The development of gene therapy, a method of correcting defective genes that cause disease, has been a long and difficult road for scientific researchers. “The Second Coming of Gene Therapy” in Discover Magazine provides an in-depth look at the history of gene and cell therapy and its renewed promise for the treatment of a wide range of diseases. From the 1980’s through the 1990’s, the scientific community’s hope for gene therapy was met with eminent disappointment. However, advances in recent years have revitalized the field, which now shows tremendous potential for developing treatments for serious diseases.
Recently, gene and cell therapy reached a milestone with the first study to show benefit to patients with a neurodegenerative condition. The results of the double-blind clinical trial conducted by the Department of Neurological Surgery at Weill Cornell Medical College in New York were reported in The Lancet Neurology. According to Nature, the experimental gene-therapy treatment for Parkinson’s disease, which symptoms include tremors, slowness, and cognitive dysfunction, eased the movement problems of a small number of patients and raised no major safety concerns. According to MSNBC, the study represents a positive step for gene and cell therapy, the affect was small and will need to be confirmed by a larger trial.
VIRxSYS is encouraged by the success of our peers as we work diligently to develop gene and cell therapies for serious diseases, such as HIV and cardiovascular diseases.
Tessio Rebello, our Vice President of Clinical Affairs, just got back from the 18th Conference on Retroviruses and Opportunistic Infections (CROI) in Boston, MA. Although this year, VIRxSYS chose not to do a formal presentation of data, our attendance allowed us the opportunity to take meetings with several key thought leaders where we received praise for our research and forward-looking plans. We were delighted to find a reinvigorated interest in cell and gene therapies at the conference, demonstrating a shared vision among the HIV research community for an effective therapeutic HIV vaccine.
One presentation worthy of discussion came from Sangamo Biosciences Inc. on preliminary clinical data from its Phase 1 trial for autologous infusion of CD4 cells that have undergone zinc finger nuclease mediated CCR5 disruption will confer resistance to R5 tropic virus. The study attempts to replicate the results seen in the “Berlin Patient” who received a stem cell transplant to treat a severe case of leukemia with a donor who had a CCR5 delta-32 mutation, which prevents CD4 cells from developing a receptor called CCR5 on their surfaces, which in turn confers HIV resistance. The stem cell transplant in the Berlin Patient was successful, and nearly three and a half years later the patient remains without evidence of HIV in the circulation without the use of antiretroviral therapy. Many clinicians recognize that the “Berlin Patient” represents a success story as a “functional cure” for HIV.
VIRxSYS applauds Sangamo for its efforts to advance the progress toward an effective therapeutic HIV vaccine. However, it is premature to declare success of Sangamo’s small, early-stage study of an experimental therapy on only a handful of patients. Jay Lalezari, who presented the data at CROI, acknowledged that the engraftment seen in the Sangamo trial was far less than that seen in the “Berlin Patient.” The CCR5 disrupted cells accounted for one to six percent of the peripheral blood in five of the six patients. For complete resistance to HIV infection, one would need 100% of CD4 cells to be CCR5 disrupted, as seen in the “Berlin Patient.”
We believe that the unique approach of VRX1273 continues to show the most promise for durable suppression of viral load in infected subjects plus possible reduction of latent viral reservoirs, thus effecting a potential “functional cure” for HIV. Our preclinical nonhuman studies indicate the vaccine’s ability to fully control and suppress viral replication for as long as one and a half years post-challenge with a highly pathogenic simian immunodeficiency virus (SIV) and maintenance of CD4 counts with respect to pre-challenge baseline values. The simian version of VIRxSYS’vaccine was safely and repeatedly administered and proved to be highly immunogenic with sustained immune responses. We are confident VRX1273 will continue to demonstrate positive results as we move into human studies and will lead to a less-expensive, non-toxic treatment for HIV positive individuals.