The drug fosdenopterin/rcPMP considerably improves the chances of survival and developmental progress in infants with molybdenum cofactor deficiency (MoCD type A), a rare and life-threatening genetic condition causing an inborn error in metabolism. This was shown in a clinical study recently published by an international research team led by Professor Dr. Günter Schwarz from the Institute of Biochemistry at the University of Cologne.

MoCD type A is a very rare disease. It affects around one in 200,000 to 500,000 newborns and is caused by genetic mutations that lead to the loss of the molybdenum cofactor (Moco). Ultimately, several enzymes in the newborn’s metabolism are affected and are no longer able to function, thus causing very fast progressing and irreversible brain damage to affected infants, with childhood death as a typical outcome.

The clinical study has now shown that early treatment with fosdenopterin in the first days of life significantly reduces the risk of early death and promotes healthy brain development. The study was published under the title “Treatment of molybdenum cofactor deficiency (MoCD) Type A with cyclic pyranopterin monophosphate (cPMP)” in the Journal of Inherited Metabolic Disease.

Without treatment, MoCD type A results in severe impairments such as seizures and severe developmental and movement disorders, and often leads to early death within the first few months of life. Until recently, the only treatments available for patients with MoCD were symptomatic. They therefore targeted the symptoms and not the actual cause of the disease.

The present study now shows that treatment with fosdenopterin/rcPMP combats the underlying cause of MoCD type A by restoring the missing molecule cPMP. The researchers found that early administration of this drug can not only prolong life, but also promote important developmental milestones such as sitting, walking and eating behavior. The infants treated in the study showed significant improvements compared to untreated patients, with many achieving development equivalent to that of healthy infants.

Due to the rarity of the disease, it is difficult to conduct a large-scale, controlled clinical trial on the efficacy of the drug. The research group was able to demonstrate the drug’s effectiveness in a mouse model back in 2004.

The first patients have been receiving treatment with the active substance fosdenopterin/rcPMP since 2008. The current publication therefore summarizes the results of three long-term studies that tracked the development of 14 treated patients compared to 36 untreated patients in their first months of life.

“The results show that fosdenopterin/rcPMP can significantly improve the prognosis of infants with MoCD type A,” says Professor Dr. Schwarz, first author of the study. “Our results emphasize the importance of research into rare metabolic diseases, which allows us to lay the foundations for new treatment options and establish better prospects for patients.”