The Food and Drug Administration (FDA) has given the go-ahead for a Phase 1 clinical trial of a gene therapy treatment that has the potential to cure human immunodeficiency virus (HIV) in patients. The US biotechnology firm American Gene Technologies (AGT) hope the single-dose therapy, called AGT103-T, will help to rid HIV/AIDS in the nearly 38 million people currently infected with the disease globally.
It should be noted, however, that some critics have asked the company to "tone it down," saying that although their method holds promise, clinical trials routinely fail during this phase.
The therapy, designed by AGT with the National Institute of Allergy and Infectious Disease (NIAID), will begin enrollment for the clinical trial in September and hope to have initial data to report by the end of the year.
"This is momentous news that we have FDA approval to launch Phase 1 and conduct our first human trials. We are beyond excited to reach this milestone. This brings us closer to our goal of transforming lives with genetic medicines,” said Chief Science Officer David Pauza in a statement. “Based on our successful commercial-scale product manufacturing runs and features of the product observed in our labs, this therapy has a high potential to be effective.”
Gene therapy for HIV has shown great promise in recent years, but so far attempts to eliminate the disease have been unsuccessful. The AGT103-T drug therapy aims to protect the patient’s immune system from HIV-related depletion of white blood cells. These immune cells, called CD4 T cells, usually signal other white blood cells to destroy invading pathogens and are instrumental in protecting against diseases both mild and severe.
In HIV infections, T cell counts are gradually lowered to the point that the immune system can no longer protect against even the simplest opportunistic pathogen, from Salmonella or thrush infections. Once the T cell count is sufficiently lowered or the patient has acquired an opportunistic infection, the patient is diagnosed with acquired immunodeficiency syndrome (AIDS) and their life expectancy is typically reduced to just three years.
To prevent this, AGT are creating a virus "delivery vehicle" (lentivirus vector) to insert protective genes into T cells, creating versions of the patient’s own immune cells that can resist HIV infection. This way, instead of simply replenishing cells that are lost to HIV, the therapy can produce cells that cannot be invaded by the virus, halting the production of HIV and preventing depletion of the immune system. Once these cells are produced after an 11-day process, they are delivered back into the body.
In a study in Molecular Therapy in June, human T cells treated with AGT103-T showed the ability to defend against HIV particles and HIV-infected human cells. Should the presence of these cells be sufficient, the virus would be unable to replicate enough within the body for infection to continue and the affected person would be cured.
This new method is fast, cost-efficient, and reliable, and AGT are hopeful it could impact millions of people if successful. The researchers behind the therapy are calling it the ‘Achilles heel’ of HIV and a testament to the advances being made in medicine.
However, it is important not to get carried away with new treatments. This trial is only the first step in a long process of understanding the safety, efficacy, and applicability of the drug, and many possible treatments fall short at the coming hurdles. Speaking in an article posted to Science Translational Medicine, Derek Lowe highlights the importance of caution when it comes to medical advances and potential new cures. Lowe believes pharmaceutical companies, including AGT, are complicit in the hyping-up of ideas as cures without the necessary data to substantiate them.
"There are a lot of things that can go wrong with gene therapy, and there are a lot of things that we don’t yet understand about its applications," Lowe said. "...using 'cure' for what are actually just interesting ideas in preclinical development is just not right."