (BBB) causes the T cells to identify the myelin coating of the nerves as "foreign", resulting in inflammation and myelin damage. By studying the mechanisms that cause this inflammation, the team aims to assess the potential therapeutic benefits for MS patients of inhibiting T cells trafficking in the central nervous system (CNS). By examining the effects of blocking these inflammatory processes in animal models suffering from autoimmune encephalomyelitis (EAE), an animal model of MS, Dr Constantin's team hope to be able to enlarge our understanding of the immune system's role in neurological diseases.
Grantee: Prof Gabriela Constantin
Host Institution: University of Verona (Italy)
ERC Project: Molecular mechanisms controlling leukocyte trafficking in the central nervous system (NEUROTRAFFICKING)
ERC Call: Starting Grant 2010
ERC Funding: €1.2 million for four years
Reversing damage to the myelin sheath
This project investigates the process by which myelin is formed molecularly. In MS patients, the neuron to myelin signalling system is impaired, resulting in inefficient myelination and progressive neurodegeneration. When the CNS develops, cells called oligodendrocytes form around the nerves and provide insulation. This insulation is vital for the neurons to metabolise, and conduct signals effectively. This project aims to develop means to promote remyelination by understanding how the body's signalling network acts in concert with the cells' ability to produce myelin. The research team has succeeded in defining the role of the diffusion barrier in the formation of myelin. This barrier acts to prevent the incorporation of large proteins into the myelin membrane sheets: this discovery explains the high proportion of lipids present in the myelin sheets. These lipids are crucial for the electrical insulation of nerve cells. The goal is to find new drug targets for remyelination.
Grantee: Dr Mikael Simons
Host Institution: Max-Planck Institute for Experimental Medicine, Göttingen (Germany)
ERC Project: Mechanisms of myelin biogenesis and repair (MYELIN)
ERC Call: Starting Grant 2007
ERC Funding: € 1.3 million for four years
Stem cell therapy as a treatment for MS
This project looks at stem cells' potential as a treatment for MS. Rather than approach stem cells as a replacement for lost or damaged cells, the research team focuses on the ability of neural stem cells/ precursor cells (NPCs) to repair a damaged nervous system. Scientists know very little about how NPCs work. Dr Pluchino examines the ramifications of a novel inter-cellular communication mechanism, in which cell membranes (membrane vesicles, or MVs) are passed from donor to recipient cells. Understanding how this communication occurs will allow the team to identify both its molecular makeup and its therapeutic benefits. Using computational analysis, bioinformatics techniques and rodent models, this project hopes to determine how stem cell behaviour can be translated into treatments for neurological disorders.
Grantee: Dr Stefano Pluchino
Host Institution: University of Cambridge (UK)
ERC Project: Secreted membrane vesicles: role in the therapeutic plasticity of neural Stem cells (SEM_SEM)
ERC Call: Starting Grant 2010
ERC Funding: € 1.5 million for five years