In vivo Genome Editing – First study patient with mucopolysaccharidosis type II receives novel gene therapy
There have been several approaches to a functioning gene therapy since the early days of research. Previous approaches have used mechanisms that are also used in cell culture research to bring certain genes into cells, e.g. to introduce them into the genome on behalf of viruses or to infiltrate specific DNA that is read directly in the cell. The new therapeutic approach, which is now being tested in an international study, was developed by the company Sangamo Therapeutics. With this technology it is possible to detect certain DNA sections in the human genome via so-called Zinc Finger proteins and thus to modify specific target genes. The therapy aims to treat mucopolysaccharidosis type II, a genetic disorder that causes severe multi-organ damage and for which no causal therapy exists so far. The disease is triggered by the defect of an enzyme gene. In the treatment, a restriction site is inserted into the gene region of the albumin, the most produced protein by the liver, and the cell's natural DNA repair mechanisms are used to firmly integrate the defective gene into the albumin gene region at this restriction site. Since albumin is produced to a high degree, the specific addressing of this gene locus is expected to result in a higher production of the defective enzyme and thus a higher success of the therapy than with previous gene therapy approaches.
So far, mucopolysaccharidosis type II is treated with a so-called enzyme replacement therapy, in which the defective enzyme is administered to the patients by infusion. However, after infusion, enzyme levels rapidly decline and the consequences of the disease for e.g. the nervous system, the heart or the respiratory system can be delayed but not averted.
The novel gene therapy from Sangamo Therapeutics has the name SB-913 and is currently being evaluated in the Phase 1/2 CHAMPIONS study.
SKC has significant experience in strategically supporting the market access of gene therapy products.
BY Prof. Matthias P. Schönermark, M.D., Ph.D., Founder and Managing Director, SKC Beratungsgesellschaft mbH
Further details and the publication of the results from the preclinical research can be read here:
UCSF Benioff Children’s Hospital Oakland Has First Patient in Landmark Clinical Trial Evaluating "In Vivo" Genome Editing for Rare Genetic Disorder
Socialstyrelsen - hunter syndrome
Clinicaltrials.gov - Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-913 in Subjects With MPS II
Sangamo therapeutics
NCBI - In vivo genome editing of the albumin locus as a platform for protein replacement therapy