HIV/AIDS - A Global Problem
An estimated 39 million people worldwide are infected with HIV (2006 UNAIDS Report). In the United States, more people than ever are living with HIV, an estimated 1.2 million in 2005 (2006 UNAIDS Report). Changes in incidence along with rising AIDS mortality have caused global HIV prevalence to level off. However, the number of people living with HIV has continued to rise due to population growth and, more recently, the life-prolonging effects of antiretroviral therapy (2006 UNAIDS Report).
Limitations of Current Drug Therapies for HIV/AIDS
Highly-active Antiretroviral Therapy (HAART), or triple cocktail drug therapy as it is also known, was once believed to have great promise in effectively combating the AIDS virus. Unfortunately, HAART has not proven to be a cure for AIDS because the virus is estimated to have the ability to remain latent for a period of 50 years or more (Siliciano et al. 2004).
Additionally, there are concerns regarding adverse effects associated with long-term use of HAART. Specifically, a variety of metabolic disorders including HIV-associated lipodystrophy, central adiposity, dyslipidaemia, hyperlipidaemia, hyperglycemia and insulin resistance have been reported as resulting from HAART (Vigouroux et al., 1999; Behrens et al., 2000; Powderly, 2002). These reactions, which occur in up to 30% of patients for each drug in a treatment regimen of three drugs, combined with complex and cumbersome dosing regimes, can have an adverse impact on patient adherence to drug regimens (Lucas et al., 1999; Max and Sherer, 2000). Considering the percentage of adverse events when taking three drugs together, it is evident that management of HIV infection with HAART is difficult for a large proportion of patients.
Lack of adherence to antiretroviral regimens leads to resistant HIV strains. In fact, HIV resistance to drug therapy is increasing and with research indicating that more than 20% of newly-transmitted HIV is resistant to any drugs available today (Rapid Report for the 2004 Resistance Workshop). It has become apparent that HAART therapy is not the solution for controlling the AIDS epidemic long-term, even in developed countries like the United States.
VIRxSYS's Gene Therapy Solution for HIV/AIDS
Because of the limitations of HAART, alternative therapies for HIV are needed. The Company's novel technology provides biological control of HIV infection by turning the HIV virus against itself using an HIV lentiviral vector, VRX496. This HIV vector contains an antisense that inhibits HIV replication. Short antisense, such as ribozymes or RNAi, may be more likely to result in HIV strains that are resistant to the therapy. However, VRX496 has a long antisense, which debilitates HIV's ability to resist the treatment -- a major problem with current drug treatments.
VRX496 lies inactive waiting for HIV to attack. Replication of HIV within a T cell triggers the replication of VRX496, which then binds to and destroys the HIV.
Click here to see an animation of how VRX496 works.
Preclinical and clinical evaluation to date, has shown VRX496 to (i) efficiently deliver therapeutic payloads, (ii) inhibit HIV replication, and (iii) be a safe and tolerable therapy. Such inhibition of HIV replication in HIV-infected patients could indefinitely postpone HIV disease progression to AIDS. Currently, VIRxSYS has the only lentiviral vector used in human clinical trials approved by the U.S. Food and Drug Administration.
VRX496, a CD4 T cell treatment against HIV, is the first application of VIRxSYS’s proprietary lentiviral vector platform. The backbone of VRX496 is our proprietary lentiviral vector an efficient gene-delivery vehicle. VIRxSYS then equips the vector with a long antisense sequence against the HIV envelope protein to create VRX496. VRX496 is transduced (inserted) into a patient’s own CD4 T cells to block HIV replication. Researchers believe this can enable the immune response against HIV and protect or restore normal immune function against other infections.
VIRxSYS’s first therapy tested in clinical trials is VRX496, an anti-HIV gene therapy (immunotherapy). The following graphic illustrates the steps involved in the ex-vivo cell processing of the patient's cells from a patient and manufacturing perspective.
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Click the image to enlarge.
VIRxSYS uses a state of the art, autologous process by which CD4 T cells are removed from a patient and treated (genetically modified) with VRX496. These genetically modified cells are then expanded to provide many multiples of the modified cells, which are then reinfused into the patient. Phase I and Phase II clinical trials to date, have shown that this process is safe and tolerable for the trial participants.
"VIRxSYS is committed to developing gene therapy technologies to treat a variety of serious human diseases. The first application of this technology is to treat HIV/AIDS."
Riku Rautsola, VIRxSYS CEO