The role of transferrin receptors in crossing the blood-brain barrier in the treatment of mucopolysaccharidosis

Background. Currently, in Russia, intravenous enzyme replacement therapy is used for the treatment of mucopolysaccharidosis type II. In recent months, enzyme replacement therapy administered via the cerebral ventricles (intracerebroventricular administration) has become available. The main drawback of this therapy is its inability to cross the blood-brain barrier. This means that available medications can target either the somatic manifestations of the disease or the neurological ones. For effective therapy aimed at alleviating all symptoms of the disease, it is necessary to administer two enzyme replacement therapies: intravenously, to address somatic symptoms, and intracerebroventricularly, to alleviate neurological manifestations of the disease.

Objective. This article is dedicated to new approaches in the treatment of mucopolysaccharidosis type II with a next-generation drug capable of crossing the blood-brain barrier. Two types of receptors are utilized for the passage of recombinant idursulfase through the blood-brain barrier: transferrin receptors and insulin receptors. Two drugs have been registered worldwide, each targeting a specific type of receptor. Materials and Methods. This article analyzes literary sources describing the mechanism by which drug molecules overcome the blood-brain barrier via transferrin receptors, as well as evaluates the impact of pabinafusp alpha on the neurological and somatic status of patients with mucopolysaccharidosis type II.

Conclusions. Pabinafusp alpha represents an innovative approach to the treatment of Hunter syndrome, providing the ability to cross the blood-brain barrier. This opens new horizons for therapy, allowing a single drug to comprehensively address both somatic and neurological manifestations of the disease. Studies show that pabinafusp alpha can improve neurological symptoms and the quality of life for patients and their families. Thus, this drug demonstrates promising results and may become the treatment of choice for patients with mucopolysaccharidosis type II.

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