Asthma, what is it and how do we treat it?Read More
Today, 2nd May 2017, is World Asthma Day, a day dedicated to asthma prevention, diagnosis and treatment.
What is asthma?
Asthma is a heterogeneous disease characterised by chronic airway inflammation and variable airway obstruction that is reversible, either spontaneously or after treatment. It affects people of all ages and often starts in childhood, although it can also appear for the first time in adults. The disease is long-term or chronic and the prevalence in different countries varies widely, but the disparity is narrowing due to rising prevalence in low and middle income countries and plateauing in high- income countries.
An estimated 300 million people worldwide suffer from asthma, with 250,000 annual deaths attributed to the disease. It is estimated that the number of people with asthma will grow by more than 100 million by 2025. Approximately 250,000 people die prematurely each year from asthma. Almost all of these deaths are avoidable.
There’s currently no cure for asthma, but there are simple treatments that can help keep the symptoms under control so it doesn’t have a significant impact on the patient´s life. Some people, particularly children, may eventually grow out of asthma, but for many it is a lifelong condition.
Treatment with inhaled corticosteroids is the dominating anti-inflammatory treatment during asthma and is recommended at all stages of the disease, except for the mildest. The inhaled corticosteroids can be combined with long-acting beta-2 agonists, these are symptom-controllers that are helpful in opening the airways. (Reference: http://www.aaaai.org/conditions-and-treatments/asthma)
In addition, leukotriene modifiers can further relieve symptoms for some patients, as leukotrienes are important mediators in asthma. Produced by eosinophils, mast cells and macrophages they contribute to chronic inflammation during asthma.
New drug treatments
In addition to traditional treatments, new drugs are being developed to relieve the different symptoms of asthma. One of them, anti-IL-5 (Mepolizumab) has recently been approved both in Sweden and the UK.
This drug is used to help patients with severe, difficult to treat asthma. Approximately five per cent of asthma patients fall within this category, but since asthma is such a prevalent disease, this proportion adds up to quite a few people.
Mepolizumab targets severe eosinophilic asthma – where the inflammation of the airways is linked to a particular type of white blood cell (eosinophils). It is a humanised monoclonal antibody that binds to interleukin-5 (IL-5) and hinders IL-5 from binding to its receptor on eosinophils, leading to a decrease of eosinophils in blood, tissue and sputum. It is believed that around 40% of people with severe asthma will have an eosinophilic phenotype – meaning that they may be able to benefit from the new treatment.
Mepolizumab is administered through sub-cutaneous injection every two to four weeks. Despite the high cost of the drug doctors are positive.
“A very badly affected group of patients can get help and if a few of these individuals can get a better control over their asthma, their need for healthcare would decrease and their ability to work would increase. This could mean economic benefits for both healthcare and the society,” says Christer Jansson, professor and consultant at the lung and allergy clinic at Akademiska sjukhuset, Uppsala, Sweden.
Benralizumab is another drug targeting eosinophilic asthma, that is undergoing testing right now. Unlike mepolizumab it uses a different pathway; targeting the IL-5 receptor, causing eosinophil apoptosis (cell death). One potential advantage of benralizumab is that it can be given less often, every two months instead of every two weeks, which may lower the cost of the treatment.
Into the future
Hopefully these drugs are just the first of a new line of treatments available targeted at severe asthma. Research is needed to help patients with other types of severe asthma and better diagnostic tests are needed to help ensure that people can have a confirmed diagnosis quickly. This will mean appropriate treatments can be offered, freeing people to go to work, school, raise families and live unrestricted lives that are not overshadowed by asthma.
What are your thoughts on future treatments and diagnostics for asthma? Let me know @fraidifrida
Are we the generation to eliminate one of the biggest killers in human history?Read More
April 25th marks World Malaria Day, a day dedicated to promoting the global efforts to understand and control Malaria – one of the biggest killers in human history. A disease so deadly, some researchers believe it may be responsible for the deaths of almost half of all people who have ever lived.
Caused by different forms of the Plasmodium parasite, there are four types of this life-threatening disease of varying severities. In its most serious form it can affect the kidneys and brain, causing anaemia, coma and death. Malaria is present in over 90 countries and roughly half of the population is currently at risk of catching the disease, with the greatest burden being in the least developed areas where there is very limited access to life-saving preventions, diagnoses and treatments.
How is malaria spread?
It is quite fitting that this lethal disease is transmitted to people through the deadliest animal on the planet – the mosquito. The Mosquito itself does not benefit from transmitting the malaria parasite, it is merely the disease vector – but, having survived for hundreds of millennia, with a population in the trillions and the ability to lay hundreds of eggs at a time, it’s an organism that certainly makes a very effective carrier.
A mosquito bite is simply the beginning of the process for the plasmodium sporozoites (an immature form of the parasite), which have accumulated in the mosquitos’ salivary glands, ready to be released into your body once your skin has been penetrated. This is where the human infection begins, and the sporozoites parasitize the liver, where they appear dormant as they mature and multiply to merozoites. The cells they inhabit eventually erupt and the merozoites are released into the bloodstream, cunningly disguising themselves with the liver cell membranes to avoid an immune attack. This is where they begin their second assault, causing red blood cells to erupt and release toxins that stimulate an immune response – it is this that leads you to experience flu-like symptoms such as fever. In severe cases, if the blood-brain barrier is breached, this can lead to a coma, neurological damage or even death.
The current situation
There have been large-scale efforts to eradicate malaria in the last 75 years. For example, during the WHO’s anti-malarial campaign in the 1950s and 60s DDT was used which, at the time, was hailed as kryptonite to mosquitoes. Bill Gates has famously stated that the world’s fight against malaria is one of the greatest success stories in the history of human health, and yes, over the last couple of decades there certainly has been a significant decline in the global burden of malaria. In fact, since 2000, almost 60 countries have seen a drop of at least 75% in new malaria cases, contributing to a 37% drop globally. However, the 2016 WHO report shows that in 2015 alone more than 400,000 people died of malaria and 214 million were infected. So, the job is far from finished.
Target Malaria – a new approach
There have been remarkable advances in gene-editing technologies in recent years, so one of the main focuses in malaria research lies in exploring different strategies to reduce or modify the populations of Anopheles mosquitoes; specifically, the three species in this genus that are responsible for most of the malaria transmission in Africa. Target Malaria is a not-for-profit research consortium that aims to develop and share technology for malaria control. Their focus is reducing the number of the deadliest malaria-transmitting mosquitoes in Africa – Anopheles gambiae. Specifically, they are interested in targeting female mosquitoes, as these are the only ones that bite, and this is an effective approach to control population size. Target Malaria are investigating the potential of using nuclease enzymes, that cut specific sequences of DNA, to modify mosquito genes. By changing certain genes, malarial resistance, female infertility and almost exclusively male offspring can be induced. The researchers are inserting genes that code for these enzymes into mosquito eggs, with the hope of affecting their reproduction. An example of this research involves nucleases that cut the X chromosome while males are making their sperm, resulting in mainly male offspring. Alongside this, researchers are also investigating how to disrupt the fertility of female mosquitoes to reduce the number of offspring, as well as engineering mosquitoes that are unable to transmit malaria.
These scientists are utilising a method called ‘gene drive’, a powerful emerging technology that is able to override genetic rules to ensure all offspring acquire a trait, as opposed to just, half as would normally be the case, allowing the trait to be spread extremely quickly.
Nowhere are the devastating effects of malaria as obvious as in sub-Saharan Africa, where hundreds of thousands fall victim each year, making up 90% of the total mortality count for the disease. Target Malaria researchers are currently working in Mali, Uganda and Burkina Faso with Bana, a small village in Burkina Faso, having the potential to be the site of a revolutionary genetic experiment. At Imperial College London, gene drive mosquitoes are being designed to have reduced female offspring or the inability to reproduce in general, and are then planned to be released into the wild in Bana. Their hope is that this would nearly eradicate Anopheles gambiae, to a point sufficient to prevent malaria transmission.
So what are we waiting for?
For one thing, the communities need to be prepared for the release. Firstly, there needs to be education, not just regarding genetic engineering and the impact the release will have, but also basic genetics – which may be a challenge in a community where there is no equivalent term, even for the word gene. Additionally, there are still years before scientists will be able to fully develop test gene drive mosquitoes in this manner.
If an experiment of this type is successful in the future, not only could this essentially eradicate malaria, but it could also pave the way for eliminating other mosquito-borne diseases such as dengue fever or even other insect-transmitted diseases like Lyme disease. However, humans have never before changed the genetic code of a free-living organism on this scale and released it into the wild. This genetic-engineering technology is very powerful and definitely needs to be treated as such. But, with millions dying and suffering at the hands of malaria each year, should we look to do this sooner rather than later?
What do you think? Could we be the generation that ends one of the oldest and deadliest diseases in human history? Tweet me your thoughts @PranikaAtNotch.
Progress for patients with Parkinson’s diseaseRead More
On April 11th this year, World Parkinson’s Day will mark 262 years since James Parkinson was born and 200 years since he published his essay ‘On the Shaking Palsy’, which led to an official recognition of Parkinson’s Disease (PD). Today, it’s estimated that over 10 million people worldwide have PD. Despite widespread awareness of PD and its most common symptoms, scientists don’t know why PD develops, and there is no cure. As a result, treatment has been restricted mostly to drugs that ease the symptoms, and physiotherapy.
Researchers have been exploring PD extensively over the decades and are closer to understanding its underlying biology. These studies are leading to promising new drug treatments that are now entering clinical trials, as well as new possibilities for reversing PD by repairing patients’ brains. Here’s a quick summary of a few recent developments.
What is Parkinson’s?
PD is a progressive neurodegenerative disease. It causes nerve cells in parts of the brain that control movement to stop working and die off. In healthy brains, these neurons rely on the brain chemical, dopamine, to communicate with one another. Replacing the lost dopamine in PD patients’ brains has therefore been the focus of many treatments over the decades.
Although PD is a degenerative disease that is more common in older people, we now know it is not specifically a disease of old age: around five to ten per cent of PD patients are aged under 50. Currently, there are no biochemical tests for PD; diagnosis depends on observation of the patient by a clinical and/or neurological specialist.
Every patient’s experience of PD can be different, but common symptoms include tremors – especially in hands or fingers when the limbs are at rest, slowness of movement and stiff, rigid muscles. These effects can be painful as well as debilitating, and become progressively worse.
It’s a challenging disease to diagnose, predict and treat for several reasons. The speed at which the disease progresses and symptoms develop can vary from one patient to the next. Sometimes Parkinson’s is hereditary, but most of the time it’s not. More recently, scientists have discovered that Parkinson’s can also affect parts of the brain that don’t control movement, resulting in a variety of ‘non-motor’ effects that include mental illness such as depression.
Since the 1960s, PD patients have been prescribed drugs such as levodopa that increase dopamine in the brain. Such drugs help to improve patients’ mobility but are associated with unpleasant side effects that typically get worse over time and can contribute to the patient’s illness. It’s also common for patients on these drugs to experience sudden “off periods” when the treatments just stop working. In the long term, the side effects can seriously outweigh the benefits of the treatment and there is an urgent need for more effective drugs.
Finding new drug treatments
In recent years, scientists have learned more about the biology of Parkinson’s and how it causes nerve cells to malfunction. Researchers have been particularly interested in Lewy bodies, which are clumps of proteins that typically appear in the affected brain cells of PD patients. One of the main components of Lewy bodies is alpha-synuclein, and a number of experiments have shown that alpha-synuclein could play a role in the development of PD. As a result, drug companies are now investigating whether new therapies targeting alpha-synuclein could prevent PD development, or at least slow down the disease progression in patients. Clinical trials have recently started for some of these potential new drugs and the Parkinson’s community is eagerly awaiting the results.
Replacing damaged brain cells
An alternative approach to PD treatment is to transplant new cells into the brain, to replace the dead cells. Several different methods have been tried over the past few decades, including transplants of dopamine-producing foetal cells and, more recently, stem cell grafts. In the late 1980s, researchers at Lund University in Sweden successfully transplanted dopaminergic foetal cells into the brains of 18 patients with Parkinson’s. The majority of the patients showed long-term improvements in their symptoms and some of them were able to stop taking levodopa.
One of the patients from the study died recently, 24 years after the transplant, and post-mortem analysis provided a detailed picture of what happened to the transplant in the patient’s brain. During his life, the patient had initially responded very well to the transplant: he was able to come off levodopa completely for a few years, then continued for ten years on a reduced drug dose. The patient then started to decline and, by 18 years after the transplant, the patient’s disease symptoms were similar to those shown before the study. In line with these behavioural observations, post-mortem analysis of the patient’s brain showed that the transplanted cells had grown into the damaged brain areas and successfully formed new nerve connections (re-innervation). However, signs of Parkinson’s disease, such as Lewy bodies, were found in a small proportion of the transplanted cells.
Further transplant studies have been carried out since the pioneering Lund study, but with mixed success. However, it has been generally accepted that cell replacement could be beneficial for PD, and researchers are now investigating modified approaches using stem cells that can develop into dopamine-producing neurons when transplanted into the brain.
Stem cells have attracted a lot of interest for repairing human brains and other organs in recent years. These immature cells have not yet differentiated into their final cell type (such as skin, muscle or brain cells) and, therefore, have important advantages for brain repair. Importantly, stem cells are much more widely available than foetal tissue because stem cells can come from a variety of sources, including adult humans, and can also be grown in the lab. A special type of inducible stem cell (iPSC) can be manipulated to grow into almost any type of cell that’s specialised for the brain or body region of interest. Scientists are now researching iPSCs as well as other types of stem cell for transplanting into Parkinson’s brains, and it’s expected that these will soon be ready for testing in PD patients.
Tailoring treatments to patients
Another area of research that could be beneficial for PD in the future is personalised medicine. This approach relies on collecting individual patients’ biological information and using that to decide the best course of treatment for the patient. For example, the data might include details about a patient’s immune system, their genes, and levels of hormones and other proteins or biomarkers. This can provide important information about the patient’s stage of disease and response to treatment. In turn, this helps with their prognosis and finding more tailored treatment regimes. Although much work has yet to be done before new Parkinson’s treatments become widely available, the personalised medicine approach could be particularly beneficial for PD given the variation seen in patients’ symptoms, disease progression and response to existing treatments.
What are your thoughts on future treatments for PD? Let me know Kate@Notch
Lindvall O, Rehncrona S, Brundin P et al. (1989). Arch Neurol 46(6): 615-631.
Lindvall O, Brundin P, Widner H et al. (1990). Science 247(4942): 574-577.
Stoker TB & Barker RA (2016). Regenerative Medicine 11(8): 778-786.
Parkinson’s Disease Foundation
The Michael J Fox Foundation