Brain Atrophy in Secondary Progressive MS Linked in Study to High Levels of Free Hemoglobin in Blood

Hemoglobin leaking from injured red blood cells may be associated with brain atrophy in secondary progressive multiple sclerosis (SPMS), according to researchers at the Imperial College London, U.K.

The study, “Free Serum Haemoglobin Is Associated With Brain Atrophy In Secondary Progressive Multiple Sclerosis,” was published in the journal Wellcome Open Research.

“These are exciting but early results,” Charles Bangham, the study’s lead author, said in a news release. “If further studies confirm them, they may suggest new avenues of treatment, and hopefully more options to offer patients in the future.”

The most common form of multiple sclerosis is relapsing MS, and an estimated 65 percent of these patients will develop secondary progressive MS, a more severe disease form. SPMS is associated with progressive neuronal loss, or brain cell death, leading to brain shrinkage (about 0.3 percent a year) and major disability in patients. Although the mechanisms leading to the development of SPMS are still uncertain, previous studies have suggested that one contributing factor may be iron deposits in the blood vessels of the brain, at amounts high enough to kills neurons.

The researchers wanted to understand whether this brain shrinkage is associated with above-normal protein levels circulating in the blood. To do so, they performed MRI scans to evaluate brain shrinkage in 140 SPMS patients, and compared the results with analyses of protein levels in patients’ blood, taken for a period of two years.

The team also analyzed brain scans and blood samples from 20 healthy individuals, and 40 patients with other medical conditions but not MS.

Results indicated that brain atrophy rates in SPMS patients was linked to increases in the levels of “free” hemoglobin — or hemoglobin that has leaked from blood cells.

Hemoglobin is an iron-containing protein present in the red blood cells that binds to oxygen, carrying it from the lungs to the rest of the body. Previous studies have suggested that MS patients have weak red blood cells that easily rupture and lose hemoglobin. According to the researchers, it is possible that the high levels of free hemoglobin found in SPMS patients may allow more of the protein to cross the blood-brain barrier (a membrane that selects which molecules enter the brain and which don’t, and which is also weaker in MS patients) and enter the brain. Blood levels of free hemoglobin were significantly higher in those SPMS patients with the greatest amount of brain atrophy, the team reported.

Indeed, the researchers estimate that a 30 percent increase in free hemoglobin in the blood can increase the rate of brain shrinkage by 0.1 percent, which, over the years, can significantly affect patient symptoms.

Researchers believe that when hemoglobin enters the brain, it is broken down by an enzyme called heme oxygenase I, which is also found at higher levels in the brains of MS patients, leading to the release of iron.

“The iron escapes from the haemoglobin, and may then result in the cell damage and brain shrinkage we see in secondary progressive MS,” Bangham said.

An iron-poor diet, however, is not a remedy, the researchers emphasized.

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

Rather, Bangham believes that future research should focus on eliminating excess free hemoglobin from the blood.

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