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.
Franck Lemiale, PhD, Senior Director of Vaccines and Immunology for VIRxSYS just returned from Los Cabos, Mexico where he presented at HIV DART 2010: Frontiers in Drug Development for Antiretroviral Therapies. The presentation covered all the proprietary lentiviral vector technology utilized in the VRX1273 HIV Vaccine and summarized the preclinical vaccine work performed in non-human primate (NHP) studies. Although we have presented VRX1273 to world class scientific audiences several times before, this was the first time we have been invited to present to such a premier audience of HIV/AIDS clinicians. The presentation was very well received and the follow up panel discussion provoked positive interest. Several experts approached us with proposals to collaborate on such clinical eradication trials. The enthusiasm for our role as an important and unique approach to an HIV cure is very encouraging as we move forward with the development of VRX1273.
Today is World AIDS Day. Established in 1988 by the World Health Organization, World AIDS Day commemorates the theme of universal access and human rights. The organization World AIDS Campaign is primarily responsible for the observance. This year the day will focus on the Lights for Rights campaign with events taking place all over the world. Today is an opportunity to spread awareness and take action for universal access to HIV prevention, treatment, care and support. We hope that our work to develop less expensive and less toxic HIV therapies will eventually lead to a functional cure for HIV that is easily available to everyone around the world. Find out how you can take action for World AIDS Day.
Riku Rautsola, President and CEO of VIRxSYS, participated in a special session on HIV at the American Public Health Association (APHA) Annual Meeting & Exposition this week. The APHA Annual Meeting & Exposition is the principal congregation for public health professionals to learn about and share cutting edge research, exceptional practices, and innovative products and services. It is the largest and oldest gathering of public health professionals in the world, with more than 13,000 specialists from around the world. The goal of the APHA Annual Meeting & Exposition is to addresses current and emerging health science, policy, and practice issues in an effort to prevent disease and promote health. With over 30 million people living with HIV worldwide, there is an urgent need to decrease incidence and prevalence of the disease by reducing transmission and develop lower-cost treatments. In response, this year a special session explored factors related to HIV treatment issues, providing the opportunity to understand issues related to HIV development and research in the context of the epidemic today. Dr. Rautsola presented information on VRX1273, the therapeutic and preventative vaccine, being developed by VIRxSYS. VIRxSYS believes that VRX1273 vaccine has the potential to be a functional cure for HIV, with reduced cost and toxicity compared to existing treatments. VIRxSYS is honored to be invited to present at the APHA Annual Meeting.
This week we will be sharing results from a study of VRX1116, a simian analog for an investigational, lentiviral-based vaccine for HIV VRX1273, at the AIDS Vaccine 2010 conference in Atlanta, GA. This conference is focused on bringing together HIV opinion leaders. We are honored and exited to be sharing our research, which we feel has reached a milestone. AIDS Vaccine 2010 is being held September 28 – October 1, 2010 at the Omni Hotel in Atlanta, Georgia. The VRX1116 data will be presented as “Highly immunogenic lentiviral vaccine provides control of viral load, preservation of the CD4 compartment, and survival advantage post-SIV challenge” at 6:30pm Eastern Standard Time.
Today Dr. Jenice D’Costa, Senior Scientist at VIRxSYS, participated in the Maryland Stem Cell Research Symposium. The event featured research supported by the Maryland Stem Cell Research Fund (MSCRF) and federal agencies in the state of Maryland as well as presentations and poster sessions by researchers, such as VIRxSYS, who have been awarded MSCRF grants. This marks the first time in U.S. history in which both state and federal entities collaborated to address critical issues in stem cell research. VIRxSYS received a grant from the Maryland Stem Cell Research Commission (MSCRC) to develop safer methods for induced pluripotent stem cell (iPS) using the company’s proprietary spliceosome-mediated RNA trans-splicing (SMaRT™) and lentiviral gene delivery platform technologies. iPS cells have the ability to develop into different cell types in the body and have potential therapeutic applications for the regeneration of damaged organs or replacement of defective tissues with genetically corrected stem cells, giving these cells many potential clinical applications. If iPS cells are administered using gene delivery systems that integrate within the DNA of the cells, there is a possibility that they may be reactivated to express pluripotency factors inappropriately. The VIRxSYS lentiviral vector delivery system is thought to be safer because it is integration deficient and will result in only transient expression of these factors, which will eventually be lost as the cells are reprogrammed into pluripotent stem cells. The VIRxSYS SMaRT™ technology will link the expression of these ‘reprogramming” factors to genes which are turned on only at the relevant stage of cell differentiation, and then shut off once iPS are generated. The VIRxSYS technology is an elegant alternative to the current methods in practice to generate iPS cells using virus based delivery techniques without their potential downsides.
When one looks at the fight against HIV/AIDS in the third world, there have been very few victories. We were reminded this week about one significant accomplishment in those regions, that being the fight against Mother-to-Child transmission of HIV. The program Prevention of Mother-to-Child Transmission of HIV (PMTCT) provided nevirapine at no cost to infected mothers and newborn babies from 2000 to 2010 as a way to prevent HIV transmission. PMTCT is credited with saving four million babies from HIV infection. Please click here for the final report of the project. I am proud to say that Dr. Riku Rautsola, our President and CEO, was instrumental in launching the Mother-to-Child program when he was with Boehringer Ingleheim. He also co-founded and chaired “Accelerating Access,” which focused on providing low-cost HIV treatments in developing countries. Dr. Rautsola and our team here at VIRxSYS continue the search for breakthrough therapies for the treatment of HIV.
- Gary J. McGarrity, PhD – Executive Vice President of Scientific and Clinical Affairs
Therapeutic HIV vaccines were once considered to be a dead end. However, several recent research studies presented during a special session at the 2010 International AIDS Conference (IAC) show the renewed hope for therapeutic vaccines in the fight against HIV/ AIDS. An article in Nature also discussed the new developments in therapeutic HIV vaccines.
A typical vaccine, which does not yet exist for HIV, is designed to prevent infections, whereas a therapeutic vaccine treats infected people. Therapeutic HIV vaccines aim to boost damaged immune systems. Current HIV drug combination treatments have a high level of toxicity and often cause premature aging. Therapeutic vaccines have the potential to treat HIV without such side effects. Clinical trials on therapeutic HIV vaccines in the 1990’s were not successful and the line of research was marked as a failure. Currently several biotechnology companies are re-examining the potential of therapeutic vaccines for HIV with positive results.
The VIRxSYS Corporation is working to create a therapeutic HIV vaccine (VRX1273) using lentiviral vectors. This unique approach shows tremendous promise in treating those infected with HIV/ AIDS. CEO Riku Rautsola presented updated data from the Company’s HIV vaccine study during the National Association of People with AIDS (NAPWA) and The AIDS Institute’s Community Forum at International AIDS Conference 2010 in Vienna, Austria. VIRxSYS is excited to be a part of the active conversation on the potential of therapeutic HIV vaccines.
Significant strides utilizing gene therapy to create potentially effective HIV treatments continue to be made in our lab and others’. In addition to our work with Lexgenleucel-T (VRX496™) anti-HIV therapy, in which we modify autologous CD4 T cells to prevent HIV replication and is currently being tested in Phase II human clinical studies, we are seeing promising gene therapy reports out of other labs.
Nature Biotechnology has recently published a study conducted at UCLA in which stem cells, genetically modified with zinc finger nucleases to disrupt the viral co-receptor CCR5, were transplanted into humanized mice. After transplant, the mice were infected with HIV, as were control mice who received unmodified stem cells. The genetically modified cells multiplied into immune cells that successfully conferred HIV control. Mice that received the modified cells had higher human T cell counts and lower viral loads compared with animals that received unmodified cells. Although it will be several years before such research can be tested in human clinical trials, the success in humanized mice supports the potential for a successful gene therapy treatment for HIV. Clinical success of this type of approach will depend on several factors, including whether the HIV can mutate around this block as well as the specific tropism of HIV that a patient has. The study also provides further evidence that modifying just a fraction of the immune cells can potentially confer HIV resistance, much as we have observed in our Lexgenleucel-T studies to date.