The Science Bit – Part 12: Breakthroughs in HIV research

25 05 2011

Research into finding the elusive cure for HIV, the virus that leads to AIDS, has been ongoing ever since the virus was first identified in humans in the early 1980s. Though treatment with highly active antiretroviral therapy (HAART) has dramatically improved such that the disease can be relatively effectively managed, HIV remains incurable and persistent.

Approximately 33 million people in the world are HIV positive, the majority of these in developing countries, particularly in sub-Saharan Africa. The virus, which is passed on through blood and semen, is able to cleverly evade the body’s immune system – hiding, in fact, within the white blood cells, the very cells that are supposed to seek and destroy viruses and other foreign bodies. Infection with the virus is practically symptomless, but left untreated, as the virus gradually proliferates inside the body, it overpowers the immune system and leaves the body susceptible to opportunistic infections that the patient is unable to shake off. It is this Acquired Immune Deficiency Syndrome (AIDS) that leads to death, via secondary infectious diseases such as TB, pneumonia or viral cancers.

Antiretrovirals – drugs which attempt to slow the replication of virus particles inside the body – have improved the quality of life and life expectancy for HIV positive people (who have access to these drugs) no end. Though someone with HIV will, likely, ultimately die of an AIDS-related disease, they can be expected to live a long and relatively healthy life, as opposed to a death sentence within a few short years as was previously the case. Recently, a research team from the National Institute of Allergy and Infectious Diseases (NIAID) in the US has demonstrated another important benefit of antiretroviral therapy – that starting HAART as soon as HIV infection is diagnosed, rather than when AIDS begins to become apparent, can actually reduce the ability of HIV to spread from person to person.

From a huge randomised clinical trial that began in 2005 and spanned 13 countries around the world, it was found that cross infection with HIV to a non-HIV positive partner was 96% less likely if the HIV positive partner began taking HAART while their immune system was still healthy, compared to patients who began HAART only when their CD4 T-cell count fell to below 250 cells/mm3. In fact, in the first study group, only 1 new HIV infection occurred, compared to 27 in the latter group.

And NIAID are on a roll, it seems. Another research group investigating the possibility of a vaccine for HIV infection have made a very significant breakthrough using a monkey model of infection. A potential vaccine for SIV – the simian equivalent of HIV – was trialled by giving half of a healthy study population of monkeys an injection containing the vaccine, and half a placebo. The monkeys were then injected with one of two strains of SIV. Unfortunately, the vaccine failed to protect against those given the SIVmac251 strain, but of those given the SIVsmE660 strain, 50% did not develop SIV infection.

Though of course, it is too soon to tell whether this vaccine will work equally well in humans with HIV, the results are very promising. By studying the blood cells of monkeys used in the study, the researchers were able to identify the effect of ”neutralising” antibodies that helped to prevent the SIV virus from replicating, and so affirm that this line of enquiry into an HIV vaccine is valuable. The best previous vaccination results were from a study carried out in Thailand, and that particular vaccine conferred only 31% protection against the virus, so it is clear that while a cure or a fully protective vaccination for HIV is still far away, we are certainly moving in the right direction.


The Science Bit – Part 10: Pigs lead the way in Cystic Fibrosis research

1 04 2011

Cystic Fibrosis (CF) is a recessive genetic disorder that affects approximately 8,500 people in the UK. It’s the most common life-shortening inherited disease in the world, with around 1 in 20 people being a carrier for the condition.

CF is caused by a mutation in the gene for a protein called the cystic fibrosis transmembrane conductance regulator or (thankfully) CFTR for short. This protein, in its normal state, is a channel protein that controls the movement of salts from the inside of the cell to the fluid surrounding the cells in the lungs, pancreas and other affected organs. In the sweat glands, CFTR usually works by moving salt from the sweat on the skin back into the body. When CFTR does not work properly however, too much salt and not enough water accumulates in the lungs, pancreas etc, and remains on the skin. The lack of water means that the normally lubricating tissue fluid in these organs becomes thick and sticky mucus.

The most recognisable symptoms of CF are to do with the build up of mucus in the airways, which causes unrelenting, mucusy coughing and a difficulty in breathing. Bacteria thrive on the thickened mucus, so lung infections including pneumonia are common, leading to damage of the airways and general poor health because of the inability to exercise properly to maintain fitness.

Mutated CFTR has effects elsewhere in the body, too. In the intestines, severe, chronic constipation caused by a lack of water to soften stools in the bowel can often lead to infection and rectal prolapse. Food cannot be digested properly in the small intestine, so CF patients often have difficulty in maintaining their weight and growth is stunted. The bile ducts may become blocked and cause damage to the liver. Cystic Fibrosis-related diabetes may occur as a result of the blockage of insulin in the pancreas. 97% of CF men are infertile because of an absence of the vas deferens, the tube that supplies sperm to the penis.

Given all these complications, it’s perhaps not surprising that until only a few decades ago, an infant born with CF would have been lucky to reach its first birthday. Now, although still a relatively short life expectancy, a CF sufferer might live well into their 30s and 40s, and with a successful lung transplant, even longer. Advances in treatment, including respiratory therapy, antibiotics, physiotherapy, diet and lifestyle changes have all made significant improvements to the quality of life for CF patients. But while the symptoms of CF can now be more effectively managed, there is still no cure for the disease.

A key to finding a targeted cure for CF is to understand the genetic and molecular processes that go on at the cellular level. Recently, a team of researchers from the University of Iowa made an important discovery that brings us a little step closer to the end goal of curing this disease. Pigs.

Pigs have long been used as an animal model for human disease research because in many organ systems, they have a very similar anatomy. Of course, there is much about a pig that is different, but by genetically engineering a pig model that mimics the faulty CFTR gene, the research team have been able to discover that the mutated protein has the same pathological effects in their pig model as in humans. This breakthrough means that pigs may now be used in further research to more accurately pinpoint what exactly happens to the mutated CFTR protein, and to find a way to treat it or correct it.

Using their new model, the team, whose findings were published in Science Translational Medicine last week, have already identified that the faulty CFTR protein is “misprocessed” in the cell and ends up in the wrong place, compared to the normal protein. Now that we know that pigs are analogous to humans in the manifestation of CF, they can be used to test a variety of potential new treatments, including gene therapy techniques that replace the faulty gene with a working copy, and “corrector” drugs, which aim to move the faulty protein to its proper position in the cell. The development of a pig model for studying this disease opens new doors to finding a way to beat cystic fibrosis, and new hope to its victims.

The Science Bit: Part 9 – The Human Genome Project – 10 years on

25 02 2011

The human genome projectIn 2001, the journals Science and Nature simultaneously published the results of a decade or more of groundbreaking scientific research – the Human Genome Project. But what is the Human Genome Project? Why was it done? And most importantly, what have we learnt from it?

Inside almost every one of our cells are chromosomes made up of DNA. DNA is a long, twisted molecule made up of units of 4 chemicals called adenine, thymine, cytosine and guanine and (A, T, C and G respectively), plus some sugar and phosphate molecules to hold it all together. We’ve known for many years that small sections of DNA, called genes, provide the instructions to make different proteins, and proteins are important because they are involved in just about every chemical, mechanical and structural function in the body.

The primary aim of the Human Genome Project (HGP) was to “spell out” the sequences of As, Ts, Cs and Gs for every single human gene. It was hoped that if we can do this and discover what a “normal” gene looks like, then we would also discover the genetic mutations and abnormalities that cause human diseases. Not only that, but by mapping the location of each gene on each chromosome, we might be able to use targeted drug and gene therapy to treat or even cure some of these diseases.

The announcement, in February 2001, that the human genome had been sequenced was front page news. After years of trying, and $3 billion of funding, it had finally been done. Researchers heralded the beginning of a “golden age” for genomic research, and the media were in a frenzy speculating on all the terrible diseases that may now be cured, all the wonderful new drugs that might be developed. But then, after the hype, it all went quiet.

So what has the HGP achieved in the last 10 years? We still haven’t cured cancer, or AIDS, or Alzheimer’s, and stem cell therapy is still a rather experimental treatment for some diseases rather than the miracle cure-all we hoped it would be. Was the HGP a waste of time and money?

Of course the answer to this is “no”. Though, as a result of the HGP, medicine has not advanced as much as we might like in the last decade, our underlying understanding of genomics has made great leaps and bounds. As The Economist’s Science Editor Geoffrey Carr wrote recently, the race (between rival research teams Celera and the International Human Genome Sequencing Consortium) to sequence the human genome “was not a race to the finish line, but a race to the starting line”.

So what have we learned from the HGP? Well, the very fact that the entire human genome – some 3 billion As, Ts, Cs and Gs long – could be sequenced and mapped is in itself a marvellous achievement for scientific research, and the sequencing process has been refined so that it is now much quicker, cheaper and more efficient. Despite humans being one of the most complex organisms on Earth, we’ve learned that the human genome is much smaller than we originally thought – we have around 22,000 genes, in comparison to the very recently-sequenced and very tiny water flea (Daphnia pulex), which has 31,000.

Though the head of pharmaceutical company Novartis once quipped that the HGP had yielded “data, data everywhere, and not a drug, I think”, we are now beginning to see advances in medicine too. While we have not yet witnessed a “revolution” in terms of “the diagnosis, prevention and treatment of most, if not all, human diseases”, as predicted by then-President Bill Clinton in June 2000, we have pinpointed the genetic defects that cause around 850 diseases and this is slowly but surely leading to advances in their treatment. Thanks to HGP research, several new drugs for cancer, osteoporosis and lupus are now beginning to enter the market after a decade of trials, and genetic screening is becoming more widely available for a greater range of diseases.

Despite the deficit in new discoveries that have been sensational enough to rouse the interest of the general public, the Human Genome Project and the ongoing research stemming from it, is still plugging away and helping to increase our overall understanding of genomics. If sequencing the human genome was a sprint to the start line, the race from here on is a marathon, but one that will ultimately impact greatly on biology, medicine and science as a whole.

Losing your teeth linked to losing your mind

2 02 2011

A press release I recently wrote for BioMed Central’s open access journal Behavioral and Brain Functions has again hit the newstands. I can’t find an online archive of the original release I wrote, but some lazy journos have reproduced it verbatim, so I definitely know it’s mine!

The release describes a study from the Nara Medical University in Japan whereby elderly people suffering from Alzheimer’s disease were found to lose more teeth than those without the degenerative neurological disorder. Not only is this tooth loss associated with failing to remember to brush one’s teeth and a general poor state of hygiene, but gum disease may in fact accelerate dementia by affecting the sensory neurones in the gums, leading to the brain.

Read the original article in Behavioural and Brain Functions: Relationship of tooth loss to mild memory impairment and cognitive impairment: findings from the fujiwara-kyo study

Read some of the news articles using this press release:

The Science Bit: Part 8 – Alzheimer’s Disease

28 01 2011

Alzheimer’s disease is a progressive neurodegenerative disorder that affects almost 30 million people around the world. Characterised by worsening forgetfulness, confusion and mood swings, it is a heartbreaking condition both for the sufferer and for their loved ones. Though there is currently no known cure for Alzheimer’s disease, several scientific breakthroughs have recently been made that provide encouraging insights into the disease and developments in diagnosis.

Alzheimer’s disease, a type of dementia most often seen in people over the age of 65, seems to be caused by the build-up of structures called amyloid plaques and neurofibrillary tangles in the brain. These plaques and tangles are formed from fragments of proteins that would normally be broken down into harmless substances and recycled into new molecules, but a faulty mechanism in people with Alzheimer’s disease seems to cause these protein fragments to bundle together in hard, insoluble structures that lodge in between and around nerve cells in the memory cortex of the brain. As a result of both amyloid plaques and neurofibrillary tangles, the normal transport connections are inactivated and nerve cells begin to die.

A primary research target into understanding more about Alzheimer’s disease is to look at the reasons why these proteins go wrong. Since proteins are the products of genes, genetic investigation is key and so far, at least 4 different genes have been implicated. Researchers are also very interested in the link between Alzheimer’s and Down’s Syndrome, since people with this chromosome disorder tend to age more quickly than most people and also suffer from Alzheimer’s-like symptoms. In fact, a study from the UT Southwestern Medical Center earlier this year (Netzer et al., PLoS One 5(6): e10943) found that reducing the levels of an Alzheimer’s-related protein in the brain seems to improve the ability for mice with a Down’s-like syndrome to learn.

Another line of enquiry looks at the relationship between cholesterol and Alzheimer’s disease. Cholesterol is usually thought of a “bad” substance that causes heart disease, but a certain amount of cholesterol is actually essential for the synthesis of the cell membranes. Smaller amounts of excess cholesterol in the blood is usually broken down into chemicals called oxysterols, which in turn are then eliminated in the liver and further broken down into harmless substances. Researchers have discovered that people with Alzheimer’s disease seem to have higher levels of certain types of oxysterols in their blood, which suggests that there may be a connection between a faulty cholesterol metabolism and brain degeneration. Building a profile of the types and levels of oxysterol in a person’s blood may help doctors to diagnose Alzheimer’s more quickly.

The most recent breakthrough in Alzheimer’s research, published in Cell this month (Reddy et al., Cell 144(1), 132-142), comes from a team at the Scripps Research Institute which has developed a new way to identify diseases, including Alzheimer’s disease. Using thousands of different synthetic molecules called “peptoids”, the team were able to identify disease-specific biomarkers in mouse blood samples. It is hoped that now, by passing the technique over to Alzheimer’s experts, further research may one day lead to the development of a simple blood test that will identify these biomarkers for Alzheimer’s disease in individuals who have yet to show symptoms, thus allowing earlier diagnosis and treatment.

Household bugs – a risk to human health?

27 01 2011

The evolution of antibiotic resistant bacteria – so-called “superbugs”, such as MRSA – is a real problem in our hospitals. People entering hospital for routine operations are more and more frequently suffering from complications arising from nosicomial infection with a strain of bacteria that is not killed with conventional antibiotics.

New research published in BMC Microbiology describes findings that implicate farm animals and insects in the propagation of antibiotic resistant bacteria. Because antibiotics are frequently given to farm animals in order to increase meat yield, the natural bacteria in their intestines is developing resistance to these antibiotics. The bacteria, which leave the animal’s body via the faeces, can be spread to humans by dung-dwelling cockroaches and flies.

Read the original article in BMC Microbiology: Insects in confined swine operations carry a large antibiotic resistant and potentially virulent enterococcal community

Read the press release I wrote on this story at EurekAlert: Household bugs – a risk to human health?

Read some of the news articles using this press release:

It’s grim up North! Northern men have dirtier hands than Southerners

12 01 2011

A study recently published in the open access journal BMC Public Health has found that men “oop North” seem more likely to carry harmful bacteria on their hands. Researchers from the London School of Hygiene and Tropical Medicine took swabs from the hands of commuters travelling through some of the UK’s major rail stations, and the further north they went, the more bacteria – and the more harmful bacteria – they found.The dirtiest men were found to be students and people who worked with soil.

Read the original article at BMC Public Health: Male commuters in north and south England: risk factors for the presence of faecal bacteria on hands

Read the press release I wrote on this article at BioMed Central: It’s grim up North! Northern men have dirtier hands than Southerners

Read some of the articles that used my press release:

The story was also discussed on BBC Radio 5 Live (no longer available)

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