NewsMarket: Health

Showing posts with label Health. Show all posts

Monday, February 20, 2012

Body clock 'alters' immune system

Will the time affect medicine?

The time of the day could be an important factor in the risk of getting an infection, according to researchers in the US.

They showed how a protein in the immune system was affected by changes in the chemistry of the body through the day.

The findings, published in the journal Immunity, showed the time of an infection changed its severity.

An expert said drugs were likely to take advantage of the body clock in the near future.

Plants, animals and even bacteria go through a daily 24-hour routine, known as a circadian rhythm. Jet lag is what happens when the body gets out of sync with its surroundings after crossing time zones.

It has been known that there are variations in the immune system throughout the day. Researchers are now drilling down into the details.

The immune system needs to detect an infection before it can begin to fight it off. Researchers at Yale University School of Medicine were investigating one of the proteins involved in the detection process - Toll-like receptor nine (TLR9), which can spot DNA from bacteria and viruses.

In experiments on mice, the scientists showed that the amount of TLR9 produced and the way it functioned was controlled by the body clock and varied through the day.

Immunising mice at the peak of TLR9 activity improved the immune response, the researchers said.

They said humans with sepsis, blood poisoning, were known to be at a greater risk of death between 02:00 and 06:00.

Time link

When testing mice, the severity of sepsis depended on the time of day infection started and coincided with changes in TLR9 activity.

Prof Erol Fikrig, who conducted the study at Yale University, said they had found a "direct molecular link between circadian rhythms and the immune system", which could have "important implications for the prevention and treatment of disease".

He added: "It does appear that disruptions of the circadian clock influence our susceptibility to pathogens."

Dr Akhilesh Reddy, who is researching circadian rhythms at the University of Cambridge, said it was "known long ago" that timing had an impact on the immune system, but this was "one of the first forays" into the reasons why.

The implications for healthcare could mean that drugs need to be given at certain times of day in order to make them more effective, or drugs could be made which actually target the body clock to put the immune system into its most active phase.

Dr Reddy said drug companies were "all switching onto this" and were "now screening drugs at different times of the day".

He could see the body clock impacting medicine "within 10 years".

Pancreatic cancer: Trial drug MRK003 shows promise

Doctors want to improve the prognosis of this aggressive cancer

Scientists say they may have found a new weapon against pancreatic cancer after promising early trial results of an experimental drug combination.

Giving the chemotherapy agent gemcitabine with an experimental drug called MRK003 sets off a chain of events that ultimately kills cancer cells, studies in mice show.

Patients are now testing the treatment to see if it will work for them.

The Cancer Research UK-funded trials are being carried out in Cambridge.

Father-of-two Richard Griffiths, 41, from Coventry, has been on the trial since being diagnosed with pancreatic cancer in May 2011.

"After six cycles of treatment, a scan showed the tumours had reduced and so I have continued with the treatment," he said.

"The trial gives you hope - I really feel I can do this with the science behind me."

Aggressive cancer

Cancer Research UK says it is prioritising research into pancreatic cancer because the survival rate still remains dismally low.

About 8,000 people in the UK are diagnosed with pancreatic cancer each year, and the disease is the fifth most common cause of cancer death in the UK.

Survival rates are very low in relation to other cancers, and the length of time between diagnosis and death is typically short, usually less than six months.

The most recent data for England show that about 16% of patients survive the disease beyond 12 months after diagnosis - prompting the need for new treatments.

Professor Duncan Jodrell, who is leading the trials at the University of Cambridge, said: "We're delighted that the results of this important research are now being evaluated in a clinical trial, to test whether this might be a new treatment approach for patients with pancreatic cancer, although it will be some time before we're able to say how successful this will be in patients."

In total, about 60 patients with advanced pancreatic cancer will be recruited for the first Phase I/II clinical trial.

Wednesday, February 15, 2012

Stem cells used to 'heal' heart attack scars

Scar tissue forms after a heart attack

Damage caused by a heart attack has been healed using stem cells gathered from the patient's own heart, according to doctors in the US.

The amount of scar tissue was halved in the small safety trial reported in the Lancet medical journal.

The authors said there was also an "unprecedented" increase in new heart muscle.

The British Heart Foundation said it was "early days", but could "be great news for heart attack patients".

A heart attack happens when the organ is starved of oxygen, such as a clot blocking the flow of blood to the heart.

As the heart heals, the dead muscle is replaced with scar tissue, but because this does not beat like heart muscle the ability to pump blood around the body is reduced.

Doctors around the world are looking at ways of "regenerating" the heart to replace the scar tissue with beating muscle. Stem cells, which can transform into any other type of specialised cell, figure prominently in their plans.

Heart to heart

This trial, at the Cedars-Sinai Heart Institute, was designed to test the safety of using stem cells taken from a heart attack patient's own heart.

Healing the heart

This is the second group of doctors to report using cells taken from a heart to heal a heart.

In November 2011, another safety trial showed the cells could be used to heal the hearts of heart failure patients who were having heart bypass surgery.

The heart is not the only source for these stem cells and other fields are much further ahead.

The largest ever trial of stem cell therapy in heart attack patients is about to get under way in Europe.

The BAMI trial will inject 3,000 heart attack patients with stem cells taken from their bone marrow within five days of the heart attack.

Cardiac cells 'heal heart damage'

Within a month of a heart attack, a tube was inserted into a vein in the patient's neck and was pushed down towards the heart. A sample of heart tissue, about "half the size of a raisin", was taken.

This was taken to the laboratory where the stem cells were isolated and grown. Up to 25 million of these stem cells were then put into the arteries surrounding the heart.

Twenty five patients took part in the trial. Before the treatment, scar tissue accounted for an average of 24% of their left ventricle, a major chamber of the heart. It went down to 16% after six months and 12% after a year.

Healthy heart muscle appeared to take its place. The study said the cells, "have an unprecedented ability to reduce scar and simultaneously stimulate the regrowth of healthy [heart] tissue".

One of the researchers Dr Eduardo Marban said: "While the primary goal of our study was to verify safety, we also looked for evidence that the treatment might dissolve scar and regrow lost heart muscle.

"This has never been accomplished before, despite a decade of cell therapy trials for patients with heart attacks. Now we have done it.

"The effects are substantial, and surprisingly larger in humans than they were in animal tests."

Dr Iqbal Malik: ''This is one small step''

However, there was no increase in a significant measure of the heart's ability to pump - the left ventricle ejection fraction: the percentage of blood pumped out of the left ventricle.

Prof Anthony Mathur, who is co-ordinating a stem cell trial involving 3,000 heart attack patients, said that even if the study found an increase in ejection fraction then it would be the source of much debate.

He argued that as it was a proof-of-concept study, with a small group of patients, "proving it is safe and feasible is all you can ask".

"The findings would be very interesting, but obviously they need further clarification and evidence," he added.

Prof Jeremy Pearson, associate medical director at the British Heart Foundation, said: "It's the first time these scientists' potentially exciting work has been carried out in humans, and the results are very encouraging.

"These cells have been proven to form heart muscle in a petri dish but now they seem to be doing the same thing when injected back into the heart as part of an apparently safe procedure.

"It's early days, and this research will certainly need following up, but it could be great news for heart attack patients who face the debilitating symptoms of heart failure."

Bone marrow stem cells give 'some' heart healing

Scar tissue forms after a heart attack

Bone marrow stem cell therapy offers "moderate improvement" to heart attack patients, according to a large UK review of clinical trials.

The analysis by the Cochrane Collaboration looked at 33 trials involving more than 1,700 patients.

It said longer-term studies were needed to see if the experimental therapy affected life expectancy.

The review comes a day after doctors reported the first case of using heart cells to heal heart attack damage.

If a patient survives a heart attack, dead heart muscle is replaced with scar tissue - leaving the patient weaker and possibly on a lifetime of medicine.

Researchers are beginning to show that taking cells from a heart, growing millions of new heart cells in the laboratory and pumping those back into the heart may reduce scar tissue and lead to new heart muscle.

“Start Quote

Stem cell therapy may also reduce the number of patients who later die or suffer from heart failure, but currently there is a lack of statistically significant evidence based on the small number of patients treated so far”

Dr Enca Martin-RendonLead researcher

However, the trials are at a very early stage and in only a handful of patients. Using a similar technique with cells taken from the bone marrow, which is a prime source of stem cells, has a much longer pedigree.

The report by Cochrane pooled the data from all 33 bone marrow trials which had taken place up to 2011.

It concluded that bone marrow therapy "may lead to a moderate long-term improvement" in heart function which "might be clinically very important".

Longer life uncertain

It said there was still no evidence of "any significant effect on mortality" in comparison with standard treatment. However, this may be due to the size of the studies and that patients were followed for a short period of time.

Lead author Dr Enca Martin-Rendon, from NHS Blood and Transplant at the John Radcliffe Hospital in Oxford, said: "This new treatment may lead to moderate improvement in heart function over standard treatments.

"Stem cell therapy may also reduce the number of patients who later die or suffer from heart failure, but currently there is a lack of statistically significant evidence based on the small number of patients treated so far."

Prof Anthony Mathur, from Barts and the London School of Medicine and Dentistry, is leading the largest ever trial of stem cells in heart attack patients.

It starts this year, however, he told the BBC that the results could come quite quickly. Three thousand patients across Europe will take part. They will be injected with stem cells five days after a heart attack and then followed for two years to see if the therapy affects life expectancy.

Prof Peter Weissberg, medical director at the British Heart Foundation, said: "This review reflects the consensus of opinion about these trials - cell therapy has a modestly beneficial effect.

"Despite that, no-one knows why, or even if, cell therapies will translate into better survival or sustained improvement in damaged hearts. It's much too early to judge the likely long-term benefits."

Bacteria used to fight sleeping sickness

The sleeping sickness parasite gets into the bloodstream

Scientists believe they have found a way to beat sleeping sickness using a bacterium against the tsetse fly host that spreads the disease to humans.

In the same way that we have friendly bacteria in our intestines, the tsetse fly harbours bacteria in its midgut, muscle and salivary glands.

Experts in Belgium have genetically modified these "good bugs" so they attack the culprit parasite carried by the fly.

But work is needed to hone the process.

The latest findings are published in the open access journal Microbial Cell Factories.

The disease

Sleeping sickness, or human African trypanosomiasis, is a potentially fatal disease that plagues many regions of Africa.

Although the number of people being infected with the disease has been going down thanks to better diagnosis and treatment, there were still more than 7,000 new cases recorded in 2010.

The parasite causing sleeping sickness is transmitted to humans through the bite of the infected tsetse fly.

This causes fever, headaches, aching joints and itching. Then follows the second stage of disease as the parasites cross the blood-brain barrier to infect the central nervous system.

The person then becomes confused, poorly co-ordinated and experiences the sleep disturbances which give the disease its name.

Without treatment, sleeping sickness is fatal.

But current therapies often have unpleasant side-effects.

Alternatives

The drug most commonly used to treat the condition is a derivative of arsenic developed more than 50 years ago. And the treatment can be excruciatingly painful and potentially fatal. Often described by patients as "fire in the veins," between 5% and 20% of those treated die of complications from the injected drug.

And so scientists are seeking alternatives.

The Belgium team at the Institute of Tropical Medicine in Antwerp have focused on finding a way to destroy the sleeping sickness parasite - trypanosome - that the tsetse fly carries.

They found bacteria called Sodalis glossinidius, which naturally live in the fly and can be used to mount an attack from the inside.

Altering the genes of the bacteria led it to release fragments of antibodies known as nanobodies against the parasite.

With more work, the researchers hope to be able to produce targeted nanobodies which could kill or block the development of trypanosome.

Dr David Horn of the London School of Hygiene and Tropical Medicine said: "This is a neat and promising concept. The goal now will be to develop a deliverable toxin, not necessarily a nanobody, which exhibits anti-trypanosomal activity in the fly."

Thursday, February 9, 2012

Alzheimer's brain plaques 'rapidly cleared' in mice

Sections of Alzheimer's, left, and healthy brain tissue showing brain shrinkage with the condition

Destructive plaques found in the brains of Alzheimer's patients have been rapidly cleared by researchers testing a cancer drug on mice.

The US study, published in the journal Science, reported the plaques were broken down at "unprecedented" speed.

Tests also showed an improvement in some brain function.

Specialists said the results were promising, but warned that successful drugs in mice often failed to work in people.

The exact cause of Alzheimer's remains unknown, but one of the leading theories involves the formation of clumps of a protein called beta-amyloid. These damage and kill brain cells, eventually resulting in memory problems and the inability to think clearly.

Clearing protein plaques is a major focus of Alzheimer's research and drugs are already being tested in human clinical trials.

In the body, the role of removing beta-amyloid falls to apolipoprotein E - or ApoE. However, people have different versions of the protein. Having the ApoE4 genetic variant is one of the biggest risk factors for developing the disease.

Helping hand

Scientists at the Case Western Reserve University in Ohio were investigating ways of boosting levels of ApoE, which in theory should reduce levels of beta-amyloid.

They tested bexarotene, which has been approved for use to treat cancers in the skin, on mice with an illness similar to Alzheimer's.

Plaques, in brown, form around brain cells, in blue, which kills parts of the brain

After one dose in young mice, the levels of beta-amyloid in the brain were "rapidly lowered" within six hours and a 25% reduction was sustained for 70 hours.

In older mice with established amyloid plaques, seven days of treatment halved the number of plaques in the brain.

The study said there were improvements in brain function after treatment, in nest building, maze performance and remembering electrical shocks.

Researchers Paige Cramer said: "This is an unprecedented finding. Previously, the best existing treatment for Alzheimer's disease in mice required several months to reduce plaque in the brain."

In people?

The research is at a very early stage, and drugs often do not make the leap from animal experiment to human treatment.

Fellow researcher Prof Gary Landreth said the study was "particularly exciting and rewarding" and held the "potential promise of a therapy for Alzheimer's disease".

However, he stressed that the drug had been tested in only three "mouse models" which simulate the early stages of the disease and are not Alzheimer's.

Alzheimer's disease

Alzheimer's disease is the most common cause of dementia
Symptoms include loss of memory, mood changes, and problems with communication and reasoning
No one single factor has been identified as a cause for Alzheimer's disease - a combination of factors, including age, genes, environment, lifestyle and general health are implicated
Source: Alzheimer's Society

He warned people not to "try this at home", as the drug had not been proven to work in Alzheimer's patients and there was no indication of what any dose should be.

"We need to be clear, the drug works quite well in mouse models of the disease. Our next objective is to ascertain if it acts similarly in humans," he said.

His group is preparing to start trials in a small group of people to see if there is a similar effect in humans.

The disease is likely to become more common as people live longer. The Alzheimer's Society predicts the number of people with dementia will reach a million by 2021 in the UK alone.

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There are a number of drugs in development that aim to clear amyloid from the brain, and the jury is still out on whether this approach will be successful as a treatment for Alzheimer's”

Dr Simon RidleyAlzheimer's Research UK

Its research manager, Dr Anne Corbett, said: "This exciting study could be the beginning of a journey towards a potential new way to treat Alzheimer's disease.

"However, this is very early days. People with Alzheimer's should not rush to get this drug, as we need much more research to establish if it has benefits for humans."

Dr Simon Ridley, head of research at Alzheimer's Research UK, said the findings were "promising" but any effect was still unproven in people.

"There are a number of drugs in development that aim to clear amyloid from the brain, and the jury is still out on whether this approach will be successful as a treatment for Alzheimer's."

David Allsop, professor of neuroscience at Lancaster University, said: "I would say that the results should be treated with cautious optimism.

"It looks promising in the mouse model but in recent years, these types of experiments in mice have not translated well into humans."

Wednesday, February 8, 2012

Gene therapy 'gave me sight back'

Tami Morehouse: 'It's just incredible to see'

There was some improvement after the genetic fault in one eye was corrected four years ago.Three US citizens who lost their sight in childhood have reported a dramatic improvement in vision after having gene therapy in both eyes.

Now, one woman has described her joy at seeing her children's faces, after her second eye was treated.

The research increases hopes that gene therapy can be used in a range of eye conditions, said a UK expert.

The three have Leber's Congenital Amaurosis (LCA), a rare inherited disease caused by defects in a gene encoding a protein needed for vision.

It appears at birth or in the first months of life, leading to severely impaired vision, involuntary eye movements and poor night vision.

The disorder, which can be caused by 'mistakes' in more than 10 different genes, prevents normal function of the retina; the light-sensitive layer of cells at the back of the eye.

Several teams around the world are carrying out early trials of gene therapy in blindness, including experts at the Philadelphia Children's Hospital and the University of Philadelphia, US.

Only a handful of patients worldwide have received the treatment to boost a faulty gene underlying an inherited form of blindness.

Tami Morehouse on regaining her sight

"Life's just so much easier at a level that most people take for granted. Yes, seeing my kids' faces - my son has big huge black eyes, my daughter has big beautiful blue eyes, and I have to look very carefully to see them, but I can. Everyday things were lost to me and now I have a bit of that back and I just can't tell you what that means."

The US researchers revealed in 2008 that 12 people with LCA had recovered some vision after being injected in one eye with an engineered virus carrying the gene RPE65.

In a follow-up study they treated the other eye of three of them, and found it improved their sight even more.

The subjects could see better in dim light and two were able to find their way around obstacles.

The results were revealed in the latest edition of the journal Science Translational Medicine.

The principal investigator of the study, Dr Jean Bennett, said the patients could now do things they could never do before, such as walking around at night, going shopping for groceries and recognising people's faces.

She told the BBC: "We've shown that it is possible to safely treat both eyes of people with this particular form of retinal deficiency using a gene-based treatment and further we've demonstrated that the brain understands what the retina is seeing."

MRI scans showed the brain could "see" the newly-treated eye.

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I think it will be a stepping stone to treating more common forms of blindness in both eyes”

Dr Jean BennettUniversity of Pennsylvania

Dr Manzar Ashtari, from The Children's Hospital of Philadelphia, who carried out the brain scans, told the BBC: "We saw the brain gets activated - the brain after treatment responded to the visual stimuli."

'Incredibly valuable'

One of the three patients who took part in the clinical trial, Tami Morehouse, told the BBC how her vision gradually returned, opening up a whole new world for her.

Even though she can't see well enough to read or drive a car, she can now make-out her children's faces, watch them play baseball and see the light change over Lake Erie, where she lives.

She said: "Life is so much easier at a level that most people take for granted. Any amount of vision that you can get when you have almost nothing is incredibly valuable."

The researchers now hope to treat the second eye of the remaining nine patients, and extend the clinical trial.

Dr Bennett said: "I think it will be a stepping stone to treating more common forms of blindness in both eyes."

Commenting on the study, Clara Eaglen, policy and campaigns manager at the Royal National Institute of Blind People (RNIB), UK, said: "The early results of this small scale trial are encouraging, but clearly, a lot more research is needed to maximise the benefits of gene therapy techniques and understand how they can then be turned into effective treatments for a variety of more common degenerative eye conditions."

Professor Robin Ali of the Institute of Ophthalmology at University College London leads a UK team carrying out a similar trial of gene therapy.

He said: "This is confirmation that it is possible to administer gene therapy safely to the second eye of patients.

"This is reassuring and increases the prospect of this type of therapy for treatment of a wide range of eye conditions."