Cell biologists discover possible treatment for rare neurodegenerative disease PKAN

Cell biologists at the University Medical Center Groningen/University of Groningen have made an important discovery that may lead to a treatment for patients with the serious neurodegenerative disease PKAN. The researchers, headed by professor Ody Sibon, have found a synthetic substance (pantethine) that in fruit flies stimulates the extra production of Coenzyme A in the body. Coenzyme A eases the symptoms of PKAN. Sibon will be publishing her research today in the renowned scientific journal Proceedings of the National Academy of Sciences (PNAS).

PKAN (Pantothenate Kinase-Associated Neurodegeneration) is a serious hereditary disease whose symptoms typically begin in childhood. It is a very painful disease characterized by a swift degeneration in the ability of the limbs to coordinate movement. Patients are less well able to walk, they stumble a lot, suffer from very powerful and painful contractions of the muscles in the back and limbs, have problems with talking and swallowing. These symptoms get worse as the patients grow older and never vanish. Patients often die young. As yet there is no treatment for the disease.

Research results

Patients who suffer from PKAN are carriers of a defective gene, the pantothenate kinase gene. If this gene is defective, then the pantothenate kinase enzyme is not working at all or not working properly. This enzyme is needed in the body to make Coenzyme A. In its turn, Coenzyme A is needed for all kinds of metabolic processes in the cells in our bodies.
In her research, Sibon demonstrates that a defective pantothenate kinase gene really does lead to low levels of Coenzyme A. The synthetic substance pantethine ensures that Coenzyme A levels rise again, and this has a protective effect in fruit flies and leads to an improvement in the symptoms. Adding pantethine to the food of the fruit flies with PKAN resulted in an increased life span, increased ability to climb and that the brains of the ‘sick’ flies looked better.
In addition, Sibon’s research revealed that pantethine works in cultivated human cells where the human pantothenate kinase gene has been disabled; pantethine thus not only works in fruit flies, but also in human cells. The results of this research are not only very hopeful because they demonstrate that it may be possible to develop a simple therapy for PKAN patients, but also because they show that there is a previously unsuspected way of making Coenzyme A.

Research with fruit flies

The breakthrough was achieved thanks to research conducted on fruit flies. These tiny creatures have the same characteristics as humans with regard to the essential basic mechanisms needed to live a healthy and long life. This makes fruit flies perfect for conducting research aimed at better understanding diseases.

This research was partly financed by a VIDI grant from ZonMW that Ody Sibon received in 2003.