Student Startup winner working on therapy of GM2 gangliosidoses
PhD student, Junior Research Associate of the Gene and Cell Technologies Lab Alisa Shaymardanova plans to conduct pilot testing on lab animals this year.
GM2 gangliosidoses are a group of three related genetic disorders that result from a deficiency of the enzyme beta-hexosaminidase. This enzyme catalyzes the biodegradation of fatty acid derivatives known as gangliosides. The diseases are better known by their individual names: Tay-Sachs disease, AV variant of GM2 gangliosidosis, and Sandhoff’s disease.
“GM2 gangliosidoses are a group of rare hereditary diseases that result from mutations in the genes for the lysosomal enzyme beta-hexosaminidase. The absence of this enzyme leads to severe neurodegeneration and neuroinflammation in patients. The frequency of the three diseases included in the group of GM2 gangliosidoses differs in different populations. Approximately the following frequency values are indicated in the literature: Tay-Sachs disease 1:3,500-100,000, Sandhoff’s disease 1:300,000, GM2 activator deficiency <1:300,000,” explains Shaymardanova.
She has been working on gene therapy for three years. At this time, there are no medications to treat gangliosidoses. The project first set off thanks to private investment. The developed gene preparation is a vector based on recombinant adeno-associated virus serotype 9 containing a genetic cassette encoding the genes for the enzyme missing in patients. The introduction of such a drug allows to deliver a healthy gene to the nervous system. After that, the patient’s nerve cells begin to synthesize the necessary enzyme. The vector is safe, non-immunogenic, non-toxic, and non-cancerogenic.
As a result of the project, the world’s first drug can be developed that will stop the progression of GM2 gangliosidoses, Shaymardanova emphasized. According to her, to date, the functionality of the genetic cassette used to create a gene preparation in cell cultures and small laboratory animals has been shown. After receiving these results, the design of the gene preparation was improved, a new vector based on adeno-associated virus serotype 9 was developed.
Active cooperation has been established with industrial partners who are interested in the sale of gene preparations for the treatment of rare human hereditary diseases. Moreover, drugs must pass preclinical and clinical trials before entering the market. Clinical trials of orphan drugs can take several years. At the same time, serious funding is required to conduct full-fledged preclinical studies. According to the interlocutor, 1 million rubles won as part of the Student Startup will be spent on the purchase of reagents and materials for the production and testing of the gene preparation on large laboratory animals.
So far, two Russian patents have been obtained.