The US Food and Drug Administration (FDA) has approved Wellcovorin (leucovorin calcium) tablets for the treatment of adult and pediatric patients with cerebral folate deficiency (CFD) with confirmed variants in the folate receptor 1 gene (CFD-FOLR1). The drug was previously approved as part of a chemotherapy regimen that involved methotrexate to limit the latter’s toxicity.
CFD is a rare neurologic condition resulting from brain-specific folate deficiency early in life. Onset is apparent in late infancy with severe developmental regression, movement disturbances, epilepsy, and leukodystrophy. Cerebral folate deficiency is typically caused by deficiency of vitamin B folate in the brain due to low levels of 5-methyltetrahydrofolate (5MTHF) in the cerebrospinal fluid (CSF) caused by a disruption in the function of the folate receptor alpha (FRA). However, a rare mutation in the FOLR1 gene can result in an autosomal recessive genetic condition which disrupts FRA function.
Low levels of folate have been observed in some individuals with autism but the current evidence does not indicate CFD is a genetic form of autism, nor is leucovorin necessarily a viable treatment option for autism, as suggested by some officials. This continues to be a controversial topic and our readers are encouraged to research the topic, including a recent editorial published in the New England Journal of Medicine.
The approval of leucovorin to treat patients with CFD is largely based on a systematic review of published literature analyzing leucovorin in 46 patients with CFD-FOLR1. A total of 27 of these patients were treated with oral leucovorin. Twenty-four of the 27 patients reported clinical improvements in various neurological symptoms with oral leucovorin. CSF 5MTHF levels were also analyzed and an increase in these levels was observed in all 27 patients.
The most common adverse reactions reported with leucovorin were pruritus, rash, urticaria, dyspnea, hypersensitivity reactions, rigors, and temperature change.
For more information, visit www.fda.gov
To learn more about rare neurological conditions, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/
