Mosquitoes are a vector of the malarial parasite. Image: Pixabay
There were 219m cases of malaria in 2017, up 2m on the previous year. Increasingly, the disease is drug-resistant and prevention methods are difficult both in non-immune travelers and in areas where the disease is endemic. Moreover, most malaria drugs are designed to reduce symptoms after infection rather than prevent infection or transmission.
New compounds have been discovered with the potential to be novel antimalarial drugs. Image: Pixabay
A team of scientists are working to change that, aiming to treat the malaria parasite at an earlier stage – when it affects the human liver – rather than waiting until the parasite is in the blood. If successful, their work could have a significant impact on global health.
Interested in the pharmaceutical industry and research community? Take a look at this short video to see how we bring science and business together.
Tweaking the chemical structure of the antibiotic vancomycin may offer a new route to tackle the burgeoning problem of antibiotic-resistant bacteria, researchers in Australia have discovered.
Vancomycin has been used since the late 1950s to treat life-threatening infections caused by Gram-positive bacteria, including methicillin-resistant S. aureus (MRSA). The antibiotic works by binding to a precursor of the cell wall component, peptidoglycan, Lipid II, thus inhibiting bacterial growth.
Lipid II is present in both Gram-positive and Gram-negative bacteria. However, in Gram-negative bacteria it is protected by an outer membrane. In Gram-positive bacteria, Lipid II is embedded in the cell membrane but part of the molecule – a pentapeptide component – sticks out, which is what vancomycin binds to.
The researchers at the University of Queensland’s Institute for Molecular Biology (IMB), led by director of superbug solutions Matt Cooper, reasoned that if they could increase the ability of vancomycin to bind to the bacterial membrane, this would make it more difficult for bacteria to develop resistance to it.
‘Our strategy was to add components to vancomycin so that the new derivatives – which we call “vancapticins” – could target more widely the membrane surface,’ explains Mark Blaskovich, senior research chemist at IMB. ‘By providing two binding sites – the membrane surface and the membrane-embedded Lipid II - this allows binding to resistant strains in which the Lipid II has mutated to reduce interactions with vancomycin.’
In addition, the researchers say that the vancapticins have been designed to take advantage of compositional differences between mammalian and bacteria cell membranes – ie bacterial cells have a greater negative charge. The vancapticins have greater selectivity for bacterial cells over mammalian cells, potentially reducing off-target effects and giving a better safety profile. A series of structure–activity studies showed that some of the vancapticins were more than 100 times more active than vancomycin.
Hospital-Associated Methicillin-resistant Staphylococcus aureus (MRSA) Bacteria. Image: NIAID
This membrane-targeting strategy, the researchers say, has the potential to ‘revitalise’ antibiotics that have lost their effectiveness against recalcitrant bacteria as well as enhance the activity of other intravenous-administered drugs that target membrane associated receptors.
John Mann, emeritus professor of chemistry at Queen’s University Belfast, UK, comments: ‘Bacteria have developed numerous strategies to modify the binding, uptake and expulsion of antibiotics, and thus develop resistance. So, it is especially exciting to see the development of these new vancomycin derivatives that enhance the membrane binding properties of the antibiotic, thus enhancing its efficacy and beating the bacteria at their own game.’
A new drug developed by Eli Lilly to combat the symptoms of psoriatic arthritis (PsA) – including severe joint pain and swelling – has been approved for market by the European Commission.
Ixekizumab, or Taltz®, can be used to treat patients with PsA who have not responded to, or are intolerant to, traditional anti-rheumatic drug therapies, such as methotrexate, which act to treat the underlying cause of arthritis to slow disease progression, rather than the symptoms.
PsA is caused by a fault in a person’s immune system, when the body sends out signals for inflammation even when damage has not occurred., causing swollen, stiff, and painful joints. It is a chronic and progressive disease with no known cure.
Vaccines are much debated these days, but before starting a discussion about them, let’s see how a vaccine is defined.
The World Health Organisation defines a vaccine as:
‘a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe, its toxins or one of its surface proteins. The agent stimulates the body’s immune system to recognize the agent as foreign, destroy it, and “remember” it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters.’
We put in our bodies something that looks like or has a tiny part of the ‘microbe’ that produces the disease so that our body can produce the right agents to fight it in case we actually contract the real illness.
A vaccine is comprised of an active ingredient and other added ingredients. Like any other drug, the active ingredient is the key component that triggers the immune response. Beside this, the added ingredients have different roles, such as improving the immune response, or acting as a preservative, stabiliser, or suspending fluid.
These added ingredients are the ones that are sometimes contested due to their toxicity. But when speaking about toxicity, there is a very important point to make. Everything is toxic.
It all comes down to the dose you eat, drink, or otherwise insert into your body. An important indicator of toxicity is LD50 (lethal dose 50), which is the dose at which 50% of individuals die. Sodium chloride, also known as table salt, has a LD50 of 12,400mg/kg (868g of salt for a 70kg individual) for humans. The lower the LD50 indicator is, the more toxic a compound is.
Table salt can also be toxic.
Aluminium salts are used in many vaccines as adjuvants. This means that they help by stimulating the immune response and by a slow release of the active ingredient.
The most used salts are aluminium hydroxide, aluminium phosphate and potassium aluminium sulphate. Data about these compounds are freely accessible by searching for their material safety data sheets (MSDS) on the big chemical suppliers’ websites. The 11th section of an MSDS file is the toxicological information section, which contains the LD50 value, carcinogenicity information, and others.
Section 11 of the aluminium phosphate MSDS Sigma-Aldrich
None of the salts above are reported as carcinogenic, and the LD50 of aluminium phosphate is more than 5,000mg/kg for mice. The total quantity of the aluminium in a vaccine is less 1mg (0.001g), which is a very low quantity. In the normal European diet the amount of aluminium we intake from food varies between 3–10mg a day.
Vaccine composition lists also include compounds and products used in the manufacturing process – even though at the end of manufacture they are present only in trace amounts, if at all.
One of the chemicals on this list that scares people is formaldehyde, which is indeed carcinogenic with and LD50 of 42mg/kg for mice. Nevertheless, the quantity present in a vaccine dose is less 0.1 mg. One 200g pear contains 12mg of formaldehyde. We should always remember ‘the dose makes the poison’, as compound interest illustrates below.
The does makes the poison – ‘toxic’ chemicals in food. Compound Interest
Vaccination is a personal decision. Nevertheless, it should be based on information from multiple verified sources. Easily accessible and clear information can be found on the Vaccine Knowledge Project website designed by the Vaccine Research Group from the University of Oxford.
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
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
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. 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 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.