Arginine research in MELAS syndrome

Research type

Clinical research

Start date

01/07/2016

Introduction

MELAS syndrome (Mitochondrial encephalomypathy, lactic acidosis, and stoke-like episodes) is one of the most occurring mitochondrial metabolic diseases. Mitochondria are the power plants of the cells to provide cellular energy. It can develop at any age and is associated with severe neurological defects, like epilepsy, dementia, migraine or psychiatric problems. Other defects (incl. cardiac failure, renal failure, diabetes, loss of hearing) often occur as well.

Description research

The neurology and anesthesiology department in the Erasmus MC Rotterdam work together on mitochondrial oxygen availability in patients with MELAS syndrome treated with Arginine.  In a few small studies research is done on the Arginine effects. The symptoms seem to improve, but the real working mechanisms are still unclear. Arginine should improve the blood supply and as a result the oxygen availability in the tissues.
 
In MELAS syndrome patients mainly two processes create a misbalance between the energy demand and the energy supply on a cellular level.  First due to a genetic defect in the mitochondria the energy production in other words the oxidative phosphorylation is working suboptimal. Therefore the cells lag of available energy. Second the blood supply towards the tissues, the micro vessels, are not regulated in a proper manner due to a disturbed NO (nitrogen oxide) production.
 
Arginine will mainly improve the blood supply with available oxygen on a cellular level. This may improve the unbalance in energy demand en supply. The energy unbalance will first express in organs with a high-energy demand such as the brain.
 
The two processes both have an effect on the mitochondrial oxygen supply and consumption. With a new available measurement technique “COMET” Cellular Oxygen METabolism monitor it is possible to measure in vivo non-invasive mitochondrial oxygen availability in time. This technique can be used in patients with the MELAS syndrome to investigate the oxygen delivery and potentially the effects of Arginine.