Doctors Say They May Be Able to Destroy HIV; AIDS Cure?

[Einhander Sn0m4n]

Hooray for Houston, Texas!

Houston doctors say they may have found a way to destroy HIV

01:20 AM CDT on Wednesday, July 30, 2008

By LEE MCGUIRE
KVUE News

HOUSTON -- There is real hope that what’s happening in a Houston lab might lead to a cure for HIV.

AP

“We have found an innovative way to kill the virus by finding this small region of HIV that is unchangeable,” Dr. Sudhir Paul of the University of Texas Medical School at Houston said.

Dr. Paul and Dr. Miguel Escobar aren’t talking about just suppressing HIV – they’re talking about destroying it permanently by arming the immune system with a new weapon lab tests have shown to be effective.

Ford Stuart has been HIV positive for 15 years. He’s on a powerful drug cocktail that keeps the disease in check.

“I’m on four different medications. Three of them are brand new, and it’s the first time that I’ve ever been non-detectible,” Stuart said. “I’m down to about – just for the HIV – about nine pills per day, five in the morning and four at night.”

But Stuart knows HIV mutates, and eventually it will learn how to outsmart his medications.

“The virus is truly complex and has many tricks up its sleeve,” Paul said.

But Dr. Paul thinks he’s cracked a code.

“We’ve discovered the weak spot of HIV,” he said.

Paul and his team have zeroed in on a section of a key protein in HIV’s structure that does not mutate.

“The virus needs at least one constant region, and that is the essence of calling it the Achilles heel,” Paul said.

That Achilles heel is the doctors’ way in. They take advantage of it with something called an abzyme.

It’s naturally produced by people, like lupus patients. When they applied that abzyme to the HIV virus, it permanently disarmed it.

“What we already have in our hand are the abzymes that we could be infusing into the human subjects with HIV infection, essentially to move the virus,” Paul said.

Basically, their idea could be used to control the disease for people who already have it and prevent infection for those at risk.

The theory has held up in lab and animal testing. The next step is human trials.

Meanwhile, every day in Houston, three people are diagnosed with HIV.

The doctors still need funding to launch human trials. In the world of HIV research, that’s often where things fall apart.

“Clinical trials are very expensive,” Paul said.

“That is the worry of the researcher. This is what nightmares are made of – that after 30 years of work, you find it doesn’t work,” Paul said.

But so far, it is working.

“This is the holy grail of HIV research, to develop a preventative vaccine,” Paul said.

“If we can get the viral loads down to a manageable level, that will preclude the need for these conventional drugs,” Escobar said.

Still, even if everything goes well, it’s at least five years before the research could help people with HIV.

The doctors know people like Ford Stuart are waiting.

“There are so many people struggling with the disease because it affects not only your body, but also your psyche, how you perceive yourself,” he said.

If nothing else, the research is promising for the tens of millions waiting for a cure.

And now a more technical article from Physorg:

UT pathologists believe they have pinpointed Achilles heel of HIV
Medicine & Health / HIV & AIDS
Human Immunodeficiency Virus (HIV) researchers at The University of Texas Medical School at Houston believe they have uncovered the Achilles heel in the armor of the virus that continues to kill millions.

The weak spot is hidden in the HIV envelope protein gp120. This protein is essential for HIV attachment to host cells, which initiate infection and eventually lead to Acquired Immunodeficiency Syndrome or AIDS. Normally the body's immune defenses can ward off viruses by making proteins called antibodies that bind the virus. However, HIV is a constantly changing and mutating virus, and the antibodies produced after infection do not control disease progression to AIDS. For the same reason, no HIV preventative vaccine that stimulates production of protective antibodies is available.

The Achilles heel, a tiny stretch of amino acids numbered 421-433 on gp120, is now under study as a target for therapeutic intervention. Sudhir Paul, Ph.D., pathology professor in the UT Medical School, said, "Unlike the changeable regions of its envelope, HIV needs at least one region that must remain constant to attach to cells. If this region changes, HIV cannot infect cells. Equally important, HIV does not want this constant region to provoke the body's defense system. So, HIV uses the same constant cellular attachment site to silence B lymphocytes - the antibody producing cells. The result is that the body is fooled into making abundant antibodies to the changeable regions of HIV but not to its cellular attachment site. Immunologists call such regions superantigens. HIV's cleverness is unmatched. No other virus uses this trick to evade the body's defenses."

Paul is the senior author on a paper about this theory in a June issue of the journal Autoimmunity Reviews. Additional data supporting the theory are to be presented at the XVII International AIDS Conference Aug. 3-8 in Mexico City in two studies titled "Survivors of HIV infection produce potent, broadly neutralizing IgAs directed to the superantigenic region of the gp120 CD4 binding site" and "Prospective clinical utility and evolutionary implication of broadly neutralizing antibody fragments to HIV gp120 superantigenic epitope."

First reported in the early 1980s, HIV has spread across the world, particularly in developing countries. In 2007, 33 million people were living with AIDS, according to a report by the World Health Organization and the United Nations.

Paul's group has engineered antibodies with enzymatic activity, also known as abzymes, which can attack the Achilles heel of the virus in a precise way. "The abzymes recognize essentially all of the diverse HIV forms found across the world. This solves the problem of HIV changeability. The next step is to confirm our theory in human clinical trials," Paul said.

Unlike regular antibodies, abzymes degrade the virus permanently. A single abzyme molecule inactivates thousands of virus particles. Regular antibodies inactivate only one virus particle, and their anti-viral HIV effect is weaker.

"The work of Dr. Paul's group is highly innovative. They have identified antibodies that, instead of passively binding to the target molecule, are able to fragment it and destroy its function. Their recent work indicates that naturally occurring catalytic antibodies, particularly those of the IgA subtype, may be useful in the treatment and prevention of HIV infection," said Steven J. Norris, Ph.D., holder of the Robert Greer Professorship in the Biomedical Sciences and vice chair for research in the Department of Pathology and Laboratory Medicine at the UT Medical School at Houston.

The abzymes are derived from HIV negative people with the autoimmune disease lupus and a small number of HIV positive people who do not require treatment and do not get AIDS. Stephanie Planque, lead author and UT Medical School at Houston graduate student, said, "We discovered that disturbed immunological events in lupus patients can generate abzymes to the Achilles heel of HIV. The human genome has accumulated over millions of years of evolution a lot of viral fragments called endogenous retroviral sequences. These endogenous retroviral sequences are overproduced in people with lupus, and an immune response to such a sequence that resembles the Achilles heel can explain the production of abzymes in lupus. A small minority of HIV positive people also start producing the abzymes after decades of the infection. The immune system in some people can cope with HIV after all."

Carl Hanson, Ph.D., who heads the Retrovirus Diagnostic Section of the Viral and Rickettsial Disease Laboratory of the California Department of Public Health, has shown that the abzymes neutralize infection of human blood cells by diverse strains of HIV from various parts of the world. Human blood cells are the only cells that HIV infects.

"This is an entirely new finding. It is a novel antibody that appears to be very effective in killing the HIV virus. The main question now is if this can be applied to developing vaccine and possibly used as a microbicide to prevent sexual transmission," said David C. Montefiori, Ph.D., director of the Laboratory for AIDS Vaccine Research & Development at Duke University Medical Center. The abzymes are now under development for HIV immunotherapy by infusion into blood. They could also be used to guard against sexual HIV transmission as topical vaginal or rectal formulations.

"HIV is an international priority because we have no defense against it," Paul said. "Left unchecked, it will likely evolve into even more virulent forms. We have learned a lot from this research about how to induce the production of the protective abzymes on demand. This is the Holy Grail of HIV research -- development of a preventative HIV vaccine."

Source: University of Texas Health Science Center at Houston

Five years and we may be looking at a cure for AIDS. This is fucking wonderful!

[Ender]

Pretty sure we first heard about this a few years ago, and that it would specifically target and cure only a few strains of HIV and AIDs. Still, this means progress is being made.

[Cos Dashit]

Small steps are better than none.

[Einhander Sn0m4n]

And then there's this.

Researchers Halt Spread Of HIV With RNAi In Animal Model

ScienceDaily (Aug. 8, 2008) — Hopes languished last September when a promising candidate HIV vaccine failed to work. Despite this setback, many researchers still believe immunization is possible, and a new study suggests they're correct—at least at the cellular level.
See also:

Working in mice infected with HIV, a team used a method called RNA interference to knock down three genes in T cells, protecting them from the virus. This method seemed to prevent HIV from jumping between cells in the mice.

"For the first time, we've used RNAi to dramatically suppress HIV infection in an organism," says corresponding author Premlata Shankar, who conducted the work while she was a junior investigator at the Harvard Medical School-affiliated Immune Disease Institute and an assistant professor at Harvard Medical School. Shankar is now a professor at Texas Tech University Health Sciences Center in El Paso.

Although labs must verify the findings in other animal models before attempting clinical trials, this method—published online Aug. 7 in Cell — may eventually supplement or replace the harsh drug cocktails currently prescribed to patients with HIV, reducing the side effects of treatment.

When the Nobel Prize in Physiology or Medicine was awarded in 2006 for the discovery of RNAi, the judges speculated that it might "lead to novel therapies in the future." Researchers hoped to flood specific cells in patients with short interfering RNAs (siRNAs), molecules that silence genes by disrupting the protein templates they produce. But scientists weren't sure how to deliver the siRNAs exclusively into relevant cell types within an organism.

In collaboration with Sang-Kyung Lee of Hanyang University, Shankar's lab overcame this obstacle, delivering siRNAs directly into T cells, which are targeted by HIV. The team used an apparatus analogous to a truck equipped with GPS and a trailer hitch to haul the siRNAs to their destination. The truck—in this case, a single-chain antibody developed by Georg Fey of the University of Erlangen in Germany—homed to a protein found exclusively on the surface of T cells. The trailer hitch—an oligo-9-arginine—pulled siRNAs along for the ride.

This new antibody delivery vehicle lends itself to mass production in a dish. The team built thousands of these carriers for use in experiments, loading them with siRNAs targeting three key genes. One encodes a human protein called CCR5, which dots the surface of T cells and allows HIV to gain entry. The others encode proteins produced by the virus within cells upon infection.

Harvard Medical School postdoctoral researcher and first author Priti Kumar mixed the siRNAs with the antibody carriers and injected them into the veins of mice that harbor human T cells rather than their own. These mice serve as an animal model of HIV. After being infected with the virus, the mice mirror progression of the disease in humans.

Developed by study co-authors Leonard Shultz of the Jackson Laboratory and Dale Greiner of the University of Massachusetts, these mice lack their own immune systems, so they tolerate tissue from other species. The team injected the mice with human blood stem cells, which divided time and again, building a human immune system in their hosts. When infected with HIV, the synthetic immune system seemed to respond as it would in humans, since T cell levels followed the same pattern in both species.

Kumar's siRNAs halted T cell destruction in the mice, essentially stopping the virus in its tracks.

"Both prophylactic and therapeutic regimens proved successful," said Kumar. "Apparently, the siRNAs kept HIV from entering most T cells and kept it from replicating when it managed to slip inside."

Kumar and Shankar caution that labs need to confirm the findings in other animals, tweak the dosage, and tinker with the siRNA delivery vehicle before attempting clinical trials. In addition, the molecules degrade with time, so periodic shots may be necessary to maintain cellular immunity, precluding large-scale vaccination.

"I'm not saying we've developed tomorrow's therapy, but this is a major step forward," says Shankar. "We've used a small animal model for HIV and proven that RNAi works in that model."

John Rossi, a pioneer in RNA-based therapeutics who was not part of the study, hopes labs will use the new animal model to compare the side effects of potential and existing therapeutic regimens.

"The number one problem with the current antiretroviral drug regimens is toxicity," says Rossi, a professor at the Beckman Research Institute of the City of Hope. He wonders if siRNAs will eventually enable doctors to lower the doses of existing drugs in patients. Perhaps siRNAs will one day supplement or replace harsh antiretrovirals.

"Overall, I see this work as an exciting proof of principle," says Rossi. "This is a strategy that can be developed for clinical applications in humans."

This research is supported by the National Institutes of Health, the Korea Ministry of Education and Science Technology, and the Center for AIDS Research at Harvard.

Journal reference:

1. Kumar et al. T Cell-Specific siRNA Delivery Suppresses HIV-1 Infection in Humanized Mice. Cell, Online Aug. 7, 2008 DOI: 10.1016/j.cell.2008.06.034

[Admiral Valdemar]

In five years anything can happen. We could've cured any number of diseases with various drugs and therapies when we finally found a suitable mechanism, and I've seen these miracle cures die at the last hurdle. Pinning your hopes on yet another article talking of the end of HIV - by a mechanism I've seen in journals for years now - is not exactly revolutionary.

Let me know when this is a) proven to work in humans in at least Phase III trials, b) affordable and easy enough to give to the masses.

Until then, this is hot air.

[Illuminatus Primus]

Yeah, sadly, I feel like we get one of these threads every month or even couple weeks.