Folinic acid therapy in patients with Kearns-Sayre syndrome (KSS) and cerebral folate deficiency - mitoFolat

• Applicant: Professorin Dr. Jutta Gärtner
• Subject Area: Pediatric and Adolescent Medicine
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 432668322

Kearns-Sayre syndrome (KSS) is a progressive neurodegenerative disorder, which leads to subsequent loss of motor and cognitive skills, fever-triggered crises and early death. De novo single large-scale mtDNA deletions and/or duplications are the genetic hallmark. KSS is associated with cerebral folate deficiency, which is characterized by low cerebrospinal fluid concentrations of the active folate metabolite 5-methyltetrahydrofolate (5MTHF) in cerebral spinal fluid (CSF) despite normal folate concentrations in plasma. The recent elucidation of cerebral folate transport mechanisms offers new therapeutic options to halt neurodegeneration. Compassionate use of folic or folinic acid in single KSS patients resulted in improvement of the clinical condition and brain white matter lesions. So far, no systematic clinical trial has been performed and no treatment protocol for folinic acid supplementation in KSS has been established. This clinical trial study investigates for the first time systematically the effect of oral and intravenous folinic acid administration on folate metabolites and proteins in CSF of KSS patients, on the clinical course and on the myelin pattern by MR imaging and spectroscopic techniques. The trial has the potential to establish a neuroprotective and neuroregenerative therapy for KSS that might be further applicable to related mitochondrial disorders and other cerebral folate deficiencies.

• DFG Programme: Clinical Trials
• Co-Investigator: Professor Dr. Ekkehard Wilichowski