AdoCbl is one of the active forms of vitamin B12 which inhibits kinase activity of LRRK2 enzyme and prevents the neurotoxicity in Hereditary Parkinson's in cultured cells of primary rodents and in many genetically modified models, according to a new research conducted by Iban Ubarretxena, the Ikerbasque researcher and director of the Biofisika Institute at the UPV/EHU's Science Park together with an international research team, published in the journal Cell Research.
Parkinson's is the most common, chronic neurodegenerative movement disorder affecting 1% of the global population over seventy years of age. Right now, there is no cure for this disease and the available treatments focus on addressing its symptoms but not its progression.
‘Vitamin B12 is the new modulator of the kinase activity of LRRK2. It could act as a basis to develop new therapeutic strategies to fight hereditary parkinson's associated with pathogenic variants of the LRRK2 enzyme.’
Although most cases of Parkinson's are sporadic, the inheritable variants of the disease are mainly associated with mutations of the gene that encodes the LRRK2 enzyme. In 2004 an international research team, in which researchers from the Basque Country participated, established the link between one of the mutations in this enzyme and patients diagnosed with the disease.
So the LRRK2 enzyme, which is also known internationally by the name "dardarina", the Basque word that means tremor, has become one of the most attractive therapeutic targets for developing new drugs to combat inheritable Parkinson's.
Neurotoxicity, or the pathogenic effects as a whole associated with LRRK2, is mainly due to the fact that pathogenic mutations increase the kinase activity of this enzyme, which has prompted an international race to develop inhibitors. Right now, specific, powerful inhibitors of the kinase activity of LRRK2 do in fact exist. Yet many of them cause undesirable side effects or produce very unclear clinical results.
So according to the study, vitamin B12 has turned out to be a new class of modulator of the kinase activity of LRRK2, which, as Iban Ubarretxena pointed out, "constitutes a huge step forward because it is a neuroprotective vitamin in animal models and has a mechanism unlike that of currently existing inhibitors. So it could be used as a basis to develop new therapies to combat hereditary Parkinson's associated with pathogenic variants of the LRRK2 enzyme".