The only way to avoid early death in Fabry's disease is named.

The only way to avoid damage to vital organs in Fabry's disease, as well as reduce the risk of severe complications and early death, is to start therapy early. This opinion was expressed by the American geneticist Robert J. Desnik, a pioneer in the development of drugs for the treatment of Fabry's disease. Professor and Chairman of the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai Hospital in New York spoke about the intricacies of diagnosing and combating this disease during a speech at the XI Congress of the Russian Society of Medical Geneticists, held in St. Petersburg in May.

Fabry's disease is a rare hereditary disease that causes deficiency of the enzyme alpha-galactosidase. It leads to the accumulation of lipids in cells and severe damage to various organs, including the heart and kidneys. In this case, the disease can manifest itself in various forms, depending on the degree of enzyme deficiency and the patient's gender. The classic phenotype of the disease manifests itself in childhood, usually at the age of two or three years. Like hemophilia, this is an X-linked disease, and boys suffer from it mainly: they suffer from burning pains, lack sweating, and a specific rash appears.

"Such boys are, in fact, bedridden at a fairly early age. (...) Further, with age, as a rule, the kidneys are affected. (...) In addition, by the age of 25, as a rule, heart damage develops in the form of hypertrophy of the left ventricle. And over time, changes in the myocardium lead to the development of a disease known as hypertrophic cardiomyopathy. Its characteristic feature is cardiac arrhythmia and atrial fibrillation, in particular. Atrial fibrillation itself, or atrial fibrillation, as it is also called, is a very common cause of strokes in such patients," said Desnik.

However, he stressed that it is kidney damage that most often leads to premature death. According to him, such patients rarely lived to be 40 years old before the introduction of enzyme replacement therapy. Desnik noted that there are also patients in whom the disease debuted in later adulthood. They have no classical manifestations of the disease, because of this they could not be diagnosed and were treated as cardiological or nephrological patients. Another group of patients who have difficulty detecting Fabry's disease are girls and women. They are either just carriers of a mutated gene, or their disease is in a milder form.

Thanks to his experiments, including sequencing and cloning the GLA gene, as well as creating a mouse model of the disease, Robert J. Desnik developed the world's first enzyme replacement therapy for Fabry's disease. The result of advanced research conducted in his laboratory was the creation of the drug agalsidase beta, which was registered by the FDA (US Food and Drug Administration) in 2003. The drug is the "gold standard" of Fabry disease therapy. Due to the mannose-6-phosphate residue, the enzyme penetrates into lysosomes and destroys lipids accumulated there due to the disease.

Other drugs were developed in parallel, but they were not registered by the FDA and are not used in the United States due to their lower effectiveness. This, in particular, concerns alpha-agalsidase, the lower efficiency of which is explained by the lower content of mannose-6-phosphate. In addition, unlike agalsidase beta, agalsidase alpha does not lead to complete clearance of the substrate from the kidneys. In Russia, there is a biosimilar of the drug agalsidase beta – Fabagal. The medicine is produced in the country in a full cycle, starting with the synthesis of the substance from the cell line. Robert J. Desnik highly appreciated this tool. In particular, the geneticist emphasized that it has similar characteristics: pharmacokinetics, dosage and glycosylation profile, and, accordingly, the same effectiveness.

"Since in this case we are talking about a biosimilar, this allows us to sell the drug, naturally, at a lower price than the original drug. In Russia, the price difference, as far as I know, is about 40% compared to its foreign counterpart. We compared all the physical characteristics and genetics of the drugs, and they are completely identical. And the dose is exactly the same. I hope that such a biosimilar can be used in other countries, which will save budget money and reduce costs. This is an important advantage of biosimilars," the scientist noted.

To date, 350 people have been diagnosed with Fabry's disease in Russia, and the number of patients with this diagnosis has increased 70-fold over the past 10 years, but a significant number of cases remain undiagnosed. According to Sergey Moiseev, Head of the Department of Internal, Occupational Diseases and Rheumatology at Sechenov University, Director of the Tareev Clinic, Corresponding Member of the Russian Academy of Sciences, the number of patients with Fabry's disease in the Russian Federation may exceed 5.8 thousand.

Moiseev noted that all modern diagnostic methods have been implemented and are currently in operation in Russia. If a child with Fabry's disease appears in the family, all relatives are also subject to examination. In addition, three foreign drugs as well as one domestic drug are available to patients.

"However, making a diagnosis still remains a difficult task. And in many cases, the correct diagnosis is made belatedly," the professor said in an interview with Rossiyskaya Gazeta.