Research Moves Closer to Finding Cause of Multiple Sclerosis

Mitochondria take center stage

An international team at the University of Exeter Medical School in the United Kingdom and at the University of Alberta in Canada has discovered an underlying defect in brain cells that may lead to multiple sclerosis (MS), providing a potential target for future treatments. The new study was published in the journal Neuroinflammation.

Investigator Professor Paul Eggleton of the University of Exeter said: “Multiple sclerosis can have a devastating impact on people’s lives, affecting mobility, speech, mental ability, and more. So far, all medicine can offer is treatment and therapy for the symptoms. As we do not yet know the precise causes [of the disease], research has been limited. Our new findings have uncovered a new avenue for researchers to explore.”

MS affects approximately 2.5 million people worldwide. Typically, patients are diagnosed in their 20s and 30s, and the disease is more common in women than in men.

MS causes the body’s own immune system to attack myelin––the fatty sheaths that protect nerves in the brain and spinal cord. This leads to brain damage, reduced blood and oxygen supplies, and the formation of lesions throughout the body. Symptoms may include muscle spasms, mobility problems, pain, fatigue, and problems with speech.

Scientists have long suspected that mitochondria––the energy-creating “powerhouse” of cells––play a key role in the development of MS.

The Exeter–Alberta team was the first to combine clinical and laboratory experiments to explain how mitochondria become defective in people with MS. Using human brain tissue samples, they found that a protein called Rab32 is present in large quantities in the brains of people with MS, but is virtually absent in healthy brain cells.

When Rab32 was present, the team discovered that the endoplasmic reticulum (ER)––the part of the cell that stores calcium––gets too close to the mitochondria. The resulting miscommunication with the calcium supply triggers the mitochondria to “misbehave,” the investigators said, ultimately leading to toxicity in the brain cells of people with MS.

The researchers don’t yet know what causes the influx of Rab32 in brain cells, but they believe the defect could originate at the base of the ER organelle.

The new finding will enable scientists to search for effective MS treatments that target Rab32 and to embark on determining whether other proteins may play a role in triggering MS, according to the researchers.

Source: University of Exeter; April 24, 2017.