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Hongwei Zhang

Hongwei Zhang, Ph.D., is assistant professor in the Department of Pharmaceutical Sciences at South Dakota State University.

After a decade of disappointment and a number of major setbacks, gene therapy may be achieving a great renaissance. Gly­bera, a recombinant adeno-associated virus (rAAV)-based treatment for patients who cannot break down fats due to the lack of a critical enzyme, lipoprotein lipase (LPL), was backed by the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use. With regulatory approval by the European Commission anticipated in the next days, the persistent efforts in producing better gene delivery vectors and collecting clinical data to demonstrate the therapeutic efficacy and safety, especially in rare monogenic inherited disorders, paid off.

Glybera, which is administered by several injections into the leg muscles in a single treatment, uses an rAAV to deliver the correct copy of the aberrant gene to produce LPL. Two amazing advantages of this technology are that the delivered gene: 1) persists in the patients’ cells for very long time, thus producing the enzyme long term, and 2) has an extremely low chance to integrate into the host genome, thus minimizing insertional mutagenesis.

If Glybera, developed by a Dutch company called uniQure, eventually obtains market approval, it will be the fourth commercial gene therapy product approved in the world, following Gendicine (China, 2003), Oncorine (China, 2005), and Neovasculogen (Russia, 2011). It will not only provide a valuable treatment for the patients who are suffering from LPL deficiency but also provide a major boost to the gene therapy community overall. In fact, the investment to gene therapies has been increasing in the past several years due to the encouraging clinical data in different gene therapy trials. It is expected that more gene therapy products targeting other monogenic inherited disorders or even cancer will be approved in the next few years, given the big candidate-pool of gene therapy products in human clinical trials.

Significant work still needs to be done to make this genetic drug beneficial to patients. Since the price of Glybera is expected to be over 1.25 million euros per patient, getting Glybera covered by medical insurance appears to be the best way for most patients to afford it. It is also very important to follow the patients who have received this drug to monitor its safety and efficacy.

The Europe Union is now sitting at the forefront of gene therapy with China and Russia. In the United States, the death of Jesse Gelsinger in 1999 resulted in a grinding halt on gene therapy. Since then, many technical barriers and safety concerns in gene therapy have been addressed. It is anticipated that gene therapy is going to cross the finish line in the United States in the next few years. One of the lead candidates for approval is the rAAV-based treatment for Leber’s congenital amaurosis, an inherited eye disease. uniQure expects to file with the Food and Drug Administration this year.