Clinical research trial PKAN started
Pantothenate Kinase-Associated Neurodegeneration (PKAN) is an ultra-rare neurodegenerative disease (prevalence of 1 case per 1-3 million), caused by mutations in the genetic material, called the PANK2-gene. Patients suffer from progressive movement disorders, in particular generalized dystonia and parkinsonism, although other symptoms can also occur, such as cognitive impairment and psychiatric problems.
A characteristic MRI pattern in the brain is found in PKAN patients, caused by iron accumulation in the basal ganglia. PKAN often presents itself at a young age (around 2 years of age) and the symptoms progress rapidly. Patients at a young age initially suffer from mild symptoms, such as delayed development and poor balance, but within 5-10 years patients lose their ability to move independently. In exceptional cases PKAN symptoms arise during adolescence. To date, no effective treatment exists for this severe brain disorder.
The laboratory run by Professor Sibon at the UMCG has, among others, conducted extensive research into the mechanism of PKAN, predominantly in fruit flies. The PANK2 gene encodes an enzyme pantothenate kinase 2, which is in turn required to convert vitamin B5 into coenzyme A (CoA). The end product, CoA, is required for normal metabolism in our bodies. A downstream metabolic product from this conversion into CoA is called 4’-phosphopathetheine (4’-PPT). In PKAN patients, 4’-PPT and therefore CoA are not properly produced. The idea is that, by administering additional 4'-PPT to PKAN patients, their deficiency of CoA is compensated. In PKAN animal models, 4'-PPT was indeed found to have a beneficial effect.
In September 2021, we started our clinical trial with 10 Dutch and Belgian PKAN patients. Throughout the two year trial these patients receive the vitamin supplement 4’-PPT in varying doses. Our research focusses on the effect of the 4’-PPT supplement on several parameters in the patients’ blood, while monitoring safety and tolerability. The study is subsidized by ZonMw/ Hersenstichting, dossier number 40-44600-98-323.