Amsterdam Molecular Therapeutics published data in the Journal of Clinical Endocrinology & Metabolism demonstrating that one-time administration of the gene therapy Glybera® (alipogene tiparvovec) in five patients markedly improved chylomicron metabolism 14 weeks after consuming a low-fat meal. That improved metabolism is reflected by a much reduced level of newly formed chylomicrons in the bloodstream, considered the cause of the acute and recurring bouts of pancreatitis seen in lipoprotein lipase deficiency subjects.
The American Society of Gene and Cell Therapy (ASGCT) has requested that the NIH Recombinant DNA Advisory Committee (RAC) no longer review protocols for gene therapy clinical trials, citing increased experience and familiarity with the field by FDA and institutional ethics and biosafety boards following more than 1,000 U.S. trials over the past 20 years. “The need to review individual protocols has diminished as the research community has acquired extensive safety data and the general public has become satisfied that these protocols have not led to modification of the human genome or to creation of novel transmissible pathogenic agents,” ASGCT president R. Jude Samulski, Ph.D. and president-elect Xandra O. Breakefield, Ph.D., wrote in a March 1 letter to Amy Patterson, M.D., director of NIH’s Office of Biotechnology Activities.
During a long-term follow-up of subjects in a Phase I study, researchers from University of California (UC) San Francisco, UC Berkeley, and Genzyme gave 10 patients with moderately advanced Parkinson disease either low or high doses of AAV2-hAADC (human aromatic L-amino acid decarboxylase) gene therapy. Results, published in the April 2012 issue of Human Gene Therapy, showed the elevated PET signal observed in the first 12 months—a significantly increased PET value compared to presurgery baseline—persisted over four years in both dose groups. However, the Unified Parkinson’s Disease Rating Scale in all patients off medication showed a marked decline in the first 12 months, followed by a slow deterioration in later years. Researchers said the data indicates stable transgene expression over four years after vector delivery and continued safety, but also shows need for more study, namely a controlled efficacy trial and the use of a higher vector dose. The challenge of developing effective gene therapy treatments for PD was also reinforced by news that another such developer, Neurologix, filed for protection from creditors under the U.S. Bankruptcy Code’s Chapter 7 liquidation of assets provision in U.S. Bankruptcy Court in Wilmington, DE. Neurologix’ pipeline includes gene therapies for depression, epilepsy, and Huntington disease.
Researchers from the U.S., Israel, and Italy have developed a gene therapy strategy that could feasibly treat both β-thalassemia and sickle cell disease, based on delivery of a lentiviral vector carrying both the human β-globin gene, and an ankyrin insulator to improve gene transcription and translation, and boost levels of β-globin production. Building on the success of prior gene therapy studies in mice, and the first evaluation of gene therapy in β-thalassemia patient, the Weill Cornell Medical College-led team developed a new lentiviral vector, designated AnkT9W, which carries both the human β-globin gene and the erythroid-specific ankyrin 5´ hypersensitive barrier insulator. Stefano Rivella, Ph.D., and colleagues reported on their study in PLoS One.
New This Year: Human Gene Therapy Methods
The field of gene therapy is rapidly evolving and holds great promise for its applications in treating human diseases. Human Gene Therapy launched Human Gene Therapy Methods to complement the flagship publication. HGT Methods answers the need for a central forum for nurturing, promoting, and advancing new technologies and methods that will ultimately pave the way for product development. The Editor in Chief is James M. Wilson, M.D., Ph.D.