Unsteady hands, stiff muscles and slow movements are all typical symptoms of Parkinson’s disease. Some 220,000 people in Germany, and one million people in the U.S., are affected by the disease. Caused by the loss of nerve cells in the brain and occurring more frequently as people get older, Parkinson’s remains incurable. Now a team of researchers in Germany, headed by Dr. Dr. Michela Deleidi at the Hertie Institute for Clinical Brain Research and the University of Tübingen, report that nicotinamide riboside (NAD) – a form of vitamin B3 – may offer a possible treatment. Initial results from the laboratory are promising:
“This substance stimulates the energy metabolism in the affected nerve cells and protects them from dying off,” Deleidi explains.
The researchers have published their study in the latest edition of the journal Cell Reports.
Damaged Mitochondria Lead to Cell Death
It is still not clear precisely what leads to the development of Parkinson’s, but scientists do know that nerve cells in the substantia nigra region of the brain die off. Recently it has been recognized that the mitochondria in these cells are damaged. Mitochondria are responsible for producing energy, making them the mini-power house of the cell. When they go wrong, the cell may die. “In our study we aimed to investigate whether damaged mitochondria were merely a side effect, or whether they cause Parkinson’s disease,” says Deleidi.
To find out, the researchers took skin cell samples from patients with Parkinson’s disease. They converted the skin cells into stem cells and then into nerve cells. The cells had a defect of what’s known as the GBA gene – the most frequent risk gene for Parkinson’s. Just like the ‘real’ nerve cells, their mitochondria – and consequently their energy production – were impaired.
Overhaul of Cellular Power Houses
The researchers then sought to stimulate the formation of new mitochondria. The coenzyme NAD plays and important role in mitochondrial function and energy production. The researchers ‘fed’ the cells nicotinamide riboside, a form of vitamin B3 and a precursor of the coenzyme. This led to a rise in the concentration of NAD in the cells. The result:
“The nerve cells’ energy budget improved considerably. New mitochondria formed and energy production rose.”
In order to observe the effect of the vitamin in a living organism, the researchers took the further step of investigating flies with a GBA gene defect. As with Parkinson’s patients, the flies’ dopamine-rich nerve cells died off, and as they aged, the flies had increasing difficulties in walking and climbing. Deleidi and her colleagues divided the flies into two groups. One group received feed enriched with the vitamin, the other did not. “The substance had a positive effect here as well. In the flies that were treated, far fewer nerve cells died off.” Furthermore, they retained their mobility longer.
“Our results suggest that the loss of mitochondria does indeed play a significant role in the genesis of Parkinson’s disease,” Deleidi summarizes. “Administering nicotinamide riboside may be a new starting-point for treatment.” Further studies are needed to determine whether the vitamin can be of real help for patients with Parkinson’s disease. The researchers are planning to test the effects of nicotinamide riboside on patients. Other studies have shown that it is well tolerated by healthy test subjects and have potential beneficial effects on cardiovascular health,” Deleidi says.
Source: The NAD+ precursor, nicotinamide riboside, rescues mitochondrial defects and neuronal loss in iPSC and fly models of Parkinson’s disease, Cell Reports, DOI: 10.1016/j.celrep.2018.05.009