Brain Shrinkage in Multiple Sclerosis Associated With Leaked Protein from Damaged Red Blood Cells

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Highlights

• Brain damage in multiple sclerosis may be associated with hemoglobin leaking from damaged red blood cells (RBCs).
• Lower levels of hemoglobin could slow multiple sclerosis disease progression.
• Secondary progressive multiple sclerosis causes brain cells to die.

Leaked protein from the damaged red blood cells may be linked to brain shrinkage in multiple sclerosis (MS). The study was conducted by a team from the Imperial College London.

Professor Charles Bangham, lead author of the study from the Department of Medicine at Imperial, said: "These are exciting but early results. If further studies confirm them, they may suggest new avenues of treatment, and hopefully more options to offer patients in the future."

‘Blood levels of "free hemoglobin� - hemoglobin that has escaped from the red blood cells - were higher in multiple sclerosis (MS) patients with the greatest amount of brain shrinkage.’

Secondary Progressive Multiple Sclerosis

• 65% of the MS patients develop secondary progressive multiple sclerosis (MS), a more severe form of the disease. Secondary progressive MS starts 15 years after the initial MS diagnosis. The symptoms become steadily worse with no signs of improvement.
• On average, the brain shrinks by about 0.3 percent a year in secondary progressive MS.
• High amounts of iron are deposited around the brain's blood vessels.
• Although iron is crucial for the bodies to function normally - high levels pose toxic health risks.
• This might be the reason for the death of brain cells in patients with MS.

Role of Hemoglobin in Multiple Sclerois

In MS condition, when the red blood cells break down they release hemoglobin into the blood stream. Hemoglobin is prevented from entering the brain by a checkpoint called the blood-brain barrier between the bloodstream and the brain. However in MS patients the checkpoint is weakened allowing the hemoglobin protein to enter the brain.

The hemoglobin which entered the brain is broken down by haem oxygenase I enzyme which is found in high levels in the brains of patients with multiple sclerosis. The iron molecule escapes from the hemoglobin protein resulting in cell damage and brain shrinkage as seen in secondary progressive MS. The team also found high levels of a compound called serum lactate dehydrogenase in MS patients, which is released when red blood cells disintegrate.

"Iron eaten in foods has no effect on the levels of iron that accumulate in the brain. It is the hemoglobin levels, rather than iron that needs to be tackled. Iron is vital for the body, and should not be reduced in the diet," said Professor Bangham.

Study

The scientists collected blood samples from the following

• 140 patients with secondary progressive MS - the patients were a part of a clinical trial examining the effect of statins on secondary progressive MS. The trial showed statins may have a beneficial effect on brain shrinkage, although this doesn't seem to be linked to hemoglobin levels.
• 20 healthy controls.
• 40 patients with other medical conditions.

and looked for proteins raised above normal levels.

Scientists found that a 30 percent increase in free hemoglobin levels resulted in an increased rate of brain shrinkage by 0.1 percent.

Professor Bangham explained that the findings were unexpected: "We were amazed by the results, and we were surprised by the size of the apparent effect of hemoglobin on brain shrinkage. Over a number of years it could significantly impact a patient's symptoms. He added that high hemoglobin levels are not the only factor leading to brain shrinkage, but could be a significant contributor".

Existing trials are testing potential MS treatments that mop up excess iron. Professor Bangham questions whether this is the best approach.

"It may be more effective to look at ways of removing excess hemoglobin from the blood, rather than iron. There are a number of drugs that do this, although none have been used for multiple sclerosis."

The team is now working on further studies to confirm the findings, and explore what treatments may tackle high levels of hemoglobin in the blood.

Multiple Sclerosis

• Multiple sclerosis (MS) a nervous system disorder affects the brain and spinal cord.
• MS damages the myelin sheath - the material that surrounds the brain and protects the nerve cells.
• Symptoms of MS include visual disturbances, muscle weakness, trouble with coordination, thinking and memory problems.
• In the US, the number of people with MS is about 400,000, with 10,000 new cases diagnosed every year.
• MS is more common in females than males.
• Caucasians especially those of European or Scandinavian ancestry are at a greater risk of MS than those of African heritage.
• It is diagnosed in people between the ages of 20 and 50 years.
• There is no cure for multiple sclerosis.

The findings have been published in Wellcome Open Research

References

1. Multiple Sclerosis - ( https:medlineplus.gov/multiplesclerosis.html)
2. Information on Multiple Sclerosis - (http://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/home/ovc-20131882)
3. Multiple Sclerosis - Frequently Asked Questions - (http://mymsaa.org/ms-information/faqs/)

Source: Medindia

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