Blocking blood protein could protect nerves in MS

• Fibrin is a protein that accumulates in the brain in diseases such as MS and Alzheimer’s disease and may play a role in tissue damage, but due to its essential role in blood clotting, successful treatments that can safely block fibrin in the brain without causing undue side effects have remained elusive.
• An innovative study has identified how fibrin is working to help trigger the immune cell attack that leads directly to nerve damage in these types of brain disease.
• They developed a treatment that blocks fibrin in the brain of laboratory models but does not affect blood clotting or normal immune system functions.
• While still in the early stages, if this research can be validated in humans, it may represent the first step in developing a new type of treatment for MS and other diseases.

Fibrin and the immune system

Fibrin is a protein most well-known for its important role in blood clotting. When the body is wounded and starts to bleed, fibrin forms a mesh over the wound site to stop the bleeding. However, fibrin also builds up in the brain during some diseases such as MS and Alzheimer’s disease and the build-up of fibrin is thought to play a role in triggering the immune cell attack in the brain.

MS results from the immune cells attacking the coating around nerve fibres, known as myelin. In relapsing forms of MS, myelin is repaired by the body, leading to the typical pattern of symptoms of MS followed by subsequent recovery. But this process is often incomplete and the nerve fibres are left exposed to further damage. This ultimately results in the accumulation of disability seen in the progressive forms of MS.

Current treatments for MS that only act to stop the immune attacks cannot repair this nerve damage. In a new study published in the prestigious journal Nature Immunology, researchers discovered that fibrin acts as a trigger for the immune system to attack the brain in diseases such as MS. This results in irreversible damage to nerves.

Targeting the action of fibrin

A treatment that targets fibrin and blocks its action would therefore seem to be an ideal solution, but there is a big challenge to overcome – treatments that affect fibrin throughout the body would result in dangerous disruptions to the body’s blood clotting processes. The trick would be to find a way to target the fibrin in the brain without touching the fibrin involved in wound healing.

And in this study, for the first time, researchers have found a way to do just that. They discovered that a particular part of the fibrin protein was exposed when it was interacting with the immune cells in the brain, and crucially, that this was different to the part that is exposed during the blood clotting process. They then screened potential drug molecules to identify one which blocks fibrin in the brain but doesn’t block blood clotting.

They showed that adding this molecule to immune cells and nerve cells together in a laboratory dish prevented the immune cells from damaging and killing the nerve cells. Using three separate laboratory models of MS, the researchers also showed that if they added the molecule before symptoms began, the onset of MS was delayed and the symptoms overall were reduced. Treatment also stopped the immune cell attack on the nerve fibres in the spinal cord, reducing damage, inflammation and loss of myelin. Reassuringly, there was no effect on blood clotting and no effect on the immune system that is needed to fight infections in the rest of the body. In a parallel series of experiments, they showed that this molecule also prevents immune cell damage to the brain in laboratory models of Alzheimer’s disease.

A future new treatment?

This work is very exciting as it reveals an entirely new way to potentially protect nerve cells in the brain and spinal cord. What is needed now is confirmation that this will also work in humans and then testing in clinical trials.

Fibrin accumulation is also a feature of other diseases that do not involve the brain, including rheumatoid arthritis, colitis and Duchenne muscular dystrophy. Future research will need to look at whether these new findings also apply to these other diseases. Treatments that aim to prevent damage within the brain and spinal cord are a huge unmet need in progressive MS and one of the key objectives of the International Progressive MS Alliance.

While still the early stages, findings such as these bring hope that treatments to prevent ongoing damage in MS will one day be a reality.