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

The Future of Medicine: New Blood-Monitoring Devices

medtechNon-invasive medicine is currently one of the fastest growing industries in the world. Thanks to ongoing developments in the fields of nanofabrication, wireless communications, embedded electronics and microsensors, new means are being created all the time that can monitor our health that are both painless and hassle-free.

Consider diabetes, an epidemic that currently affects 8% of the population in the US and is growing worldwide. In October of 2013, some 347 million cases were identified by the World Health Organization, which also claims that diabetes will become the 7th leading cause of death by 2030. To make matters worse, the conditions requires constant blood-monitoring, which is difficult in developing nations and a pain where the means exist.

google_lensesHence why medical researchers and companies are looking to create simpler, non-invasive means. Google is one such company, which back in January announced that they are working on a “smart” contact lens that can measure the amount of glucose in tears. By merging a mini glucose sensor and a small wireless chip into a set of regular soft contact lenses, they are looking to take all the pin-pricks out of blood monitoring.

In a recent post on Google’s official blog, project collaborators Brian Otis and Babak Parviz described the technology:

We’re testing prototypes that can generate a reading once per second. We’re also investigating the potential for this to serve as an early warning for the wearer, so we’re exploring integrating tiny LED lights that could light up to indicate that glucose levels have crossed above or below certain thresholds.

And Google is hardly alone in this respect. Due to growing concern and the advancements being made, others are also looking at alternatives to the finger prick, including glucose measures from breath and saliva. A company called Freedom Meditech, for example, is working on a small device  that can measure glucose levels with an eye scan.

I_Sugar_X_prototype1Their invention is known as the I-SugarX, a handheld device that scans the aqueous humor of eye, yielded accurate results in clinical studies in less than four minutes. John F. Burd, Ph.D., Chief Science Officer of Freedom Meditech, described the process and its benefits in the following way:

The eye can be thought of as an optical window into to body for the painless measurement of glucose in the ocular fluid as opposed to the blood, and is well suited for our proprietary optical polarimetric based measurements. Based on the results of this, and other studies, we plan to begin human clinical studies as we continue our product development.

Between these and other developments, a major trend towards “smart monitoring” is developing and likely to make life easier and cut down on the associated costs of medicine. A smart contact lens or saliva monitor would make it significantly easier to watch out for uncontrolled blood sugar levels, which ultimately lead to serious health complications.

I_Sugar_X_prototype2But of course, new techniques for blood-monitoring goes far beyond addressing chronic conditions like diabetes. Diagnosing and controlling the spread of debilitating, potentially fatal diseases is another major area of focus. Much like diabetes, doing regular bloodwork can be a bit difficult, especially when working in developing areas of the world where proper facilities can be hard to find.

But thanks to researchers at Rice University in Houston, Texas, a new test that requires no blood draws is in the works. Relying on laser pulse technology to create a vapor nanobubble in a malaria-infected cell, this test is able to quickly and non-invasively diagnose the disease. While it does not bring medical science closer to curing this increasingly drug-resistant disease, it could dramatically improve early diagnosis and outcomes.

malaria-blood-free-detectorThe scanner was invented by Dmitro Lapotko, a physicist, astronomer, biochemist, and cellular biologist who studied laser weapons in Belarus before moving to Houston. Here, he and his colleagues began work on a device that used the same kind of laser and acoustic sensing technology employed on sub-hunting destroyers, only on a far smaller scale and for medical purposes.

Dubbed “vapor nanobubble technology,” the device combines a laser scanner and a fiber-optic probe that detect malaria by heating up hemozoin – the iron crystal byproduct of hemoglobin that is found in malaria cells, but not normal blood cells. Because the hemozoin crystals absorb the energy from the laser pulse, they heat up enough to create transient vapor nanobubbles that pop.

malariaThis, in turn, produces a ten-millionth-of-a-second acoustic signature that is then picked up by the device’s fiber-optic acoustic sensor and indicates the presence of the malaria parasite in the blood cells scanned. And because the vapor bubbles are only generated by hemozoin, which is only present in infected cells, the approach is virtually fool-proof.

In an recent issue of Proceedings of the National Academy of Sciences, Lapotko and his research team claimed that the device detected malaria in a preclinical trial on mice where only one red blood cell in a million was infected with zero false positives. In a related school news release, the study’s co-author David Sullivan – a malaria clinician a Johns Hopkins University – had this to say about the new method:

The vapor nanobubble technology for malaria detection is distinct from all previous diagnostic approaches. The vapor nanobubble transdermal detection method adds a new dimension to malaria diagnostics, and it has the potential to support rapid, high-throughput and highly sensitive diagnosis and screening by nonmedical personnel under field conditions.

At present, malaria is one of the world’s deadliest diseases, infecting hundreds of millions of people a year and claiming the lives of more than 600,000. To make matters worse, most the victims are children. All of this combines to make malaria one of the most devastating illness effecting the developing world, comparable only to HIV/AIDS.

malaria_worldwideBy ensuring that blood tests that could detect the virus, and require nothing more than a mobile device that could make the determination quickly, and need only a portable car battery to power it, medical services could penetrate the once-thought impenetrable barriers imposed by geography and development. And this in turn would be a major step towards bringing some of the world’s most infectious diseases to heel.

Ultimately, the aim of non-invasive technology is to remove the testing and diagnostic procedures from the laboratory and make them portable, cheaper, and more user-friendly. In so doing, they also ensure that early detection, which is often the difference between life and death, is far easier to achieve. It also helps to narrow the gap between access between rich people and poor, not to mention developing and developing nations.

Sources: fastcoexist.com, news.cnet.com, businesswire.com, googleblogspot.ca, who.int

Coming Soon: A Universal Flu Vaccine?

flu_vaccineScientists have been making great strides in coming up with treatments and cures for illnesses that were previously thought to be incurable. While some of these are aimed at eliminating pandemics that have taken millions of lives worldwide (such as HIV/AIDS) others are aimed at treating the more common – but no less infectious – viruses, like the common flu.

When it comes to the latter, the difficulty is not so much in creating a cure, as it is a cure all. The flu is a virus that is constantly evolving, changing with the seasons and with each host. This requires medical researchers to constantly develop new vaccines year after year to address the latest strain, as well as specialized vaccines to address different  types – i.e. H1N1, swine, avian bird.

flu_vaccine1Luckily, a research team at Imperial College London say they have made a “blueprint” for a universal flu vaccine. Their report appeared in a recent issue of Nature Medicine. In their report, they specified that the key to creating a universal vaccine lies in targeting the core of the virus, rather than its ever-evolving DNA.

Just last year, researchers at the Friedrich-Loeffler Institute in Riems Island, Germany sought to create a similar vaccine that would target the virus’ RNA structure rather than the key proteins found in the DNA. By contrast, the Imperial researchers set about looking into T-cells, the crucial part of the immune system that is thought to be able to recognize proteins in the core.

2009_world_subdivisions_flu_pandemicTheir research began with a series of clinical examinations of the 2009 swine flu pandemic, which was produced by the combining of earlier strains of pig and bird flu. The team then compared levels of one kind of T-cells at the start of the pandemic with symptoms of flu in 342 staff and students at the university. They showed that the higher the levels of the T-cells a patient had, the milder their symptoms were.

Researchers then teased out the specific part of the immune system that offered some pandemic flu protection and which part of the virus it was attacking. from there, They began developing a vaccine that would trigger the production of these cells – known as CD8 T cells. These cells would attack the invading flu virus, ignoring the outer protein structure and focusing on the core which it had encountered before.

Influenza_virus_2008765Prof Ajit Lalvani, who led the study, told the BBC:

It’s a blueprint for a vaccine. We know the exact subgroup of the immune system and we’ve identified the key fragments in the internal core of the virus. These should be included in a vaccine. In truth, in this case it is about five years [away from a vaccine]. We have the know-how, we know what needs to be in the vaccine and we can just get on and do it.

The benefits of such a vaccine would be profound and obvious. While many of us consider the seasonal flu to be an inconvenience, it is important to note that it kills between 250,000 and 500,000 people worldwide each year. While this is a fraction of the total number of deaths attributed to AIDS (1.6 to 1.9 million in 2010, it is still a significant toll. What’s more, new pandemics have the potential to take doctors by surprise and kill large numbers of people.
t-cellHowever, the Imperial College researchers admit that it is generally harder to develop a T-cell vaccine than a traditional one designed to provoke an antibody response. The challenge will be to get a big enough of a T-cell response to offer protection and a response that will last. So while the blueprint is in place, medical researchers still have a long road ahead of them.

Prof John Oxford, of Queen Mary University of London, put it this way:

This sort of effect can’t be that powerful or we’d never have pandemics. It’s not going to solve all the problems of influenza, but could add to the range of vaccines. It’s going to be a long journey from this sort of paper to translating it into a vaccine that works.

AI-fightingfluWhat’s more, there are concerns that a T-cell vaccine would be limited when it comes to certain age groups. Jenner Institute at Oxford University, explains:

Live attenuated influenza vaccines which are given by nasal spray and will be used in children in the UK from this autumn are much better at increasing the number of influenza-specific T cells, but these vaccines only work in young children who haven’t yet had much exposure to influenza virus, so we need an alternative approach for adults.

Interestingly enough, this approach of stimulating the production of T-cells bears a striking resemblance to the work being done at the Vaccine and Gene Therapy Institute at OHSU, where researchers are working towards a vaccine that could also cure HIV. This research also appeared in Nature Medicine last month.

So not only could we be looking at a cure for both HIV and the flu in the near future, we could be looking at the containment of infectious viruses all over the world. As these two cases demonstrate, advances in medical science towards antivirals appear to be tied at the hip.

Sources: bbc.co.uk, gizmodo.com, nature.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

Ending HIV: Foot Cream Kills HIV Cells!

HIV-budding-ColorThe fight to end HIV has been long and ongoing. But in recent years, researchers have made some incredible breakthroughs in terms of treatment and vaccines. Well as it turns out, the fight may be getting a punch in the arm from a most unlikely source – an anti-fungal foot cream! Yes, not only does this common drug kill HIV, it is even more effective than some of today’s most cutting-edge drugs.

In a study performed at Rutgers New Jersey Medical School, the drug Ciclopirox was shown to completely eradicate infectious HIV when applied to cell cultures of the virus. But what was even more impressive was the fact that the virus didn’t bounce back when the drug was withheld. This means that, unlike most anti0viral drugs, it may not require a lifetime of use to keep HIV at bay.

ciclopiroxThe same group of researchers had previously shown that Ciclopirox – which was approved by the FDA and Europe’s EMA to treat foot fungus – inhibits the expression of HIV genes. Now they have found that it also blocks the essential function of the mitochondria, which results in the reactivation of the cell’s suicide pathway, all while sparing surrounding healthy cells.

This is key since one of the worst aspects of HIV – one that makes it particularly persistent, even in the face of strong antiviral treatments – is its ability to disable a cell’s altruistic suicide pathway. This “self-destruct protocol” is typically activated when a cell is damaged or infected. With the introduction of Ciclopirox, these cells are tricked into pulling a double negative, disabling the disabling of the suicide pathway.

HIVNaturally, the cream will have to be tested on humans before its efficacy as a topical HIV treatment can be tested. However, the fact that it’s already been deemed safe for one type of human use could make the regulatory process faster than usual. In fact, the researchers have noted that another FDA-approved drug now thought to help subdue HIV (called Deferiprone) skipped animal studies and went straight to human trials in South Africa.

Naturally, the Rutgers team hopes they too can go directly from their culture studies to human trials, and that the case involving Deferiprone will pave the way for a more streamlined testing process. This is likely, seeing as how there have been many breakthroughs in recent months and everyone – from researchers to patients to medical authorities – want to make treatments available as soon as possible.

Source: news.cnet.com

The Future of Medicine: Microneedle Patch

TB-resTubercle bacillus, aka. Tuberculosis or TB, is a very common, very infectious, and if untreated, very lethal disease. A well dated illness, its origins can be traced back to early Neolithic Revolution, and is often attributed to animal husbandry (specifically, the domestication of bovines). And in terms of the number of people carrying it, and the number of deaths associated with it, it is second only to HIV.

Because of this and the fact that the disease remains incurable – the only way to combat it is with early detection or experimental vaccines – it is obvious why medical researchers are looking for better ways to detect it. Currently, the standard test for tuberculosis involves inserting a hypodermic needle into a person’s arm at a very precise angle and depth, using a small trace of genetically modified TB to elicit an immuno-reaction.

TB_microneedlesAs anyone who has undergone this test knows (as a teacher, I have had to endure it twice!), it is not a very efficient or cost effective way of detecting the deadly virus. In addition to being uncomfortable, the telltale symptoms can days to manifest themselves. Hence why Researchers at the University of Washington hope to replace this test with a painless, near-automated alternative – a microneedle patch that they say is more precise and even biodegradable.

For their study, which was recently presented in the journal Advanced Healthcare Materials, the scientists used microneedles made from chitin – the material that makes up the shells sea creatures and insects and is biodegradable. Each needle is 750 micrometers long (1/40th of an inch) and is coated with the purified protein derivative used to test for tuberculosis.

TB_virusIn terms of its application, all people need do is put it on like a bandage, which ought to make testing on children much easier. For the sake of testing it, the team tested its microneedle patch on guinea pigs and found that the reaction that occurs via the hypodermic needle test also appeared using the patch. But the best aspect of it is the fact that the patch does not require any invasive or difficult procedures.

In a school news release, Marco Rolandi – assistant professor of materials science and engineering at the University of Washington and lead author of the study – had the following to say:

With a microneedle test there’s little room for user error, because the depth of delivery is determined by the microneedle length rather than the needle-insertion angle. This test is painless and easier to administer than the traditional skin test with a hypodermic needle.

medical technologyThe researchers report that they now plan to test the needle patch on humans and hope to make the patch available in the near future. However, the long-term benefits may go beyond stopping TB, as Rolandi and his team hope that similar patches will be developed for other diagnostic tests, such as those used to detect allergies. As anyone who has undergone an allergen test will tell you (again, twice!), its no picnic being pricked and scraped by needles!

As always, the future of medicine appears to be characterized by early detection, lower costs, and less invasive measures.

Sources: news.cnet.com, washington,edu, who.nt