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.
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.
Organised by the National Human Genome Research Institute each year, National DNA Day in the US on 25 April celebrates the discovery of DNA’s double helix in 1953 and the completion of the Human Genome Project in 2003. Here, we explore the history of DNA and its discovery’s unparalleled effect on science, medicine and the way we now understand the human body.
Discovering DNA’s structure
Using the pictures that she had taken, Franklin was able to calculate the dimensions of the strands and found the phosphates were on the outside of the DNA helix.
Rosalind Franklin working in her lab. Image: Wikimedia Commons
Meanwhile, at the University of Cambridge, James Watson and Francis Crick deduced the double-helix structure of DNA, describing it as ‘two helical chains each coiled round the same axis’ following a right-handed helix containing phosphate diester groups joining β-D-deoxyribofuranose residues with 3’,5’ linkages.
The discoveries made by these scientists would propel the study of genetics into the modern science we know today. Crick and Watson were awarded the Nobel Prize for Physiology or Medicine alongside Maurice Wilkins, who worked with Rosalind Franklin, in 1962. You can read their original paper here.
Dolly the sheep
Dolly on display at the National Museum of Scotland, UK.
Dolly is arguably the most famous sheep in the world, having been the first mammal to be cloned from an adult cell. Born in 1996, Dolly was part of a series of experiments at the Roslin Institute in Edinburgh to create GM livestock that could be used in scientific experiments.
She was cloned using a technique called somatic cell nuclear transfer, where a cell nucleus from one adult is transferred into an unfertilised developing egg cell of another that has had its nucleus removed, which is then implanted into a surrogate mother.
The scientific legacy of Dolly the sheep. Video: Al Jazeera English
Dolly lived until 2003 when she was euthanised after contracting a form of lung cancer. Many speculated that Dolly’s early death was related to the cloning experiment but extensive health screening throughout Dolly’s life by the Roslin Institute suggest otherwise.
Her creation has led to further cloning projects and could be used in the future to preserve the populations of endangered or extinct species, and has led to significant developments in stem cell research.
In 2009, Spanish researchers announced the cloning of a Pyrenean ibex, which has been extinct since 2000, and was the first cloning of an extinct animal. Unfortunately, the ibex died shortly after birth but there have been a few successful stories since then.
The Human Genome Project
Beginning in 1990 and finishing in 2003, the Human Genome Project was an international research initiative that aimed to write the entire sequence of nucleotide base pairs that make up the human genome, including the mapping of all its genes that determine our physical and functional attributes.
The publicly funded $3bn project was able to map 99% of the human genome with 99.99% accuracy, which included its 3.2bn Mega-base pairs, 20,000 genes and 23 chromosome pairs, and has led to advancements in bioinformatics, personalised medicine and a deeper understanding of human evolution.
The US Food and Drug Administration (FDA) has approved Lokelma (sodium zirconium cyclosilicate), formerly ZS-9 – AstraZeneca’s drug for the treatment of adults with hyperkalaemia.
A serious condition, hyperkalaemia is characterised by elevated potassium levels in the blood and can lead to cardiac arrest and death. It is associated with cardiovascular, renal, and metabolic diseases – the risk of hyperkalaemia increases significantly for patients with chronic kidney disease, and those who take common medications for heart failure, such as renin-angiotensin-aldosterone system (RAAS) inhibitors, which can increase potassium in the blood.
To help prevent the recurrence of hyperkalaemia, RAAS-inhibitor therapy is often modified or discontinued, which can compromise its effectiveness and increase the risk of death.
The announcement comes two months after the European Commission granted marketing authorisation for Lokelma in the EU.
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in the fields of oncology, cardiovascular, renal and metabolism, and respiratory.
An innovative new screening method using cell aggregates shaped like spheres may lead to the discovery of smarter cancer drugs, a team from the Scripps Research Institute, California, US, has reported.
The 3D aggregates, called spheroids, can be used to obtain data from potentially thousands of compounds using high throughput screening (HTS). HTS can quickly identify active compounds and genes in a specific biomolecular pathway using robotics and data processing.
A spheroid under a confocal microscope. Image: Kota et al./The Scripps Research Institute
The spheroids – 100 to 600 microns thick in diameter – spread in a similar way to cancer cells in the body and are therefore more effective in identifying potential cancer drugs, the team hypothesises.
For this study, the team focused on KRAS – a gene belonging to the RAS family. It is estimated these genes account for one-third of all cancers.
Robots handle assays in a HTS system. Image: NIH/Flickr
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.