An End to HIV: HIV Remove from Cultured Cells

https://i0.wp.com/292fc373eb1b8428f75b-7f75e5eb51943043279413a54aaa858a.r38.cf3.rackcdn.com/health-fitness_01_temp-1357384489-50e80b29-620x348.jpgAt the closing ceremony of the AIDS 2014 conference a few weeks ago in Melbourne, Australia, many of the speakers – including longtime AIDS researcher and International AIDS Society Presidential Award winner Eric Goosby – told of how utterly terrifying the disease seemed 30 years ago. And while that fear is not gone, it has since diminished, replaced by and large with a sense of hope that the disease will be eradicated.

According to UNAIDS – the Joint United Nations Programme on HIV/AIDS, which is dedicated to destroying the disease by 2030 – the medical community has learned much in the past few years and stands a good chance at accomplishing this goal. And with new advances being announced every few months, hopes for a world in which this terrible disease no longer exists all seem firmly on track.

UNAIDSConsider this latest development, which comes from the Temple University School of Medicine in Philadelphia. Here, researchers have discovered how to permanently extricate HIV-1 from human cells, effectively curing a patient of the disease. Combined with new vaccines that have shown the ability to block infection (and in some cases, even reverse it), this news may yet be reason for even greater hope.

One of the main issues in the treatment of HIV-1 is not simply that it is expensive, but that antiretroviral therapy have terrible side effects that can speed up diseases more commonly associated with aging or can cause co-infections, such as Hepatitis C, to become worse.  Added to this is that HIV is a tricky and tenacious disease that becomes part of a patient’s DNA, making it virtually impossible to eradicate.

https://i1.wp.com/images.gizmag.com/gallery_lrg/scientistseliminatehivfromhumancells.jpgHowever, researchers from Temple University School of Medicine have found a way to cut the infected genes out, potentially eradicating the virus for good and negating the need for lifelong ARV treatment. The technique uses a DNA-snipping enzyme, a nuclease, and a targeting RNA strand to hunt down the genome and cuts the HIV-1 DNA from it. The cell is able to repair its own genomes, essentially sewing itself together again, only now HIV-free.

This treatment will work in varied cell types such as the T-cells and monocytic cells that harbor HIV. In designing the molecular tools, researchers chose nucleotide sequences that do not appear in any coding sequences of human DNA to avoid what they call off-target effects, where patient’s cells or own DNA might be damaged. The technique may also be applicable against many other viruses.

There are still serious hurdles, like how to get the treatment into each, individual cell. Also, HIV-1 is known for mutations, and every patient has their own viral sequence. This means that there can be no single, prescriptive treatment for it. However, another potential upside is that there is the chance this may be used not simply as a treatment but also a vaccine as cells containing the nuclease-RNA combination do not acquire the HIV infection.

https://i1.wp.com/www.templehealth.org/AssetMgmt/getImage.aspxDr. Kamel Khalili, Professor and Chair of the Department of Neuroscience at Temple, calls it an “important step” towards the eradication of AIDS, though it is still years away from the clinical stage. As he put it:

We want to eradicate every single copy of HIV-1 from the patient. That will cure AIDS. I think this technology is the way we can do it.

Though it is not the one-shot breakthrough many have been hoping for, this enzyme-based treatment is another step along the long road towards the end of HIV and another nail in its coffin. As long as treatments exist that are not only able to treat and block, but also fight the disease, there is much reason for hope.

And be sure to check out this video from Temple University, where Dr. Khalili explains the medical breakthrough:


Sources:
gizmag.com, templehealth.org

The End of HIV: Two Men Cleared After Marrow Transplant

hiv-virus-cuFor decades, bone marrow transplants have been used for the treatment of cancer, particularly lymphoma, leukemia, and multiple myeloma. However, after three years of receiving transplants, two Australian men who were previously diagnosed with HIV have shown no signs of the AIDS virus. Moreover, one of the patient’s is the first recorded case of clearing the virus without the presence of a rare anti-HIV gene in the donor marrow.

The two patients, a 53-year-old and 47-year-old male, were diagnosed with leukaemia and lymphoma respectively at St Vincent’s Hospital in Sydney, Australia, which has been working in partnership with the University of New South Wales’ Kirby Institute. To date, there have been several reported cases of patients cleared of HIV that were related to bone marrow transplants, but this is something new entirely.

HIV_virusTimothy Ray Brown, a US citizen, was treated in 2007/8 for leukaemia with transplanted stem cells from a donor with the CCR5 delta32 mutation – which is resistant to HIV – and was reported clear of the virus. Afterward, Brown stopped taking his antiretroviral medication and remained HIV-free. In 2012, two other US patients were treated with marrow that did not contain the mutation and initially tested clear. But when they ceased taking antiretroviral medication, the virus returned.

The Australian lymphoma patient, treated in 2010, did receive one transplant of bone marrow that contained one of two copies of a gene that is possibly resistant to HIV. However, the leukaemia patient, treated in 2011, received donor marrow with no resistive gene. Both patients remain on antiretroviral medication as a precaution, since the virus may be in remission rather than completely cured.

021204-N-0696M-180The next step is to figure out why the body responds to a bone marrow transplant in a way that makes the virus retreat. One possible explanation is that the body’s immune response to the foreign cells of the transplant causes it to fight harder against HIV. This is because, while bone marrow transplant seems to be the most effective means of clearing the AIDS virus to date, it is not an acceptable risk for patients whose lives aren’t already endangered by bone cancer.

As Professor David Cooper, the study’s senior author and the director of the UNSW Kirby Institute, explained:

We’re so pleased that both patients are doing reasonably well years after the treatment for their cancers and remain free of both the original cancer and the HIV virus… The procedure itself has an up to 10 percent mortality rate. But you take that risk in someone with leukemia or lymphoma because they’re going to die without it, and the transplantation will result in cure. For someone with HIV, you would certainly not transplant them when they have an almost normal life span with standard antiretroviral therapy.

We still don’t know why these patients have undetectable viral loads. One theory is that the induction therapy helps to destroy the cells in which the virus is hiding and that any remaining infected cells are destroyed by the patient’s new immune system.. We need more research to establish why and how bone marrow transplantation clears the virus. We also want to explore the predictors of sustained viral clearance and how this might be able to be exploited without the need for bone marrow transplantation.

The team will be presenting their research 19 July 2014 at the 20th International AIDS Conference in Melbourne, Australia. There, they will be amongst such high-profile speakers as former President Bill Clinton, UNAIDS Executive Director Michel Sidibé and artist and activist Sir Bob Geldof, as well as thousands of the world’s top AIDS researchers, community leaders, people living with HIV and policy-makers at AIDS 2014.

Source: cnet.com, aids2014.com

Ending HIV: New Vaccine Holds Promise for a Cure

hiv-aids-vaccineScientists and researchers have been making great strides in the fight against HIV/AIDS in recent years. In addition to developing vaccines that have shown great promise, there have even been some treatments that have been shown to eliminate the virus altogether. And it seems that with this latest development, which was published in Nature earlier this month, there might be a treatment that can double as a cure.

Developed at the Vaccine and Gene Therapy Institute at the Oregon Health and Science University (OHSU), this new vaccine proved successful in about fifty percent of the clinical subjects that were tested, and may be able to cure patients who are currently on anti-retroviral drugs. If successful, this could mean that a preventative vaccine and cure could come in the same package, thus eliminating HIV altogether.

vaccineCurrently, anti-retroviral drugs and HIV vaccine typically aim at improving the immune response of the patient in the long term. However, they are limited in that they can never completely clear the virus from the body. In fact, aside from a very few exceptional cases, researchers have long believed that HIV/AIDS could only be contained, but not completely cured.

The OHSU team, led by Dr. Louis Picker, has been working on its own vaccine for the past 10 years. In that time, their research has shown that an immune response can in fact go beyond containment and systematically wipe the virus out of the body. As with most early vaccine candidates, the study revolves around SIV – a more aggressive virus than HIV that can replicate up to 100 times faster and, unchecked, can cause AIDS in only two years.

HIV_virusPicker and his research team created the vaccine by working with cytomegalovirus (CMV), another virus which is itself persistent, but doesn’t cause disease. In their initial tests, the vaccine was found to generate an immunoresponse very similar to that generated by CMV, where T-cells that can search and destroy target cells were created and remained in the system, consistently targeting SIV-infected cells until the virus was cleared from the body.

For the sake of their clinical trials, simian subjects were used that were infected by the HIV virus. When treated with the team’s vaccine, half of the subjects initially showed signs of infection, but those signs gradually receded before disappearing completely. This sets it apart from other vaccines which also generate an immunoresponse, but one which fades over time.

HIVAccording to Dr. Picker, it is the permanency of the T-cells that allows the immunoresponse to be consistent and slowly eradicate the virus, eventually eliminating it completely from the system. Says Dr. Picker of their trials and the possibilities for the vaccine:

The virus got in, it infected some cells, moved about in various parts of the body, but it was subsequently cleared, so that by two or three years later the monkeys looked like normal monkeys. There’s no evidence, even with the most sensitive tests, of the SIV virus still being there... We might be able to use this vaccine either to prevent infection or, potentially, even to apply it to individuals who are already infected and on anti-retroviral therapy. It may help to clear their infections so ultimately they can go off the drugs.

Currently, Picker and his the team are trying to understand why some of the vaccinated animals did not respond positively, in the hopes of further increasing the efficacy of the vaccine. Once these trials are complete, it could be just a hop, skip and a jump to getting FDA approval and making the vaccine/cure available to the open market.

Cure_for_HIVImagine, if you will, a world where HIV/AIDS is on the decline, and analysts begin predicting how long it will take before it is eradicated entirely. At this rate, such a world may be just a few years away. For those working in the field of medicine, and those of us who are around to witness it all, it’s an exciting time to be alive!

And be sure to enioy this video from OHSU where Dr. Picker speak about their vaccine and the efforts to end HIV:


Sources:
gizmag.com, nature.com

The Future of Medicine: Engineered Viruses, Nanoparticles and Bio-Absorbable Circuits

medtechThe future that is fast approaching us is one filled with possibilities, many of which were once thought to be the province of science fiction. Between tricorders and other new devices that can detect cancer sooner and at a fraction of the cost, HIV vaccines and cures, health monitoring tattoos and bionic limbs, we could be moving into an age where all known diseases are curable and physical handicaps will be non-existent.

And in the past few months, more stories have emerged with provide hope for millions of people living with diseases, injuries and disabilities. The first came just over three weeks ago from University of California, Berkley, where researchers have been working with an engineered virus which they claim could help cure blindness. As part of a gene therapy program, this treatment has been shown to effectively correct a rare form of inherited blindness.

virus-sight1For the past six years, medical science has been using adeno-associated viruses (AAV) as part of a gene therapy treatment to correct inherited retinal degenerative disease. However, the process has always been seen as invasive, since it involves injected the AAVs directly into a person’s retina with a needle. What’s more, the rpocess has shown itself to be limited, in that the injected virus does not reach all the retinal cells that need repair.

But as Professor David Schaffer, the lead researcher on the project, stated in an interview with Science Translational Medicine:

[D]octors have no choice because none of the gene delivery viruses can travel all the way through the back of the eye to reach the photoreceptors – the light sensitive cells that need the therapeutic gene.

Building on this and many more years of research, Prof David Schaffer and his colleagues developed a new process where they generated around 100 million variants of AAV and then selected five that were effective in penetrating the retina. They then used the best of these, a strain known as 7m8, to transport genes to cure two types of hereditary blindness on a group of mice.

virus-sightIn each case, the engineered virus delivered the corrective gene to all areas of the retina and restored retinal cells nearly to normal. But more importantly, the virus’ ability to penetrate the retina on its own makes the process far less invasive, and will likely be far more cost-effective when adapted to humans. And the process is apparently very convenient:

[W]e have now created a virus that you just inject into the liquid vitreous humor inside the eye and it delivers genes to a very difficult-to-reach population of delicate cells in a way that is surgically non-invasive and safe. It’s a 15-minute procedure, and you can likely go home that day.

Naturally, clinical trials are still needed, but the results are encouraging and Professor Schaffer indicated that his team are busy at work, now collaborating with physicians to identify the patients most likely to benefit from this gene-delivery technique.

nanoparticles_miceNext up, there was the announcement back at the end of May that researchers from North Carolina State and University of North Carolina Chapel Hill had found yet another medical use for nanoparticles. In there case, this consisted of combating a major health concern, especially amongst young people today: diabetes.

In a study that was published in the Journal of Agricultural and Food Chemistry, the collaborating teams indicated that their solution of nanoparticles was able to monitor blood sugar levels in a group of mice and released insulin when their sugar levels got too high. Based on the results, the researchers claim that their method will also work for human beings with type 1 diabetes.

image descriptionEach of the nanoparticles have a core of insulin that is contained with a degradable shell. When glucose levels in the blood reach high concentrations spike, the shell dissolves, releasing insulin and lowering the subject’s blood sugar. The degradable nano-network was shown to work in mice where a single injection kept blood glucose levels normal for a minimum of 10 days.

While the exact cause of this kind of diabetes is unknown, the effects certainly are. Patients living with this genetically-acquired form of the disease require several shots of insulin a day to keep their blood sugar levels under control. And even then, blindness, depression and even death can still result. What’s more, if the insulin shots are specifically calculated for the individual in question, side-effects can occur.

???????????????????????????????Hence the genius behind this new method. Not only would it relieve people who have type 1 diabetes from constantly injecting themselves, it would also remove the need to monitor their own blood sugar levels since the nanoparticles would be controlling them automatically.

In a study published recently in the Journal of Agricultural and Food Chemistry, Zhen Gu, lead author of the study claimed that the technology functions essentially the same as a pancreas. Hence another benefit of the new method, in that it could make pancreatic transplants – which are often necessary for patients with diabetes – unnecessary.

biocircuitsAnd last, but certainly not least, comes from the University of Illinois where John Rogers are developing a series of bio-absorbable electronic circuits that could help us win the war on drug-resistant bacteria. As part of a growing trend of biodegradable, flexible electronic circuits that operate wirelessly, fighting “superbugs” is just one application for this technology, but a very valuable one.

For some time now, bacteria that is resistant to antibiotics has been spreading, threatening to put the clock back 100 years to the time when routine, minor surgery was life-threatening. Some medical experts are warning that otherwise straightforward operations could soon become deadly unless new ways to fend off these infections are found. And though bacteria can evolve ways of evading chemical assaults, they are still vulnerable to direct assault.

electronics_dissolvingThis is how the new bio-absorbable circuits work: by heating up the virus. Each circuit is essentially a miniature electric heater that can be implanted into wounds and powered wirelessly to fry bacteria during healing before dissolving harmlessly into body fluids once their job is done. While this might sound dangerous, keep in mind that it takes only a relatively mild warming to kill bugs without causing discomfort or harm to surrounding tissues.

To fashion the circuits, Rogers and his colleagues used layers of utra-thin wafers and silk, material so thin that they disintegrate in water or body fluids or (in the case of silk) are known to dissolve anyway. For the metal parts, they used extra-thin films of magnesium, which is not only harmless but in fact an essential nutrient. For semiconductors, they used silicon membranes 300 nanometres thick, which also dissolve in water.

In addition to deterring bacteria, Rogers says that implantable, bio-absorbable RF electronics could be used to stimulate nerves for pain relief, and to stimulate bone re-growth, a process long proven to work when electrodes are placed on the skin or directly on the bone. Conceivably they could also be used to precisely control drug release from implanted reservoirs.

In other words, this is just the beginning. When it comes to the future of medicine, just about any barrier that was once considered impassable are suddenly looking quite porous…

Sources: sci-news.com, stm.sciencemag.org, singularityhub.com, bbc.com/future

Supercomputer Creates Atomic Model of HIV

DNA-1The ongoing fight to end HIV has been a long and arduous one, but progress is being made. In addition to potential treatments being created that have shown promise, there are also efforts being mounted to understand how the virus works at an atomic level. This is great news, for as any practitioner of medicine will tell you, understanding a disease and knowing how to strike at the heart of it is the key to stopping it and making sure future generations don’t have to fear it.

In recent years, several major breakthroughs were announced for the treatment of HIV, treatments which many heralded as cures. In January of last year, the Danish Research Council awarded funding to a group of researchers who demonstrated that HIV could be “flushed” from infected cells where it tends to congregate and protect itself. Combined with vaccinations that turbocharge the body’s immune system, this method proved effective at eliminating the HIV virus in infected cells.

HIV-budding-ColorAnother came back in November, when researchers at Caltech were even able to successfully spawn a significant amount of HIV antibodies in lab mice by using a new approach, known as Vectored ImmunoProphylaxis (VIP). An inversion of the traditional vaccination method, this new method produced plenty of HIV-preventing antibodies which they believed could be fashioned into a  vaccine.

And finally, there were the experiments being conducted over at the Washington University School of Medicine, where researchers designed a solution that employed bee venom and a nanoparticle delivery system. Knowing that bee venom is capable of killing HIV, and that the virus is thousands of times smaller than your average cell, the solution proved quite effective at filtering out the virus and killing it while leaving surrounding tissue unharmed. Taken together, these two proposed solutions have left many thinking a cure is just around the corner.

blue-waters-super-computer-at-petascale-020908Nevertheless, in order for this virus to truly be beaten, we need to understand it better. Hence why a group of scientists – using the University of Illinois’ “Blue Waters” supercomputer — have developed a new series of computer models that are finally giving researchers an atomic-level look at the formidable barrier mechanism enclosing the heart of the virus.

For example, its been known for some time that the HIV virus it’s covered in several layers of protective proteins. But beneath that outer shell resides a conical structure called the capsid, which houses the virus’ payload of genetic material. (See diagram below.) When HIV invades a cell, it’s the capsid that opens up to initiate the takeover process, allowing the virus to replicate inside the healthy host cell. Better understanding of how this mysterious delivery system operates could be one of the final steps to finding a cure.

HIVAnd that’s where the modelling software really comes into play. How and when the HIV cell opens to deliver the capsid has long eluded researchers, and as Klaus Schulten, a physicist that was part of the team that modeled the virus, pointed out: “The timing of the opening of the capsid is essential for the degree of virulence of the virus.”

Using the Blue Waters, Schulten and his associates managed to map out the model all 64 million of the capsid’s atoms. Through countless simulations, they also discovered that the capsid’s microscopic outer casing is composed of 216 hexagon-shaped proteins that fit together in a honeycomb formation. These hexagonal structures are what give the capsid it’s tough outer shell and allow it to be such a harmful and insidious killer.

AIDS_memorialThis painstakingly delicate process would have been unthinkable until just a few years ago, and represents the most complete picture of the HIV virus to date. What’s more, knowing what HIV looks like at the atomic level will help scientists to understand the timing of the virus’ delivery system. Since the opening of the virus’ protective layer is when it’s most vulnerable, Schulten and his colleagues hope to determine the precise timing of this event so a treatment can be developed that could attacks the virus at this exact moment.

Think of it as throwing a bomb into the mouth of a terrible war machine, right as it opens up its armored maw to bite you! Better yet, think of it as another step on the road to ending one of the greatest plagues humankind has ever had to deal with. Safety for the future, and justice for the victims!

Sources: popularscience.com, theweek.com, (2)