PEOPLE AND PLACES

PEOPLE AND PLACES

Wednesday, August 10, 2011

Scientists Discovers drug that could cure all viruses - including the flu

 

The 3D image that could stop your sniffles - scientists take a virtual look inside the virus that causes the common cold

Stunning new image and video of the virus that causes the majority of common cold infections have been created using one of the world's fastest supercomputers.

Scientists hope the incredible images could lead to new viral drug treatments for the cold.

The team at the University of Melbourne have simulated the full genome of the human rhinovirus, which is responsible for almost 50 per cent of all colds.

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cold

researcher from the University of Melbourne have created a 3D view of the virus behind the common cold. This image shows the cell virtually cut open to reveal its interior

They hope to use their simulation to better understand how a new drug developed by Australian company Biota stops the virus spreading.

The drug, which is still in clinical trials, is targeted as a treatment for people with chronic lung diseases like asthma, chronic obstructive pulmonary disease and cystic fibrosis, for whom a common cold can be fatal.

The 3D image was one of the first created by a new super computer, the IBM Blue Gene Q, delivered to the University of Melbourne earlier this month.

St Vincent's Institute of Medical Research deputy director Professor Michael Parker, who led the research, said better understanding of how the rhinovirus responded to the drug had implications for a wider range of illnesses.

He said rhinovirus was related to a family of viruses that cause serious diseases including polio and meningitis.

'An increase in understanding how existing drugs work with one virus will pave the way for the development of new anti-viral medications for these related viruses and hopefully save lives around the world,' Professor Parker said.

virus

The team used one of the world's most powerful supercomputers to model the HPV virus

He worked with computer specialists from IBM and the Victorian Life Sciences Computation Initiative to create the 3D simulation.

'Supercomputer technology enables us to delve deeper in the mechanisms at play inside a human cell, particularly how drugs work at a molecular level.

'This work offers exciting opportunities for speeding up the discovery and development of new antiviral treatments and hopefully save many lives around the world,'

The super computer is the fastest in the southern hemisphere and the 31st fastest in the world, according to Dr John Wagner, manager of IBM Research Collaboratory for Life Sciences Research.

He said the computer was capable of up to 836 trillion numerical calculations a second and was also the most energy efficient computer in the world.

cell

Scientists are using the images to model how a potential tratment could work - in this image, the areas of the cell they want their drug to attach to are shown in yellow

Rhinovirus infection is linked to about 70 per cent of all asthma exacerbations with more than 50 per cent of these patients requiring hospitalisation.

Over 35 per cent of patients with acute chronic obstructive pulmonary disease (COPD) are hospitalised each year due to respiratory viruses including rhinovirus.

Out of 200 different strains of cold, the rinovirus - or nose virus - is one of the most common.

It is microscopic - it would take 50,000 rhinoviruses lined up back to back to cover just one millimetre.

‘Serial killer’ cells which can wipe out leukemia within three weeks have been developed by scientists.

Researchers have managed to treat sufferers with their body’s own cells, which have been genetically modified to attack and destroy tumours. Senior author Professor Carl June said the treatment was so powerful that tumours were ‘blown away’ in under a month with few side effects.

Researchers say their success in activating T cells, making them multiply and then kill the cancer cells is ¿unprecedented¿. Picture posed by models

Researchers say their success in activating T cells, making them multiply and then kill the cancer cells is 'unprecedented'. Picture posed by models

His team believe the breakthrough could provide a ‘roadmap’ for the treatment for cancers of the lungs and ovaries, myeloma, which attacks the bone marrow, and melanoma, the most aggressive form of skin cancer.

The treatment was trialled on three patients suffering from chronic lymphocytic leukaemia, which affects up to 4,000 people each year in the UK.

It can be managed with chemotherapy but only be cured by a bone marrow transplant, which carries a one in five risk of dying while only offering a 50/50 chance of success.  Gene transfer therapy using T cells has been a holy grail of treatment for various cancers over the past 25 years but has proved very difficult to achieve in human trials.

The researchers say their success in activating the T cells, making them multiply and then kill the cancer cells in this type of cancer, is ‘unprecedented’.

Scientists at the University of Pennsylvania’s Abramson Cancer Centre in the United States took the patients’ T cells – which are part of the immune system and have the job of fighting disease. In most forms of cancer these crucial cells are unable to distinguish tumour cells from healthy tissue, which allows the cancer to spread unchecked. But they managed to reprogram them to attack tumour cells by inserting a ‘secret ingredient’, a protein called a chimeric antigen receptor (CAR).

When this protein is on the surface of the T cells, it will bind with another protein – called CD19 – which is found in leukaemia tumour cells.

Scientists tested the cells on three patients in their 60s and 70s with a poor prognosis. A year later they are all still in good health

Scientists tested the cells on three patients in their 60s and 70s with a poor prognosis. A year later they are all still in good health. Picture posed by models

By doing this it not only kills the cancer cells, but causes other T cells to rapidly multiply so they can attack the tumour too.

Professor June said: ‘The infused T cells are serial killers. On average each fused T cell led to the killing of thousands of tumour cells – and overall, destroyed at least two pounds [one kilo] of tumour in each patient.

'SERIAL KILLER' CELLS

All three patients tested were men in their 60s and 70s with a poor prognosis, who had not responded to seven or eight types of drugs.

A year later they are all still in good health.

One of the patients was a 64-year-old man whose blood and marrow were riddled with tumour cells.

For two weeks after the procedure he showed no improvement. Then on day 14, he started to experience, chills, nausea and fever.

Tests showed an enormous increase in the number of T cells in his blood, which had given him ‘tumour lysis syndrome’, a side effect of the killing of a large number of cancer cells at once.

By day 28, he had recovered from these symptoms and his blood and bone marrow were clear of leukaemia

‘We saw at least a 1000-fold increase in the number of modified T cells, which is unprecedented, and it happened in each of the patients. Drugs don’t do that.

‘Within three weeks the tumours had been blown away, in a way that was much more violent than we ever expected.’

The study, published in the Journal of Medicine and Science Translational Medicine, showed that side effects of this process were not as bad as chemotherapy because the CAR only targeted tumour cells and B cells rather than all normal tissue.

The team now hope to test the same treat in children with leukaemia and patients with non-Hodgkins lymphoma.

Dr David Porter, who co-authored the study, said: ‘Most of what I do is treat patients with no other options, with a very, very risky therapy with the intent to cure them. This approach has the potential to do the same thing, but in a safer manner. This massive killing of tumour is a direct proof of principle of the concept.’

Dr David Grant of the charity Leukaemia and Lymphoma Research said: ‘This is very encouraging and it’s definitely a step in the right direction, although a lot more work is needed to see if it can benefit more patients as this is a small sample.

'But gene transfer therapy to strengthen immune cells is a much more attractive option than toxic anti-cancer drugs and it is an approach we are also working on in Britain, so this is promising in bringing us closer to helping more patients.’

Two British trials of this gene therapy are opening next year in London, one for acute myeloid leukaemia and the other for acute lymphoblastic leukaemia.

 

Captured in 3D: Cancer-killing white blood cells destroying diseased tissue

Cancer killing cells have been caught on camera - in 3D and in more detail than ever before.

A team of British scientists used optical laser tweezers and a powerful microscope to analyse the inner workings of the cells.

It revealed, in the highest ever resolution, how white blood cells destroy diseased tissue using 'deadly granules'.

Resolution: This is the most detailed image ever created of a cancer killing white blood cell in action

Resolution: This is the most detailed image ever created of a cancer killing white blood cell in action

Professor Daniel Davis, of Imperial College London, said: 'Actually seeing what is going on in our bodies in such minute detail is a very big deal.

'You cannot gain this knowledge any other way. You can read all about individual genes and molecules and what is supposed to happen but there is nothing as rewarding as this.

'Just like astronomers are building bigger and better telescopes to peer into the depths of space, we are developing ever more powerful microscopes to view things at the quantum level.'

The study looked at a type of white blood cell, called a Natural Killer (NK) cell, that protects the body by identifying and killing diseased tissue.

It showed how white blood cells rearrange a scaffolding of proteins on the inside of its membrane to create a hole through which it delivers the deadly enzyme-filled granules to kill diseased tissue.

Prof Davis added: 'NK cells are important in our immune response to viruses and rogue tissues like tumours.

'They may also play a role in the outcome of bone marrow transplants by determining whether a recipient's body rejects or accepts the donated tissue.'

Research: Scientists used a microscope many hundreds of times more powerful than the one pictured here to look at the cancer killing cells (picture posed by model)

Research: Scientists used a microscope many hundreds of times more powerful than the one pictured here to look at the cancer killing cells (picture posed by model)

It is hoped that learning how NK cells identify which tissues to kill, could lead to better health care for some patients.

'In the future, drugs that influence where and when NK cells kill could be included in medical treatments, such as the targeted killing of tumours,' he added.

'They may also prove useful in preventing the unwanted destruction by NK cells that may occur in transplant rejection or some auto-immune diseases.'

Physicists at Imperial used a super high-resolution microscope from the University of Oxford to see the new visual resolution of NK cell action.

The researchers immobilised an NK cell and its target using a pair of 'optical' laser tweezers so that the microscope could capture all the action at the interface between the cells.

They then watched inside the NK cell as proteins parted to create a tiny portal and the enzyme-filled granules moved to it, ready to pass out of the NK cell and onto the target to kill it. Dr Alice Brown said: 'These previously undetectable events inside cells have never been seen in such high resolution. It is truly exciting to observe what happens when an NK cell springs into action.' The contact between an NK cell and its target is only about a hundredth of a millimetre across and the minuscule proteins, known as actins, and granules change position continuously over the few minutes from initial contact until the target is killed. The microscope has to be able to capture images quickly enough and in high enough visual detail in order to reveal their activity. Most microscopes view images in the horizontal plane. And so to view an interface between two cells at any other orientation would require 'stacks' of multiple horizontal images combined to make a 3D image.

This significantly limits the speed at which cell dynamics can be viewed and reduces image quality.

Prof Paul French, of Imperial College London who helped develop the microscopy, said: 'Using laser tweezers to manipulate the interface between live cells into a horizontal orientation means our microscope can take many images of the cell contact interface in rapid succession.

'This has provided an unprecedented means to directly see dynamic molecular processes that go on between live cells.' Professor Ilan Davis, of the University of Oxford, whose group applies super resolution technique to basic cell biology research, said: 'Our microscope has given us unprecedented views inside living NK cells capturing a super-resolution 3D image of the cell structures at twice the normal resolution of conventional light microscope. 'This method, developed at University of California San Francisco by Professor John Sedat, maximizes the amount of light captured from the specimen while minimizing the amount of stray light inside the instrument.'

Breakthrough: Scientists have discovered a genetic flaw in the DNA of some cancers

Treatment breakthrough: Scientists have discovered a flaw in the DNA of some cancers. British scientists claim they are just ten years away from developing the world's first cancer killing pill - after discovering a flaw in the disease's DNA. Experts have found a mutation in some cancer cells which means the disease cannot repair its own damaged genetic structure. Scientists believe this so-called 'Achilles heel' can be exploited using gene therapy drugs in the form of pills or injections to attack the cancer's DNA. The discovery of certain cancers' inability to repair their own cells is being hailed as a breakthrough which could mean the end of painful chemotherapy treatments. The findings, led by Professor Ghulam Mufti, a leukaemia specialist at Kings College London, will be aired on BBC2's Horizon programme tonight. Prof Mufti said effective drugs were being developed by grouping cancers by the pattern of their genetic activity, rather than where they occurred in the body. He said researchers were edging closer to finding a cure for cancer by studying the DNA of tumours. The technique was made possible ten years ago when scientists first mapped all three-billion 'letters' that comprise the complete human genetic sequence. He said: 'One thing is for sure. Since the completion of the Human Genome Project, the advances have been absolutely phenomenal. 'Therefore, I'm pretty sure that over a period of time, say over the next decade, we will be able to identify the right treatment regime for a particular patient. 'As time goes on, it's probably going to be the case that the majority of cancers will have some kind of targeted therapy.' A drug undergoing medical trials at the Breakthrough Breast Cancer Research Centre in London works by attacking the cancer cells' inability to repair their own damaged genetic structure. Project leader Professor Alan Ashworth said: 'Some tumour cells can't repair their DNA properly. 'They actually don't care about repairing it. They just carry on growing fast. 'So, we've worked out a way of trying to exploit that to treat cancer.'

The drug, which has no side effects, inhibits the ability of cells to repair naturally occurring defects in their DNA. At a low concentration, healthy cells are strong enough to survive the treatment while at the same time the cancer cells that are bad at repairing their genetic make-up are destroyed.

Scan: A drug undergoing medical trials in London works by attacking the breast cancer cells' inability to repair their own damaged genetic structure

Scan: A drug undergoing medical trials in London works by attacking the breast cancer cells' inability to repair their own damaged genetic structure (file picture). Prof Ashworth added: 'At this concentration, all the mutant cells are killed but the normal cells are not really touched.

'So, potentially that translates into much more powerful treatments but much fewer side-effects as well because we're not killing normal cells.' The breakthrough could mean the difference between life and death for thousands of cancer patients. Prof Ashworth said: 'We are in the 21st century, we've got the human genome sequence, and we're still treating cancer with medieval treatments.

'We cut it out with a big knife or we burn it with radiation or we poison it with chemotherapy. 'Chemotherapy really just works by killing cells that are growing fast. There is nothing clever about it at all. 'What we're trying to do is use the genome information to develop new ways of treating the cancer itself, the genetic defects of the cancer, not the normal cells.' Scientists at the Sanger Institute in Cambridgeshire, which was at the forefront of the Human Genome Project, is also using super-computers to identify the differences in the DNA of cancerous and healthy cells from the same patient. Institute director Professor Mike Stratton said the research meant it might soon be possible to treat and even create drugs which can prevent cancer completely. Tonight's program also features a medical trial of a drug to cure cystic fibrosis using a similar method of gene therapy, which could be available on the NHS in just five years. It works by replacing the faulty gene that causes cystic fibrosis with a healthy manmade version, which is suspended in a fatty liquid and inhaled via a nebuliser. Professor Eric Alton, of the Cystic Fibrosis Gene Therapy Consortium and Imperial College London, said the research would be completed by the end of 2012. He said: 'Around that time we should get a feeling of whether that trial, for the first time in the world, has shown if patients can actually get better clinically. 'If this first trial looks good then I think we can move it quite rapidly into the NHS. 'If everything goes fantastically by the end of 2012, I think within two or three years we might be able to put it into regular treatment.'

 

 

Greatest discovery since penicillin: A cure for everything - from colds to HIV

Scientists think they may be on the verge of transforming medicine after developing a new drug which could put an end to viruses like the common cold and flu.

Scientists are developing a new drug which may cure viruses like the common cold

Scientists may have found a cure for the  common cold, flu, HIV –  and almost any other virus you can think of.

A drug that homes in on infected cells and makes them self-destruct has been created in the laboratory.

Its hit list includes human rhinoviruses – the bugs behind half of colds in adults and almost all colds in children – flu, polio, a stomach bug and deadly dengue fever.

But the drug, known by the acronym DRACO, is also expected to zap measles and German measles, cold sores, rabies and even HIV – and could be on pharmacy shelves in a decade.

Researcher Mike Rider said: ‘It’s certainly possible that there’s some virus that we aren’t able to treat but we haven’t found it yet. 'The discovery of antibiotics revolutionised the treatment of bacterial infections and we hope that this will revolutionise the treatment of viral infections. ‘There aren’t very many anti-viral drugs out there at the moment.’  Dr Rider, of the Massachusetts Institute of Technology in the U.S., has exploited cells’ natural defences against infection. When viruses infect the body, they hijack cells’ internal machinery to make copy after copy of themselves. During this procedure they create long double-stranded strings of the genetic material RNA.

Our cells usually defend themselves by making proteins that latch on to the RNA and stop the virus from breeding.

But many viruses can outsmart this defence system.

So Dr Rider has also harnessed a second natural process called apoptosis, in which diseased cells commit suicide. 

Scientists think they may be on the verge of transforming medicine after developing a new drug which could put an end to viruses like the common cold and flu.

The bottom row of images show viruses killing untreated human cells, but in the top pictures the drug used means there is no infection and cells are clear

So Dr Rider has also harnessed a second natural process called apoptosis, in which diseased cells commit suicide. 

His drug homes in on cells with double-stranded RNA, stops the infection in its tracks and then kills the cells to finish off the infection.

What is more, healthy cells are untouched, the journal PLoS ONE reports.
In lab tests, DRACO killed 15 viruses, including germs behind the common cold and two types of flu. It also saved the lives of mice given a dose of flu that should have killed them.

Amazingly, it works so quickly that if taken early enough it should stop any symptoms from appearing. Tests show it also wards off viruses, meaning it could stop people from becoming ill in the first place.

British experts welcomed the breakthrough but warned that the drug works in such an unusual way that it would have to go through years of testing before it is considered safe enough to test on people for the first time.

THE DRACOs TECHNOLOGY: HOW IT WORKS

Woman in lab with rubber gloves placing sample in Petri dish

Many viruses can outsmart human cells natural defence system - but this technology doesn't let it

When viruses infect a cell, they take over its cellular machinery for their own purpose - to create more copies of the virus

During this process, the viruses create long strings of double-stranded RNA (dsRNA), which is not found in human or other animal cells

As part of their natural defence, human cells have proteins that latch onto dsRNA, setting off a cascade of reactions that stops the virus from replicating itself

But, many viruses can outsmart that system by blocking one of the steps further down the cascade

This new technology works by combining a dsRNA-binding protein with another protein that makes cells undergo apoptosis (programmed cell suicide) — launched, for example, when a cell determines it is en route to becoming cancerous

So, when one end of the DRACO binds to dsRNA, it signals the other end of the DRACO to initiate cell suicide

Each DRACO also includes a 'delivery tag,' taken from naturally occurring proteins, that allows it to cross cell membranes and enter any human or animal cell.

However, if no dsRNA is present, DRACO leaves the cell unharmed.

World first as scientists create cancer-killing cells that can be injected into patients

  • The cells naturally occur in the body in small numbers
  • But it's hoped injecting huge quantities back into a patient could turbo-charge the immune system
  • Japanese researchers say the development paves the way for the new cancer and HIV treatments

Scientists have created cells capable of killing cancer for the first time.

The dramatic breakthrough was made by researchers in Japan who created cancer-specific killer T cells.

They say the development paves the way for the cells being directly injected into cancer patients for therapy.

Scientists have created cells capable of killing cancer for the first time. Pictured: microscopic cells being cultured to kill cancer

Scientists have created cells capable of killing cancer for the first time. Pictured: microscopic cells being cultured to kill cancer

The cells naturally occur in small numbers, but it is hoped injecting huge quantities back into a patient could turbo-charge the immune system.

Researchers at the RIKEN Research Centre for Allergy and Immunology revealed they have succeeded for the first time in creating cancer-specific, immune system cells called killer T lymphocytes.

To create these, the team first had to reprogramme T lymphocytes specialised in killing a certain type of cancer, into another type of cell called induced pluripotent stem cells (iPS cells).

These iPS cells then generated fully active, cancer-specific T lymphocytes.

These lymphocytes regenerated from iPS cells could potentially serve as cancer therapy in the future.

Previous research has shown that killer T lymphocytes produced in the lab using conventional methods are inefficient in killing cancer cells mainly because they have a very short life-span, which limits their use as treatment for cancer. To overcome the problems, the Japanese researchers, led by Hiroshi Kawamoto reprogrammed mature human killer T lymphocytes into iPS cells and investigated how these cells differentiate.

The team induced killer T lymphocytes specific for a certain type of skin cancer to reprogramme into iPS cells by exposing the lymphocytes to the 'Yamanaka factors' - a group of compounds that induce cells to revert back to a non-specialised, stage.

Japanese researchers who created cancer-specific killer T cells (pictured) say the development paves the way for the cells being directly injected into cancer patients for therapy

Japanese researchers who created cancer-specific killer T cells (pictured) say the development paves the way for the cells being directly injected into cancer patients for therapy

The iPS cells obtained were then grown in the lab and induced to differentiate into killer T lymphocytes again. This new batch of T lymphocytes was shown to be specific for the same type of skin cancer as the original lymphocytes. They maintained the genetic reorganisation, enabling them to express the cancer-specific receptor on their surface. The new T lymphocytes were also shown to be active and to produce an anti-tumour compound. Doctor Kawamoto said: 'We have succeeded in the expansion of antigen-specific T cells by making iPS cells and differentiating them back into functional T cells.

'The next step will be to test whether these T cells can selectively kill tumour cells but not other cells in the body. If they do, these cells might be directly injected into patients for therapy. This could be realised in the not-so-distant future.' The findings were published in the journal Cell Stem Cell. Dr Dusko Ilic, Senior Lecturer in Stem Cell Science, King’s College London, said: 'The study tackled a novel, quite interesting approach to cell based therapy, something that we do not usually hear about. 'Although this approach requires further verification and a lot of work needs to be done before we can think about clinical trials, the initial data are promising. 'This pioneering work definitely provides a strong foundation to build and expand our knowledge about new opportunities in cell based therapy and personalised medicine.'

Cancer killing cells have been caught on camera - in 3D and in more detail than ever before. A team of British scientists used optical laser tweezers and a powerful microscope to analyse the inner workings of the cells. It revealed, in the highest ever resolution, how white blood cells destroy diseased tissue using 'deadly granules'.

Resolution: This is the most detailed image ever created of a cancer killing white blood cell in action

Resolution: This is the most detailed image ever created of a cancer killing white blood cell in action. Professor Daniel Davis, of Imperial College London, said: 'Actually seeing what is going on in our bodies in such minute detail is a very big deal. 'You cannot gain this knowledge any other way. You can read all about individual genes and molecules and what is supposed to happen but there is nothing as rewarding as this. 'Just like astronomers are building bigger and better telescopes to peer into the depths of space, we are developing ever more powerful microscopes to view things at the quantum level.'The study looked at a type of white blood cell, called a Natural Killer (NK) cell, that protects the body by identifying and killing diseased tissue. It showed how white blood cells rearrange a scaffolding of proteins on the inside of its membrane to create a hole through which it delivers the deadly enzyme-filled granules to kill diseased tissue. Prof Davis added: 'NK cells are important in our immune response to viruses and rogue tissues like tumours. 'They may also play a role in the outcome of bone marrow transplants by determining whether a recipient's body rejects or accepts the donated tissue.'

Research: Scientists used a microscope many hundreds of times more powerful than the one pictured here to look at the cancer killing cells (picture posed by model)

Research: Scientists used a microscope many hundreds of times more powerful than the one pictured here to look at the cancer killing cells (picture posed by model) It is hoped that learning how NK cells identify which tissues to kill, could lead to better health care for some patients. 'In the future, drugs that influence where and when NK cells kill could be included in medical treatments, such as the targeted killing of tumours,' he added. 'They may also prove useful in preventing the unwanted destruction by NK cells that may occur in transplant rejection or some auto-immune diseases.' Physicists at Imperial used a super high-resolution microscope from the University of Oxford to see the new visual resolution of NK cell action. The researchers immobilised an NK cell and its target using a pair of 'optical' laser tweezers so that the microscope could capture all the action at the interface between the cells. They then watched inside the NK cell as proteins parted to create a tiny portal and the enzyme-filled granules moved to it, ready to pass out of the NK cell and onto the target to kill it.

Dr Alice Brown said: 'These previously undetectable events inside cells have never been seen in such high resolution. It is truly exciting to observe what happens when an NK cell springs into action.' The contact between an NK cell and its target is only about a hundredth of a millimetre across and the minuscule proteins, known as actins, and granules change position continuously over the few minutes from initial contact until the target is killed. The microscope has to be able to capture images quickly enough and in high enough visual detail in order to reveal their activity. Most microscopes view images in the horizontal plane. And so to view an interface between two cells at any other orientation would require 'stacks' of multiple horizontal images combined to make a 3D image.

This significantly limits the speed at which cell dynamics can be viewed and reduces image quality. Prof Paul French, of Imperial College London who helped develop the microscopy, said: 'Using laser tweezers to manipulate the interface between live cells into a horizontal orientation means our microscope can take many images of the cell contact interface in rapid succession. 'This has provided an unprecedented means to directly see dynamic molecular processes that go on between live cells.' Professor Ilan Davis, of the University of Oxford, whose group applies super resolution technique to basic cell biology research, said: 'Our microscope has given us unprecedented views inside living NK cells capturing a super-resolution 3D image of the cell structures at twice the normal resolution of conventional light microscope. 'This method, developed at University of California San Francisco by Professor John Sedat, maximizes the amount of light captured from the specimen while minimizing the amount of stray light inside the instrument.'

 

 

 

 

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