Blog search results for Tag: disease

Health & Wellbeing

It’s quite likely that most people who end up in the vicinity of a scorpion will more than likely beat a hasty retreat, not least because they can impart a potentially life threatening dose of venom should one get stung.

But scientists are now finding that the venom from these creatures, along with snakes and spiders, could be beneficial in treating heart attacks. Scorpion venom in particular contains a peptide that has been found to have a positive impact on the cardiovascular system of rats with high blood pressure. Reporting their findings in Journal of Proteome Research, scientists from Brazil, Canada and Denmark say that they now have a better understanding of the processes involved.

 An emperor scorpian

Emperor Scorpion 

Scorpion venom is a complex mixture of molecules including neurotoxins, vasodilators and antimicrobial compounds, among many others. Individual venom compounds, if isolated and administered at the proper dose, could have surprising health benefits, the researchers say.

One promising compound is the tripeptide KPP (Lys-Pro-Pro), which the researchers say is part of a larger scorpion toxin. KPP was shown to cause blood vessels to dilate and blood pressure to decline in hypertensive rats.

 A blood vessel on organic tissue

A blood vessel on organic tissue

To understand how KPP worked, the researchers treated cardiac muscle cells from mice, in a Petri dish, with KPP and measured the levels of proteins expressed by the cells at different times using mass spectrometry. They found that KPP regulated proteins associated with cell death, energy production, muscle contraction and protein turnover. In addition the scorpion peptide triggered the phosphorylation of a mouse protein called AKT, which activated another protein involved in production of nitric oxide, a vasodilator.

Treatment with KPP led to dephosphorylation of a protein called phospholamban, which led to reduced contraction of cardiac muscle cells. Both AKT and phospholamban are already known to protect cardiac tissue from injuries caused by lack of oxygen. The researchers said that these results indicate that KPP should be further studied as a drug lead for heart attacks and other cardiovascular problems.

 

Conceptual image for cardiovascular problems . 


Sustainability & Environment

The first splashes of yellow are starting to appear across our gardens and parks so it must be nearly daffodil time. There are over 10,000 narcissus cultivars and ‘Carlton’ is the most commonly grown of all. There are 5,300 hectares of this cultivar grown in the UK for cut flowers alone. This cultivar was first registered in 1927 and it is estimated that there are now 350,000 tons of it (or 9450 million bulbs)! Is this the most massive plant taxon on earth? 
 narcissus cultivars

March in the SCIence Garden

Narcissus was the classical Greek name of a beautiful youth who became so entranced with his own reflection that he killed himself and all that was left was a flower – a Narcissus. The word is possibly derived from an ancient Iranian language. But the floral narcissi are not so self-obsessed. As a member of the Amaryllidaceae, a family known for containing biologically active alkaloids, it is no surprise to learn that they contain a potent medicinal agent. 

Narcissus (and in particular this cultivar) are an excellent source of galanthamine, a drug more commonly associated with snowdrops (Galanthus spp.). Galanthamine is currently recommended for the treatment of moderate Alzheimer’s disease by the National Institute of Health and Clinical Excellence (NICE) but is very effective in earlier stages of the disease too. 

 Galanthamine

Galanthamine

Today, part of the commercial supply of this molecule comes from chemical synthesis, itself an amazing chemical achievement due to the structural complexity of the molecule, and partly from the natural product isolated from different sources across the globe. In China, Lycoris radiata is grown as a crop, in Bulgaria, Leucojum aestivum is farmed and in the UK the humble daffodil, Narcissus ‘Carlton’ is the provider.

 Narcissus

Narcissus ‘Carlton’ growing on large scale

Agroceutical Products, was established in 2012 to commercialise the research of Trevor Walker and colleagues who developed a cost effective, reliable and scalable method for producing galanthamine by extraction from Narcissus. They discovered the “Black Mountains Effect” – the increased production of galanthamine in the narcissus when they are grown under stress conditions at 1,200 feet. With support from Innovate UK and other organisations, the process is still being developed. Whilst not a full scale commercial production process just yet, the work is ongoing. As well as providing a supply of the much needed drug, this company may be showing the Welsh farming community how to secure additional income from their land. They continue to look for partners who have suitable land over 1000 ft in elevation. 

The estimated global patient population for Alzheimer’s in 2010 was 30 million. It is expected to reach 120 million by 2050.  The global market for Alzheimer’s disease drugs for 2019 was US$ 2870 million. 


Health & Wellbeing

flowers gif 

Originally posted by naturegifs

Treatments for Alzheimer’s disease can be expensive to produce, but by using novel cultivation of daffodils, one small Welsh company has managed to find a cost-effective production method of one pharmaceutical drug, galanthamine. 

The disease has been identified as a protein misfolding disease which leads to the break down, or death, of neurons and synapses in the brain. The pathology of the disease is complicated and involves many processes and enzymes.

 brain xray

Alzheimer’s disease is the cause of 60-70% of dementia cases. 

Alzheimer’s disease is a neurodegenerative disease with a range of symptoms, including language problems, memory loss, disorientation and mood swings. Despite this, the cause of Alzheimer’s is very understood. The Alzheimer’s disease drug market is currently worth an estimated US$8bn. 

The main current form of treatment is acetylcholinesterase inhibitors(AChEIs). Acetylcholine is a neurotransmitter that is mainly involved in motor function, particularly in muscles, and its production has been found to decrease in Alzheimer’s patients as they age. AChEIs inhibit the breakdown of acetylcholine, strengthening the brain’s responses. 

Agroceutical Products: on the road to sustainable Alzheimer’s medication. Video: Innovate UK  

Galanthamine is a natural product that is also an acetylcholinesterase inhibitor. It has been used in medicine since the 1950s and is commonly used for the treatment of Alzheimer’s disease. The drug can be isolated in small quantities from flowers such as Caucasian snowdrop, daffodils and red spider lilies, or produced synthetically at a high cost. 


Health & Wellbeing

flowers gif 

Originally posted by naturegifs

Treatments for Alzheimer’s disease can be expensive to produce, but by using novel cultivation of daffodils, one small Welsh company has managed to find a cost-effective production method of one pharmaceutical drug, galanthamine. 

The disease has been identified as a protein misfolding disease which leads to the break down, or death, of neurons and synapses in the brain. The pathology of the disease is complicated and involves many processes and enzymes.

 brain xray

Alzheimer’s disease is the cause of 60-70% of dementia cases. 

Alzheimer’s disease is a neurodegenerative disease with a range of symptoms, including language problems, memory loss, disorientation and mood swings. Despite this, the cause of Alzheimer’s is very understood. The Alzheimer’s disease drug market is currently worth an estimated US$8bn. 

The main current form of treatment is acetylcholinesterase inhibitors(AChEIs). Acetylcholine is a neurotransmitter that is mainly involved in motor function, particularly in muscles, and its production has been found to decrease in Alzheimer’s patients as they age. AChEIs inhibit the breakdown of acetylcholine, strengthening the brain’s responses. 

Agroceutical Products: on the road to sustainable Alzheimer’s medication. Video: Innovate UK  

Galanthamine is a natural product that is also an acetylcholinesterase inhibitor. It has been used in medicine since the 1950s and is commonly used for the treatment of Alzheimer’s disease. The drug can be isolated in small quantities from flowers such as Caucasian snowdrop, daffodils and red spider lilies, or produced synthetically at a high cost. 


Health & Wellbeing

 alzheimers

Almost half of world’s adults aged 85 and over have Alzheimer’s Disease.

The amyloid-B precursor protein (APP) plays a key role in the development of the amyloid plaques that are the hallmark of Alzheimer’s disease. Now, researchers claim to have identified thousands of genetic variants of the APP gene that codes for the protein in the brains of patients with the most common form of Alzheimer’s disease, known as late-onset or sporadic AD (SAD). 

The study reveals for the first time how this genetic variation occurs – by a mechanism involving the enzyme reverse transcriptase, the same type of enzyme used by HIV to infect cells.

 plaques in the brain

APP forms plaques in the brain, as shown above in a light micrograph.

Our findings provide a scientific rationale for immediate clinical evaluations of HIV antiretroviral therapies in people with AD,’ says Jerold Chun, senior VP of Neuroscience Drug Discovery at Sanford Burnham Prebys Medical Discovery Unit (SBP), an idea that the researchers say is supported by the relative absence of proven AD in ageing HIV patients on antiretroviral medication.

The APP gene variants were created by reverse transcription, the researchers note, when RNA acts as a template to form complementary DNA sequences that are then reinserted back into the original genome.

Discovery of possible Alzheimer’s treatment. Video: Sanford Burnham Prebys Medical Discovery Institute

This process of gene recombination – which occurs each time cells divide to make new ones – has not previously been reported in nerve cells (neurons) in the brain but could also help to explain the complexity and diverse functions of our brain cells.


Health & Wellbeing

Clinical trials for a new coeliac disease vaccine are being fast tracked by the US Food and Drugs Administration (FDA) due to promising initial results.

gluten free bread

Coeliac disease is caused by an autoimmune response to gluten and affects approximately 1 in 100 people worldwide. Those affected must eat a gluten-free diet, or they may experience uncomfortable digestive symptoms, mouth ulcers, fatigue and anaemia.

What’s the big deal with gluten? Video: TED-Ed

Problems occur for coeliac disease patients when they are exposed to gluten – a protein found in wheat and other grains – and the immune system is triggered to attack the body. This results in inflammation, mainly in the intestines, and causes the subsequent acute symptoms related to the condition.

Over 90% of coeliac disease patients carry immune recognition genes known as HLA-DQ2.5. These genes are human leukocyte antigen (HLA) genes, which usually relate to specific diseases.

 injection needle

ImmusanT, a leader in the development of therapies for autoimmune disorders, has developed a vaccine that targets patients carrying the HLA-DQ2.5 genes. This novel therapeutic vaccine, known as Nexvax2, works by reprogramming specific T cells that are responsible for triggering an inflammatory response when gluten is consumed.

 


Health & Wellbeing

Roughly 60% of the 12 million animal experiments in Europe each year involve mice. But despite their undoubted usefulness, mice haven’t been much help in getting successful drugs into patients with brain conditions such as autism, schizophrenia or Alzheimer’s disease. So too have researchers grown 2D human brain cells in a dish. However, human brain tissue comprises many cell types in complex 3D arrangements, necessary for true cell identity and function to emerge.

Researchers are hopeful that lab grown mini-brains – tiny 3D tissues resembling the early human brain – may offer a more promising approach. ‘We first published on them in 2013, but the number of brain organoid papers has since skyrocketed, with 300 just last year,’ says Madeline Lancaster at the Medical Research Council’s Laboratory of Molecular Biology lab in Cambridge, UK.

 pippette and petri dish

Lancaster was the first to grow mini-brains – or brain organoids – as a postdoc in the lab of Juergen Knoblich at the Institute of Molecular Biotechnology in Vienna, Austria. The miniature brains comprised parts of the cortex, hippocampus and even retinas, resembling a jumbled-up brain of a human foetus.

‘We were stunned by how similar the events in the organoids were to what happens in a human embryo,’ says Knoblich. To be clear, the brain tissue is not a downsized replicate. Lancaster compares the blobs of tissue to an aircraft disassembled and put back together, with the engine, cockpit and wings in the wrong place.

Growing mini brains to discover what makes us human | Madeline Lancaster. Video: TEDx Talks  

‘The plane wouldn’t fly, but you can study each of those components and learn about them. This is the same with brain organoids. They develop features similar to the human brain,’ she explains.


Careers

Each year SCI’s Scotland group runs a competition where students are invited to write a short article describing how their PhD research relates to SCI’s strapline: where science meets business.

Jack Washington (right), a Pure and Applied Chemistry PhD student at the University of Strathclyde, was the overall winner of this year’s competition. His article ‘Clavulanic acid - The fight against antibiotic resistance’ is reproduced here:

Clavulanic acid - The fight against antibiotic resistance

 The molecular structure of clavulanic acid

The molecular structure of clavulanic acid. Image: Wikimedia Commons

If you were to say that cancer is the biggest threat to public health you would be wrong.

One of the most pre-eminent risks to human existence is antibiotic resistance. Antibiotics are medicines used to fight bacterial infections. However, bacteria are fighting back at an alarming rate. Without effective antibiotics, we could live in a world where infections borne from a simple wound could be deadly. Routine surgeries would no longer be possible. Whilst this bacterial apocalypse seems drastic, it’s a very real possibility, and one we could face in the near future.

 Alexander Fleming

Alexander Fleming. Image: Wikimedia Commons

Antibiotics are part of a multibillion-pound industry and are essential for life as we know it today. In 1928, the scientist Alexander Fleming, from Ayrshire in Scotland, serendipitously discovered penicillin. This chance discovery revolutionised the treatment of bacterial infections and spurred a wealth of antibiotic research. 88 years later, in the nearby town of Irvine, I started my PhD project in this field.

Penicillin is a β-lactam antibiotic, which made up of molecules containing a chemical entity known as a β-lactam. This β-lactam is a covalent warhead – a harpoon that grips its bacterial victim and doesn’t let go. This harpoon interrupts bacterial cell wall formation, causing the bacteria to rupture and die. 

Maryn McKenna: What do we do when antibiotics don’t work any more? Video: TED

However, bacteria can retaliate by producing aggressive enzymes that destroy this warhead. Another member of the β-lactam family, clavulanic acid, can thwart these enzymes. Clavulanic acid has weak antibiotic activity on its own so is used in a double act with another antibiotic, amoxicillin, to fight antibiotic-resistant bacteria as a team.

 

Sustainability & Environment

The IHNV virus has spread worldwide and is fatal to salmon and rainbow trout – costing millions in sales of lost farmed fish. The current vaccination approach requires needle injection of fish, one by one. Now, however, Seattle-based Lumen Bioscience has come up with a new technology to make recombinant vaccines in a type of blue-green algae called Spirulina that costs pennies to produce and can be fed to fish in their feed.

To be effective, oral vaccines have not only to survive the gut environment intact but must also target the appropriate gut-associated immune cells. The approach developed by Lumen overcomes many of the problems with complex and expensive encapsulation strategies attempted in the past, according to CEO Brian Finrow.

fish gif

Originally posted by zandraart

‘[It] focuses on a new oral-vaccine platform [using] engineered Spirulina to express high amounts of target antigen in a form that is both provocative to the immune system – ie generates a desirable immune response that protects against future infection – and can be ingested orally without purification, in an organism that has been used as a safe food source for both humans and fish for decades.’

To produce the new oral vaccine, the Lumen researchers first developed a strain of Spirulina that manufactures recombinant proteins in its cell walls that the salmon immune system recognises as IHNV viruses. They then rapidly grew the strain in a large-scale indoor production system – requiring only light, water, salt and trace nutrients – and harvested and dried all the raw Spirulina biomass. This dried powder can then be fed to the fish.


Materials

The eighth in its series, the Kinase 2018: towards new frontiers 8th RSC/SCI symposium on kinase design took place at the Babraham Institute, Cambridge – a world-leading biomedical science research hub.  

The focus of the event was to provide a space for the discussion of the ever-evolving kinase inhibitor landscape, including current challenges, opportunities and the road ahead.

A kinase is an enzyme that transfers phosphate groups to other proteins (phosphorylation). Typically, kinase activity is perturbed in many diseases, resulting in abnormal phosphorylation, thus driving disease. Kinases inhibitors are a class of drug that act to inhibit aberrant kinases activity.

Cell signalling: kinases & phosphorylation. Image: Phospho Biomedical Animation

Over 100 delegates from across the world working in both academia and industry attended the event, including delegates from GlaxoSmithKline, AstraZeneca, Genentech, and Eli Lilly and Co.

The event boasted world-class speakers working on groundbreaking therapeutics involving kinase inhibitors, including designing drugs for the treatment of triple negative breast cancer, complications associated with diabetes, African sleeping sickness and more.


How can kinase inhibitors revolutionise cancer treatment?

 Tsetse flies

Tsetse flies carry African sleeping sickness. Image: Oregon State University/Flickr

The keynote speaker, Prof Klaus Okkenhaug from Cambridge University, spoke about how the immune system can be manipulated to target and kill cancer cells by using kinase inhibitors.

Klaus is working on trying to better understand the effects of specific kinase inhibitors on the immune system in patients with blood cancer.

He also explored how his work can benefit those with APDS, a rare immunodeficiency disorder, which he helped to elucidate on a molecular level.


Solving graft rejection, one kinase at a time

 Organ grafts

Organ grafts are a surgical procedure where tissue is moved from one site in the body to another. Image: US Navy

Improving tolerance to organ grafts is at the forefront of transplantation medicine. James Reuberson from UCB Pharma UK, highlighted how kinase inhibitors can be utilised to improve graft tolerance.  

James took the delegates on a journey, describing the plight of drug discovery and development, highlighting the challenges involved in creating a drug with high efficacy. While still in its infancy, James’ drug shows potential to prolong graft retention.


Agrifood

The world’s largest agriculture companies have joined forces to invest in new and innovative technologies that will hopefully eradicate malaria by 2040. The ‘Zero by 40’ campaign was launched at the annual Commonwealth Heads of Government meeting held in London last week.

The programme has the support of the Bill & Melinda Gates Foundation and the Innovative Vector Control Consortium, based in Liverpool, UK, as well as companies BASF, Bayer, and Syngenta – among others.

 Mosquitos 2

Mosquitos are known vectors of the malaria virus. Image: James Gathany/Centre for Disease Control

Malaria affects over 200 million people each year – most cases are found in Africa but the disease is still prevalent in South East Asia and in the Mediterranean. Although the number of cases has been slowly falling year-on-year, this progress is threatened by insecticide resistance.

It is estimated that four out of five malaria cases have been prevented through long-lasting insecticide-treated bed nets (LLINs) and indoor residual spraying (IRS) techniques. The campaign is a continued sign of commitment from the agriculture industry, with companies already having produced innovative solutions to tackle the global issue.

Both Syngenta and Bayer have introduced new IRS products – either in the final stages of development or already employed across Africa. BASF has developed a new generation mosquito net with an insecticide derived from crop use to deter resistant mosquitos.

 Insecticides used in agriculture

Insecticides used in agriculture are used as control mechanisms for the mosquito population.

‘Our industry collaboration, supported by our funders including the Bill & Melinda Gates Foundation and the UK’s Department of International Development, is starting to bear fruit and is saving lives today,’ said Nick Hamon, CEO of IVCC.

‘But we still have a long way to go to achieve our ambition of ending the disease burden of malaria by 2040,’ Hamon said. ‘This new initiative will not only secure the current supply of solutions, but will pave the way for desperately needed new forms of chemistry and new vector control tools to reduce the disease burden of malaria which still affects millions of people.’


Health & Wellbeing

Using 2D imaging techniques to diagnose problems with the heart can be challenging due to the constant movement of the cardiac system. Currently, when a patient undergoes a cardiac MRI scan they have to hold their breath while the scan takes snapshots in time with their heartbeat.

Still images are difficult to obtain with this traditional technique as a beating heart and blood flow can blur the picture. This method becomes trickier if the individual has existing breathing problems or an irregular heartbeat.

These problems can lead to trouble in acquiring accurate diagnostics.  

 beating heart still image

Now, a team based at the Cedars-Sinai Medical Center in California, US, have detailed a new technique – MR Multitasking – that can resolve these issues by improving patient comfort and shortening testing time.

‘It is challenging to obtain good cardiac magnetic resonance images because the heart is beating incessantly, and the patient is breathing, so the motion makes the test vulnerable to errors,’ said Shlomo Melmed, Dean of the Cedars-Sinai Center faculty.

 An MRI Scanner

An MRI Scanner. Image: Wikimedia Commons

‘By novel approaches to this longstanding problem, this research team has found a unique solution to improve cardiac care for patients around the world for years to come.’

By developing what the team consider a six-dimensional imaging technique, the Center has embraced the motion of a heartbeat by capturing image data continuously – creating a product similar to a video.

heartbeat detection gif

Originally posted by suckerfordeep

‘MR Multitasking continuously acquires image data and then, when the test is completed, the program separates out the overlapping sources of motion and other changes into multiple time dimensions,’ said Anthony Christodoulou, first author and PhD researcher at the Center’s Biomedical Imaging Research Institute.

‘If a picture is 2D, then a video is 3D because it adds the passage of time,’ said Christodoulou. ‘Our videos are 6D because we can play them back four different ways: We can playback cardiac motion, respiratory motion, and two different tissue processes that reveal cardiac health.’

Your guide to a cardiac MRI. Video: British Heart Foundation

Testing ten healthy volunteers and ten cardiac patients, the team said the group found that the method was more comfortable for patients and took just 90 seconds – significantly quicker than the conventional MRI scan used in hospitals. For each of the participants, the scan produced accurate results.

The team are now looking to extend its work into MR Multitasking by focusing on other disease areas, such as cancer.


Health & Wellbeing

The US is in the midst of a healthcare epidemic. Tens of thousands of people are dying each year from opioid drugs, including overdoses from prescription painkillers such as OxiContin (oxycodone) and the illicit street drug heroin, and each year the numbers rise.

The opioid epidemic is currently killing almost twice as many people as shootings or motor vehicle accidents, with overdoses quadrupling since 1999. According to Gary Franklin, medical director of the Washington State Department of Labour and Industries and a professor of health at the University of Washington, the opioid epidemic is ‘the worst man-made epidemic in modern medical history in the US’.

 Montgomery Ohio

Montgomery, Ohio, is at the centre of the epidemic, with the most opioid-related deaths per capita this year. Image: Wikimedia Commons

Incredibly, an influx of synthetic opioids is making the problem worse. Fentanyl, a licensed drug to treat severe pain, is increasingly turning up on the street as illicit fentanyl, often mixed with heroin. According to the NCHS, fentanyl and synthetic opioids are blamed for 20,145 of the 64,070 overdose deaths in 2016. Heroin contributed to 15,446 deaths, while prescription opioids caused 14,427.


Potent opioid

Fentanyl (C22H28N20), a lipophilic phenylpiperidine opioid agonist, is generally formulated as a transdermal patch, lollipop and dissolving tablet. Like the opioids derived from opium poppies, such as morphine, fentanyl binds to opioid receptors in the brain and other organs of the body, specifically the mu-receptor.

 opium poppy

Heroin and other opioids come from the opium poppy.  Image: Max Pixel

Such binding mimics the effects of endogenous opiates (endorphins), creating an analgesic effect, as well as a sense of well-being when the chemical binds to receptors in the rewards region in the brain. Drowsiness and respiratory depression are other effects, which can lead to death from an overdose.


Rise of illicit fentanyl

The opioid epidemic can be traced back to the 1990s when pharmaceutical companies began producing a new range of opioid painkillers, including oxycodone, touting them as less prone to abuse. In addition, prescribing rules were relaxed, while advocates championed the right to freedom from pain. Soon, opioids were being prescribed at alarming rates and increasing numbers of patients were becoming hooked.

 

Why is there an opioid crisis? Video: SciShow

Franklin, who was the first person to report in 2006 on the growing death rate from prescribed opioids, says: ‘OxyContin is only a few atoms different to heroin – I call it pharmaceutical heroin.’

A crackdown on prescribing was inevitable. But then, with a shortage of prescription opioids, addicts turned to illicit – and cheaper – heroin. According to Franklin, 60% of heroin users became addicted via a prescribed opioid. ‘You don’t have to take these drugs for very long before it’s very hard to get off,’ he says: ‘Just days to weeks.’ Heroin use soared and with it increased tolerance, leading users to seek out more potent highs. By 2013, there were almost 2m Americans struggling with an opioid-use disorder.


Drugs to fight drugs

 public health emergency

President Trump declared the opioid crisis a public health emergency in October. Image: Pixabay 

Attention is finally being given to the epidemic. US president Donald Trump recently declared a public health emergency, although no new funds will be assigned to deal with the crisis.

There is particular interest around research into a vaccine against fentanyl. Developed by Kim Janda at The Scripps Research Institute, California, US, the vaccine, which has only been tested in rodents, can protect against six different fentanyl analogues, even at lethal doses. ‘What we see with the epidemic, is the need to find alternatives that can work in conjunction with what is used right now,’ he says.

This vaccine could treat heroin addiction. Video: Seeker

The vaccine works by taking advantage of the body’s immune system to block fentanyl from reaching the brain. Its magic ingredient is a molecule that mimics fentanyl’s core structure, meaning the vaccine trains the immune system to recognise the drug and produce antibodies in its presence. These antibodies bind to fentanyl when someone takes the drug, which stops it from reaching the brain and creating the ‘high’.

 

Health & Wellbeing

Around 10 million medical devices are implanted each year into patients, while one-third of patients suffer some complication as a result. Now, researchers in Switzerland have developed a way to protect implants by dressing them in a surgical membrane of cellulose hydrogel to make them more biocompatible with patients’ own tissues and body fluids.  

‘It is more than 60 years since the first medical implant was implanted in humans and no matter how hard we have tried to imitate nature, the body recognises the implant as foreign and tends to initiate a foreign body reaction, which tries to isolate and kill the implant,’ says Simone Bottan at, who leads ETH Zurich spin-off company Hylomorph.

 Hylomorph

Hylomorph is a spin-off company of ETH Zurich, Switzerland. Image: ETH-Bibliothek@Wikimedia Commons

Up to one-fifth of all implanted patients require corrective intervention or implant replacement due toan immune response that wraps the implant in connective tissue (fibrosis), which is also linked with infections and can cause patients pain. Revision surgeries are costly and require lengthy recovery times.

The new membrane is made by growing bacteria in a bioreactor on micro-engineered silicone surfaces, pitted with a hexagonal arrangement of microwells. When imprinted onto the membrane, the microwells impede the formation of layers of fibroblasts and other cells involved in fibrosis.

 pacemaker

25,000 people in the UK have a pacemaker fitted each year. Image: Science Photo Library

The researchers ‘tuned’ the bacteria, Acetobacter xylinum, to produce ca 800 micron-thick membranes of cellulose nanofibrils that surgeons can wrap snuggly around implants. The cellulose membranes led to an 80% reduction of fibrotic tissue thickness in a pig model after six weeks, according to a study currently in press. Results after three and 12 months should be released in January 2018.

It is hoped the technology will receive its first product market authorisation by 2020. First-in-man trials will focus on pacemakers and defibrillators and will be followed by breast reconstruction implants. The strategy will be to coat the implant with a soft cellulose hydrogel, consisting of 98% water and 2% cellulose fibres.  

The membrane will improve the biocompatibility of implants. Video: Wyss Zurich

‘Fibrosis of implantables is a major medical problem,’ notes biomolecular engineer Joshua Doloff at Massachusetts Institute of Technology, adding that many coating technologies are under development.

‘[The claim] that no revision surgery due to fibrosis will be needed is quite a strong claim to make,’ says Doloff, who would also like to see data on the coating’s robustness and longevity.

The silicone topography is designed using standard microfabrication techniques used in the electronics industry, assisted by IBM Research Labs.  

Health & Wellbeing

Often, the pharmaceutical industry is characterised as the ‘bad guy’ of equality in healthcare. This is particularly evident in the United States, with cases such as Martin Shkreli, whose company Turing Pharmaceuticals infamously increased its leading HIV and malaria drug by over 50 times its value overnight, and a lack of regulation in advertising. The latter is accused of influencing prescriptions of certain brands based on consumer demand, which could lead to unnecessary treatment and addiction.

With stories like these dominating the media, it is no wonder the public if often found to harbour a negative view towards ‘Big Pharma’. However, the actions and motives of this industry are rarely fully understood. Here are five facts about pharmaceutical manufacturing you might not know:


1. Out of 5,000-10,000 compounds tested at the pre-clinical stages, only one drug will make it to market

The drug discovery and development process explained. Video: Novartis

This may seem like slim odds, but there are many stages that come before drug approval to make sure the most effective and reliable product can be used to treat patients.

There are four major phases: discovery and development; pre-clinical research,  including mandatory animal testing; clinical research on people/patients to ensure safety; and review, where all submitted evidence is analysed by the appropriate body in hopes of approval.


2. If discovered today, aspirin might not pass current FDA or EMA rules

 older drugs

Some older drugs on the market would not get approval due to safety issues. Image: Public Domain Pictures

Problems with side effects – aspirin is known to cause painful gastrointestinal problems with daily use – mean that some older drugs that remain available might not have gained approval for widespread use today. Both the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) run programmes that monitor adverse side effects in users to keep consumers up-to-date.

Tighter regulation and increased competition mean that the medicines we take today are arguably more effective and safer than ever.


3. The average cost of drug development has increased by a factor of 15 in 40 years

money gif

Originally posted by blisteredblue

Back in the 1970s, the cost to produce a drug from discovery to market was $179 million. Today, drug companies shell out $2.6 billion for the same process – a 1,352% increase! Even considering inflation rates, this number is significantly higher.

With the average length of time needed to develop a drug now 12 years, time is an obvious reason for the high costs. However, the difficulty of finding suitable candidates at the discovery stage is also to blame. Pre-clinical stages can be resource-intensive and time-consuming, making pharmaceutical companies look towards other methods, such as the use of big data.


4. The US accounts for nearly half of pharmaceutical sales

 The Statue of Liberty

The Statue of Liberty. Over 40% of worldwide medicines sales are made by US companies. Image: Wikimedia Commons

The US is the world-leader in pharmaceutical sales, adding $1.2 trillion to the economic output of the US in 2014 and supporting 4.7 million jobs. The country is also home to the top 10 performing pharmaceutical companies, which include Merck, Pfizer, and Johnson & Johnson.

While the EU’s current share is worth 13.5%, this is expected to fall by 2020 with emerging research countries, such as China, projected to edge closer to the US with a share of 25%.


5. Income from blockbuster drugs drives research into rare diseases

 Rare diseases

Rare diseases are less likely to receive investment for pharmaceutical research. Image: Pixabay

Diseases that affect a large proportion of the worldwide population, such as cancer, diabetes, or depression, are able to produce the biggest revenue for pharmaceutical companies due to the sheer volume of demand. But rarer diseases are not forgotten, as research into these illnesses is likely funded by income from widespread use of the aforementioned medicines.

Rare – or ‘orphan’ – diseases are those that affect a small number of the population, or diseases that are more prevalent in the developing world. With the increasing cost of producing a drug, it becomes risky for pharmaceutical companies to create a fairly-priced drug for a small fraction of patients.

However, this seems to be changing. Researchers from Bangor University, UK, found that pharmaceutical companies that market rare disease medicines are five times more profitable than those who do not, and have up to 15% higher market value, which could finally provide a financial incentive for necessary research.

Health & Wellbeing

In recent years, novel innovation in healthcare and pharmaceuticals have hit the headlines with increasing regularity. Each story promises a better quality of life for patients and a product that will ‘revolutionise’ healthcare as we know it. 

However, many of these innovations fail to materialise due to the complexity of the system. Problems with regulation, intellectual property agreements, and manufacturing are just some of the many issues that industry faces when integrating a new product into hospitals and treatment centres.

 Stephen Dorrell

Stephen Dorrell. Image: NHS Confederation@Flickr

So, do we need rethink our expectations of innovation? Speaking at New Scientist Live in September, Stephen Dorrell, Chair of NHS Confederation and a former Health Secretary, said that as an innate characteristic of humans, innovation will not stop. However, we should be more concerned about the difficulty of making good innovation available everywhere and rethinking what we consider the most efficient way of treating patients, he said.

As the most common type of dementia – affecting one in six over the age of 80 – Alzheimer’s disease needs good innovation. With no known cure, current efforts rely heavily on having a care plan once symptoms appear and medications can only slightly improve symptoms for a time as well as slow down the progression of the disease.


Progress in pharmaceuticals 

The Alzheimer’s research community are well versed in the known causes of the disease, with amyloid plaques and tau tangles the most widely accepted causes of the neurodegeneration that leads to Alzheimer’s. As a result, the majority of research and investment in the field is centred around this theory.

Neuro-Bio is a biotechnology start-up that is taking a different approach to making medicines for Alzheimer’s patients. The company is focused on a ‘previously unidentified mechanism’ of the disease that is linked to the development stages of the brain and cell death, and is working on new drug candidates that can stop the peptide involved in this mechanism from functioning improperly in adults.

After a series of setbacks in Alzheimer’s drug development, Prof Margaret Esiri, a neuropathologist at the Nuffield Department of Clinical Sciences, Oxford, said: ‘Neuro-Bio’s approach to the problem of Alzheimer’s disease is novel and scientifically well-founded. It is a good example of the new thinking that is urgently needed in this field’.


Timing it right 

However, with an uncertainty for future success in Alzheimer’s pharmaceuticals, researchers interested in the genetic make-up of neurodegenerative diseases are focusing on how early diagnosis can be beneficial to patients.

 brain matter

Alzheimer’s can cause a significant loss of brain matter (right) compared to a healthy brain (left). Image: National Institutes of Health

According to UCL geneticist John Hardy, a loss in brain matter and amyloid build-up begins 15 to 20 years before symptoms start to appear, highlighting the need for preventative measures. This need is not consistent with what is currently available to patients in the UK however, as to qualify for a clinical trial, patients must be in the advanced stages of Alzheimer’s – often exhibiting severe symptoms that can, quite drastically, negatively affect quality of life for the individual.

Scientists at Case Western Reserve University, Ohio, US, may have solved this issue of early diagnosis after developing a machine learning program that outperforms other methods for diagnosing Alzheimer’s disease. The program integrates known disease indicators and symptoms to predict the likelihood of Alzheimer’s onset. Multiple stage comparisons, which includes associated symptoms that are not always present in Alzheimer’s, allow the program to make a more accurate prediction of who is most vulnerable.

Development of such programs could help initiatives such as the 100,000 Genomes Project which aims to provide the NHS with a new genomic medicine service that can offer better diagnosis and more personalised treatments.  


 Baroness Susan Greenfield

Baroness Susan Greenfield. Image: National Assembly for Wales

Interested in Alzheimer’s disease?

SCI is running a Public Evening Lecture in London on Wednesday 28 February – The 21st Century mind: Blowing it, expanding it, losing itThe talk will be given by Baroness Susan Greenfield, neuroscientist and CEO of Neuro-bio. It is free to attend, but spaces are limited. Don’t miss out – booking opening soon.

Health & Wellbeing

CRISPR/Cas9 is a gene editing tool that is swiftly becoming a revolutionary new technology. It allows researchers to edit the genome of a species by removing, adding or modifying parts of the DNA sequence.

To alter DNA using CRISPR, a pre-designed sequence is added to the DNA using a RNA scaffold (gRNA) that guides the enzyme Cas9 to the section of DNA that scientists want to alter. Cas9 ‘snips’ the selected sequence.

At this point, the cell identifies the DNA as damage and tries to repair it. Using this information, researchers can use repair technology to introduce changes to the genes of the cell, which will lead to a change in a genetic trait, such as the colour of your eyes or the size of a plants leaf.

 Cas9

Cas9 unzips the selected DNA sequence as the latter forms bonds to a new genetic code. Adapted from: McGovern Institute for Brain Research at MIT

Public approval of genetic modification is at an all-time high, with a recent YouGov survey finding only 7% of people in the UK oppose gene editing, although there is still a way to go. Lighter regulation in recent years has allowed smaller companies and academic institutions to undertake research.

The future of farming

One of the industries that has benefited from CRISPR is agriculture. The ongoing GM debate is an example of controversial use of transgenesis, the process of inserting DNA from one species into another, spawning fears of ‘Frankenstein foods’.

Instead of creating mega-crops that out-compete all conventional plants, gene editing provides resistance to harsh environments and infections; particularly significant in the context of global food security.

Disease breakthroughs

Although gene-editing has been a staple of new agriculture technology for many years now, it is only recently that CRISPR has seen successful use in human disease research and resulting clinical trials.

Scientists at the Salk Institute, California, successfully removed the MYBPC3 gene, linked to a common form of heart disease, from a human embryo. The correction was made at the earliest stage of human development, meaning that the condition could not be passed to future generations.

CRISPR is also being used to study embryo development. Recently, scientists at the Francis Crick Institute, London, discovered that the gene OCT4 was vital in these early stages, although its purpose is still not fully understood. Researchers involved believe that more research into OCT4 could help us improve success rates of IVF and understand why some women miscarry.

 A human embryo

A human embryo at day four, taken by a Scanning Electron Microscope. Image: Yorgos Nikas, Wellcome Images

CRISPR is still in the early stages and we are far from editing embryos that can be implanted for pregnancy. Many more safety tests are required before proceeding with any clinical trials, with the next step perhaps replicating the experiment on other mutations such as BRCA1 and BRCA2, the genes responsible for an increased risk of breast cancer.

Experts are confident, however, that this technique could be applied to thousands of other diseases caused by a single mutation, such as cystic fibrosis and ovarian cancers.

The benefits of gene editing are abundant. For example, we may be able to turn the tables on antibiotic-resistant bacteria or ‘super-bugs’ by engineering bacteriophages - viruses that infect bacteria - to target antibiotic resistance genes, knocking them out and allowing conventional antibiotics to work once again. Elsewhere, CRISPR could be used to modify metabolic pathways within algae or corn to produce sustainable and cost-effective ethanol for the biofuel market.

car gif

Originally posted by urbaneway

Is CRISPR ethical?

CRISPR and gene editing will revolutionise many industries, but the fear remains in many that we will slip into a society where ‘designer babies’ become the norm, and individuality will be lost. 

Marcy Darnovsky, Executive Director of the Centre for Genetics and Society, said in a statement: ‘We could all too easily find ourselves in a world where some people’s children are considered biologically superior to the rest of us.’

 superheros

Could CRISPR lead to a new generation of superheros? Image: Cia Gould

Dr Lovell-Badge, from the Francis Crick Institute, disagrees. ‘I personally feel we are duty bound to explore what the technology can do in a safe, reliable manner to help people. If you have a way to help families not have a diseased child, then it would be unethical not to do it,’ he said.

Genetic engineering does not have to have an all-or-nothing approach. There is a middle ground that will benefit everyone with correct regulation and oversight. With its globally renowned research base, the UK government has a great opportunity to encourage genetic experiments and further cement Britain’s place as the genetic research hub of the future.