Hunter syndrome: First steps of genomic edition applied in humans

The Hunter syndrome is an X-linked recessive disease, caused by a deficiency of iduronate-2-sulfatase, which normally cleaves a sulfate group from the glycosaminoglycans (GAGs), heparan and dermatan sulfate. A shortage of I2S leads to an accumulation of undegraded GAGs within the lysosomes of various organs and tissues, including the central nervous system. The abnormal deposition of GAGs alters the correct function of cells and tissues, resulting in severe damage and dysfunction of multiple organs and systems, leading into a broad spectrum of chronic and progressive clinical manifestations.

The estimated incidence of Hunter syndrome is between 0.69 and 1.18 per 100,000 live births and according to information published by a study in Portugal (Pinto et al., 2004), found that this syndrome is one of the most prevalent lysosomal storage disorders (LSDs) in the Portuguese population. However, this rare disorder is X-linked and it occurs almost exclusively in males. In addition, the age plays a major role: as patients age, they usually present severe manifestations. In the first months of life, the most common symptoms are respiratory problems, inguinal or umbilical hernia, short stature, and gingival hyperplasia. Patients also present an increased frequency of recurrent respiratory infections. Moreover, from a neurological perspective, most of them present psychomotor retardation, behavioral disturbances and neurological regression.

To help to reduce or retard the severe manifestations, there are only few treatments; but there is not a permanent solution since it is a genetic disease. That is why if we change what is wrong in the nucleotide sequence of the DNA, it is possible to correct those mistakes and avoid transmitting to the next generations.

Scientists of the UCSF Benioff Children’s Hospital are trying to correct those mistakes using a genomic edition approach. In which a patient with the name of Brian Madeoux, who has the Hunter syndrome, received a medicine containing thousand and millions of copies of a correcting gene joined to a genetic tool, capable of DNA modification. This tool named as a “Zinc Finger Nucleases”, which is the predecessor of CRISPR and its mechanism of action consists in cutting the place in the DNA structure that contains the gene responsible of the disorder and then inject a correcting gene. Moreover, the instructions of this complex codified in a virus, that was previously modified to go directly to the liver.

This would represent an important advantage for all the genetic disease because it represents the first steps into a possible permanent solution. As many other treatments, it could have serious effects in the patient’s health. Since it is a modification in the DNA, it could have serious effects for life.

These types of new strategies are under research every day and here in Althian we like to be always aware of the latest news. Give us a call and we will be more than happy to assist you if you want to run a complex clinical trial.