New Treatment for Molybdenum Cofactor Deficiency Now Available

Molybdenum Cofactor Deficiency (MoCD) is an extremely rare genetic metabolic disorder, with only around 150 documented cases worldwide. The condition is primarily caused by mutations in multiple genes, with the majority of MoCD patients having type A, which is characterized by loss-of-function mutations in the MOCS1 gene responsible for coding the Molybdenum Cofactor Biosynthesis Protein 1 (MOSC1).

Without functional MOCS1, the body cannot produce the intermediate compound cyclic pyranopterin monophosphate (cPMP), leading to a blocked molybdenum cofactor (MoCo) metabolic pathway. This blockage results in a deficiency of functional sulfite oxidase, causing the accumulation of toxic sulfites in the brain.

The disease typically manifests in newborns, presenting symptoms such as persistent seizures, growth impairments, and other indications that may lead to rapid neurodegeneration.

In Germany, for the first time, a treatment option has been approved for MoCD patients with the introduction of Fosdenopterin (Nulibry® 9.5 mg powder for injection, TMC Pharma). This new drug is indicated for patients diagnosed with MoCD type A, requiring either a confirmed genetic diagnosis or a suspected diagnosis of this condition.

Nulibry serves as a substrate replacement therapy, containing Fosdenopterin, a synthetic form of cPMP. Once administered, it converts to molybdenum cofactor, which is essential for activating molybdenum-dependent enzymes, including sulfite oxidase, thereby reducing neurotoxic sulfite levels.

The orphan drug is administered intravenously once daily. For patients aged one year and older, the recommended dose is 0.9 mg per kg of body weight. For younger patients, the dosage is adjusted based on gestational age, and detailed guidelines for initial dosing and titration are included in the product information.

Animal studies have indicated a potential risk for phototoxicity associated with Fosdenopterin. Consequently, patients receiving this treatment and their caregivers must be advised to minimize exposure to direct sunlight and artificial UV light, and to take appropriate precautions. Vitamin D supplementation may also be considered as part of the treatment plan.