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Updated: 20 hours 44 min ago

New asthma treatment within five years, researchers hope

Thu, 2015-04-23 04:50

"Asthma cure could be in reach," The Independent reports. Researchers have discovered that protein molecules called calcium-sensing receptors play a pivotal role in asthma. Drugs known to block these proteins already exist.

In asthma, the immune system mistakes harmless substances, such as pollen, as a threat. White blood cells and inflammatory proteins then collect in the airways. The inflammation causes the airways to constrict, leading to the breathing difficulties associated with asthma. This study found these proteins stimulate calcium-sensing receptors, which leads to further inflammation of the airways.

The research used mouse models of asthma and human airway tissue taken from asthmatic and non-asthmatic people. The researchers found increased numbers of these calcium-sensing receptors compared with healthy lung tissue. They concluded that this is one of the reasons for the exaggerated inflammatory response that occurs in asthma.

The drug calcityrol, which is used to treat osteoporosis, is known to block the actions of the receptors. It reduced inflammation of the airways when used in mice.

However, it is not clear that calcityrol could be a "cure" for asthma, as the initial inflammatory response by the immune system would still occur.

Though calcityrol pills are safe as a treatment for osteoporosis, it is not known whether the dose required to be effective in reducing the inflammation found in asthma would be safe.

The researchers plan to develop a version of the drug that can be inhaled to maximise its effectiveness and minimise side effects. They expect human trials to commence in a couple of years.

Where did the story come from?

The study was carried out by researchers from Cardiff University, the Open University, the Mayo Clinic, and the University of California, San Francisco School of Medicine in the US, and the University of Manchester and King's College London in the UK.

It was funded by Asthma UK, the Cardiff Partnership Fund, Marie Curie Initial Training Network, the Biotechnology and Biological Sciences Research Council, and the US National Institutes of Health.

Four of the authors report they are co-inventors of a patent for the use of calcium-sensing receptor antagonists for the treatment of inflammatory lung diseases.

The study was published in the peer-reviewed journal Science Translational Medicine.

The media reported the story accurately, although headlines saying that an asthma "cure" is five years away are a little premature. No clinical studies in people have been conducted yet, and there is no guarantee they will work. However, the "five-year cure" claim came from the researchers themselves.  

What kind of research was this?

This was a set of laboratory experiments involving mice models of asthma and samples of human lung tissue. The researchers aimed to better understand the inflammation that causes narrowing of the airways in asthma.

The inflammation is an exaggerated response to various triggers, such as pollen, infections and pollutants, but sometimes no cause is identified.

Recent research found that this inflammation results in the build-up of two proteins: eosinophilic cationic protein (ECP) and major basic protein. These proteins carry multiple positive electrical charges.

The researchers wanted to test the theory that the inflammation is driven by these proteins activating another type of protein molecule called calcium-sensing receptors (CaSR) on the surface of the smooth muscle cells that line the airways.  

What did the research involve?

The researchers conducted a variety of laboratory experiments, which involved looking at human lung tissue samples taken from people with asthma and comparing them with healthy lung tissue. They then performed several studies comparing mice with a type of asthma with healthy controls.

The researchers first compared the number of CaSRs in the lung tissue of people with asthma, compared with healthy lung tissue. They then measured how the CaSRs reacted to positively charged proteins and various chemicals involved in inflammatory response, such as histamine.

They repeated the experiments using a type of drug called a calcilytic, which blocks CaSRs. Calcilytic drugs were developed as a treatment for osteoporosis, as they increase the level of parathyroid hormone by targeting CaSRs. This helps to increase the level of calcium in the blood. 

What were the basic results?

The experiments indicated there are more CaSRs in people with asthma, which are required for inflammation. Calcilytic drugs blocked the receptors.

There were three times the number of CaSRs in biopsies of smooth muscle taken from the airways of people with asthma, compared with those who do not have asthma. The same was true for biopsies of mice with a form of asthma, compared with healthy controls.

In the laboratory setting, positively charged proteins and chemicals such as histamine activated the CaSRs, causing an inflammatory response. These receptors could be blocked by the calcilytic drugs.

Mice without CaSRs in their smooth muscle cells did not have an inflammatory response to the positively charged proteins. Healthy control mice did have an inflammatory response. Calcilytic drugs were able to reduce the effect of these proteins and other inflammatory stimulants tested. 

How did the researchers interpret the results?

The researchers concluded that there are more CaSRs in the lungs of people with asthma, and this contributes to the inflammation that causes narrowing of the airways.

They say that calcilytic drugs could reduce the number of CaSRs and reduce their responsiveness. This could both "prevent as well as relieve AHR [airways hyper-responsiveness]", which is found in asthma.

The researchers do not yet know if their findings would be true for all types of asthma. 

Conclusion

This piece of research has found that CaSRs play a role in the inflammatory response seen in asthma. The early results of laboratory experiments indicate that drugs called calcilytics can dampen this inflammatory response in asthmatic human lung tissue and in mice with asthma.

Though the media described this as a "cure" for asthma, the study has not proved this. It showed that there were more CaSRs in the human lung samples from people with asthma, and compared it with healthy lung tissue.

The researchers also have not shown that calcilytics can block the receptors. What is not known is how long this effect would last and whether it would stop the lungs producing more of the excessive numbers of receptors.

It remains unclear why people with asthma in this study had an increased number of receptors, and if this is true for everyone with asthma.

The researchers predict that if calcilytics prove to be effective in clinical trials, it will take around five years for them to become available as a treatment for asthma.

This is because, although this drug has been deemed a safe treatment for osteoporosis, the researchers intend to develop the drug so it can be used as an inhaler. This would deliver it straight to the lungs to maximise the effectiveness and minimise side effects.

Drug development will involve further animal trials to work out what dose would be required to achieve clinically meaningful results, and will also test its safety. If these trials are successful, the research will progress to human trials.

This is an exciting piece of research that may provide a new treatment for asthma, but it is still early days, so there are no guarantees.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Asthma cure could be in reach as scientists make 'incredibly exciting' breakthrough. The Independent, April 22 2015

Asthma could be cured within five years after drug breakthrough. The Daily Telegraph, April 22 2015

Major asthma breakthrough as scientists discover root cause of the condition - and say a new treatment is less than 5 years away. Mail Online, April 23 2015

Cardiff University scientists discover asthma's root cause. BBC News, April 22 2015

Scientists discover root cause of asthma and believe bone drug could be cure. Daily Express, April 23 2015

Links To Science

Yarova PL, Stewart AL, Sathish V, et al. Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma. Science Translational Medicine. Published online April 22 2015

Categories: News

A magnet for mosquitoes? Blame your genes

Thu, 2015-04-23 03:30

"Mosquitoes 'lured by body odour genes','' BBC News reports. Researchers tested a series of non-identical and identical twins, and found identical twins had similar levels of attractiveness to mosquitoes.

Researchers have long known that some people are more attractive to mosquitoes than others, and some think this is to do with body odour.

Body odour is, in part, inherited through our genes, so the researchers running this study wanted to find out whether twins with identical genes shared a similar level of attractiveness to mosquitoes.

They exposed the hands of sets of identical and non-identical twins to mosquitoes to see which twin the mosquitoes preferred.

The results showed identical twins were likely to have about the same level of attractiveness to mosquitoes, while non-identical twins' results differed more. This strongly suggests there is a genetic component, in the same way there is for height and IQ.

This could explain why one half of a couple is plagued by mosquitoes on holiday, while the other will be blissfully free of any bites. The research could eventually help scientists develop better insect repellents.  

Where did the story come from?

The study was carried out by researchers from the London School of Hygiene and Tropical Medicine, the University of Florida, the University of Nottingham and Rothamsted Research. It was funded by the Sir Halley Stewart Trust.

The study was published in the peer-reviewed medical journal PLOS One, which is an open-access journal, meaning the study can be read for free online.

Generally, the media reported the study accurately, but did not question the reliability of results from the fairly small sample size (a total of 74 participants).

The Daily Telegraph suggested that using insect repellent made no difference to people with a genetic disposition to being bitten, but the study did not look at insect repellent, so we don't know if that is true. 

What kind of research was this?

This was a laboratory-based twin study, which compared the relative attractiveness to mosquitoes of pairs of twins.

The researchers wanted to know whether identical twins, who share the same genes, were more likely to have the same level of attractiveness to mosquitoes as non-identical twins, whose genes are different.

Twin studies are useful ways to show how likely a particular trait is to be inherited. However, they can't tell us any more than that – for example, which gene is involved, or how genetics affects the trait. 

What did the research involve?

Researchers took 18 pairs of identical twins and 19 pairs of non-identical twins. They tested them for attractiveness to mosquitoes by releasing the insects into a Y-shaped tube with two sections.

The twins put their hand into the top of a section, and the researchers counted the numbers of mosquitoes that flew up each side of the tube. They then looked at whether results were closer for identical twins than for non-identical twins.

The researchers did a series of experiments, testing the twins individually against clean air, and also pairing them against each other. They tried to avoid bias in the study by using randomisation to decide which side of the tube was used by which twin, and which twin was tested first.

All the twins were women and over the age of menopause. The twins had also been asked to avoid strong-smelling food such as garlic or chilli, to avoid alcohol, and to have washed their hands with odour-free soap before the experiment.

The researchers also checked the twins' temperatures to see whether body temperature had any effect on the results. The researchers used Aedes aegypti mosquitoes, which is the strain that carries dengue fever.

They analysed the data in two sets – firstly, which twin was more attractive to mosquitoes when tested against clean air, and then which was more attractive when tested against the other twin.

As well as seeing which tube the mosquitoes flew into (used to measure relative attraction), the researchers also counted how many flew at least 30 centimetres up the Y-shaped tube (used to measure flight activity).

The researchers used an average of 10 measurements for each twin to come up with estimates of the proportion of the attractiveness that was down to heritability. 

What were the basic results?

The study found identical twins were much more likely to share the same level of attractiveness to mosquitoes than non-identical twins.

The study gives an estimate that 62% (standard error 12.4%) of relative attraction (the chances of the mosquitoes choosing that person's tube) was down to heritable factors, along with 67% (standard error 35.4%) of flight activity (the chance of the mosquitoes flying 30 centimetres up the tube).

The researchers say this would put attractiveness to mosquitoes at a level similar to height and IQ in terms of how much of it is inherited.

How did the researchers interpret the results?

The researchers say their results "demonstrate an underlying genetic component detectable by mosquitoes through olfaction". In other words, the study showed genetic differences account for at least some of the relative attractiveness of people to mosquitoes, and the difference is smelt by the insects.

They go on to suggest some people may have developed a body odour that is less attractive to mosquitoes, which could then have been handed down through natural selection of favourable genes, as it would protect against diseases such as dengue fever and malaria.

However, the researchers warn that the relatively small sample size and the nature of the experiment means they can't be precise about their conclusions. The standard error rates on their estimates of heritability are quite high, showing the level of uncertainty. 

Conclusion

This research suggests the genes you inherit from your parents may determine your chances of being bitten by mosquitoes. However, the small size of the study limits how confident we can be in the results.

The researchers suggest differences in body odour determine how attractive a person is to mosquitoes. We know body odour is partly down to inherited genetic factors, so it would make sense that inherited body odour can make you more or less attractive to mosquitoes.

However, the study doesn't tell us whether the mosquitoes were attracted to people because of their body odour, or for some other reason that wasn't researched.

A lot more research needs to be done into which inherited components of body odour are linked to attractiveness to mosquitoes before scientists can use this information to produce better mosquito repellents.

At this stage, we don't know whether people who get bitten less often have less of a mosquito-attractive chemical in their body odour, or more of a mosquito-repellent chemical.

If you get bitten by mosquitoes more than other people, and one or both of your parents does too, this research suggests you might have inherited the susceptibility to being bitten.

Unfortunately, at this stage, there's not much you can do about it, except for wearing insect repellent. Wearing light, loose-fitting trousers rather than shorts, and wearing shirts with long sleeves may also help. This is particularly important during the early evening and at night, when mosquitoes prefer to feed.

If you are travelling to an area where mosquitoes are known to carry malaria, it's vital to get medical advice about which type of antimalarial medication you should take. You may need to start taking the medication before you leave the country, so it's important to plan ahead.

Read more about antimalarial medication.

Analysis by Bazian. Edited by NHS ChoicesFollow Behind the Headlines on TwitterJoin the Healthy Evidence forum.

Links To The Headlines

Mosquitoes 'lured by body odour genes'. BBC News, April 23 2015

Do YOU always get bitten by mosquitoes? Blame your parents: Being attractive to bugs is genetic, scientists say. Mail Online, April 23 2015

Chance of being bitten by mosquito is written in genes. The Daily Telegraph, April 22 2015

Some people are BORN to be bitten by mosquitoes - genes can make us more attractive to the bugs. Daily Mirror, April 22 2015

Genes and body odour determine chance of mosquito bites, scientists find. Daily Express, April 23 2015

Mosquito Bite? It May Be Your Parents' Fault. Sky News, April 22 2015

Links To Science

Fernández-Grandon GM, Gezan SA, Armour JAL, et al. Heritability of Attractiveness to Mosquitoes. PLOS One. Published online April 22 2015

Categories: News