Symmetry in spectroscopy, reaction mechanisms and bonding Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The importance of symmetry in chemistry Last updated: 02/04/26, 18:25 Published: 08/01/26, 08:00 Symmetry in spectroscopy, reaction mechanisms and bonding Introduction Symmetry is everywhere- in snowflakes, flowers and even art. Chemistry is no different and the symmetrical properties of a molecule often dictate its behaviour. From interpreting spectra, to predicting reaction pathways and understanding bonding, symmetry shapes all chemical disciplines. 1. Symmetry in spectroscopy Firstly, understanding the symmetry of molecules is essential in a range of characterisation techniques. In 1 H NMR spectroscopy, the number of peaks seen in a spectrum correspond to the number of unique chemical environments. For example, dibenzylidene acetone has a plane of symmetry and a rotational axis (C 2 ) through the centre of the carbonyl. This explains why the spectrum only has 5 different proton environments. In IR spectroscopy, infrared radiation is absorbed by a molecule causing stretching and bending of bonds when they vibrate. The total number of vibrational modes can be predicted using: • 3N – 5 rule for linear molecules • 3N – 6 rule for non-linear molecules (where N = no. of atoms) However, only vibrations which cause a change in dipole moment are seen in IR spectra. This explains why CO 2 only shows 3 main absorption peaks, despite having 4 vibrational modes. 2. Symmetry in reaction mechanisms Considering the symmetry of molecules also helps chemists predict the stereochemical outcome of organic reactions. A common example is the E2 elimination of a halogenoalkane, where an alkene is formed via elimination of a halogen. For an E2 elimination to occur, the H and the leaving group must be 180 ° from each other, in an ‘anti-periplanar’ conformation. To predict which groups, have this relationship, Newman projections are used to easily assign and rotate bonds. A Newman projection is a perspective of a molecule, typically by imagining you are looking down a specific C-C bond. See Figure 3 . 3. Symmetry in bonding Lastly, considering the symmetry of a molecule is vital for understanding Molecular Orbital (MO) Theory. MO theory explains how covalent bonding occurs by considering the symmetry elements of the valence orbitals. For example, in H 2 , the two valence 1s orbitals are completely symmetric and therefore can overlap effectively to form a σ molecular orbital. However, in HF, the introduction of 2p orbitals means the shape and symmetry has changed. The 2p x and 2p y orbitals can no longer overlap with the 1s H orbital as their symmetries are incompatible. Using this information, a MO diagram can be constructed to show how the orbitals combine, explaining why H 2 has a single bond. In essence, symmetry determines which orbitals can ‘match up’ to form bonds. See Figure 4 . Conclusion Symmetry influences every aspect of chemistry and is frequently employed to rationalise observed molecular characteristics. While sometimes overlooked, considering the symmetry of a molecule underpins any chemistry undertaken across industry and academia. If you enjoyed this article, future articles could build on this topic by introducing Group Theory and showing how you can predict an entire vibrational spectrum, or the molecular geometry of a compound based entirely on its symmetry. Written by Antony Lee Related article: Diels-Alder reaction REFERENCES S. Civis, M. Ferus, A. Knizek, in The Chemistry of CO 2 and TiO 2 : From Breathing Minerals to Life on Mars, ed. S. Civis, M. Ferus, A. Knizek, Springer Nature, Switzerland, 1 st edn., 2019, vol. 1, ch. 1, pp. 1-7 A. Burrows, J. Holman, S. Lancatser, T. Overton, A. Parsons, G. Pilling, G. Price, in Chemistry 3 , Oxford University Press, Oxford, 3 rd edn., 2017, ch.4, pp. 172-219 Project Gallery

Trigeminal neuralgia is a chronic disorder that affects the trigeminal nerve- responsible for facial sensation Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link What a new study says about smoking and trigeminal neuralgia Last updated: 04/05/26, 18:50 Published: 07/05/26, 08:00 Trigeminal neuralgia is a chronic disorder that affects the trigeminal nerve- responsible for facial sensation Smoking is the act of inhaling and exhaling smoke from burning tobacco, exposing the body to nicotine and a wide range of harmful chemicals. It is widely recognised as a leading cause of serious health conditions such as heart disease, cancer, and respiratory illness, but its effects extend beyond these well-known risks. Smoking can also influence the nervous system and the function of blood vessels, potentially altering how pain is triggered and experienced within the body. One condition where this interaction may be particularly significant is trigeminal neuralgia, a chronic disorder that affects the trigeminal nerve- cranial nerve V- (as depicted in Figure 1 ) responsible for facial sensation. This condition is characterised by sudden, intense bursts of facial pain, often described as an electric shock, which can be triggered by simple everyday actions such as speaking, eating, or even a light touch. Together, these factors highlight a possible and important link between smoking and the development or severity of trigeminal neuralgia. Recent research has begun to uncover this connection in more detail, offering new insights into how smoking may shape the course of the condition. In patients undergoing microvascular decompression surgery, smokers were found to develop trigeminal neuralgia at a younger age than non-smokers and were more likely to experience pain across multiple branches of the nerve. This suggests a broader spread of symptoms and potentially a more complex form of the disorder. Outcomes after surgery also appeared to differ, with smokers less likely to remain free from pain in the long term without medication. However, an encouraging finding emerged for those who had stopped smoking at least six months before surgery, as their recovery resembled that of individuals who had never smoked. This raises the possibility that quitting smoking could meaningfully improve treatment outcomes. The reasons behind these patterns are likely to be multifaceted, involving both behavioural and biological influences. Smoking increases the frequency of oral movements, which may trigger pain episodes more often in people with trigeminal neuralgia. At the same time, it is known to affect the structure and function of blood vessels in the brain and may alter the protective covering of nerves, making them more sensitive to pressure or irritation. Although visible nerve compression did not differ greatly between smokers and non-smokers, subtle changes at a microscopic level could still intensify symptoms and limit recovery. Age also appears to play an important role, as younger patients tend to have poorer surgical outcomes, and smokers in the study were generally younger at the onset of symptoms. Altogether, these findings paint a compelling picture of how smoking may not only contribute to the earlier development of trigeminal neuralgia but also influence its severity and response to treatment, reinforcing the value of smoking cessation as part of patient care. Written by Maria Kahloon Related articles: Genes related to excessive smoking / Smoking cessation Project Gallery

Exenatide as a potential drug Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link A common diabetes drug treating Parkinson’s disease 05/04/26, 15:28 Last updated: Published: 24/01/24, 21:15 Exenatide as a potential drug Disclaimer: the results from the February 2025 Phase 3 Exenatide-PD3 trial shows that exanetide did not outperform the placebo, and did not slow the progression of Parkinson's disease. Parkinson's (PD) is the second most common neurodegenerative disorder. The connection between type 2 diabetes (T2DM) and PD was discovered in 1993, when PD patients with co-existing T2DM had worse motor symptoms and response to therapy. Dopaminergic neurons promote eating behaviour in hypoglycaemic states, mediated via insulin receptors in the substantia nigra, because dopaminergic neuronal loss affects glycaemic control. Thus, T2DM patients are more likely to acquire PD than people without diabetes. Excess glucose in the brain, as found in uncontrolled T2DM, may interact randomly with surrounding proteins and interfere with their function. These interactions also result in toxic end products promoting inflammation and α-synuclein clustering, both of which are PD characteristics. Over a 12-year period, retrospective data (N=8,190,323) showed that T2DM responders had considerably greater PD rates when compared to those without diabetes. The rise was significantly more pronounced among individuals with complex T2DM and those aged 25-44. Exenatide: Overview and Mechanism of Action Exenatide is a synthetic form of exendin-4, a naturally occurring protein identified in the saliva of the Gila monster (poisonous lizard endemic to the Southwest US) by Dr. Eng in the early 1990s. In humans, the chemical is produced after a meal to increase insulin production, decreasing blood sugar. GLP-1 degrades fast in humans, and its benefits are short-lived. However, investigations have shown effects of exendin-4 continue longer in people. This finally led to FDA clearance in 2005, when the product was sold as Byetta TM . Its current indications are for the treatment of balancing glucose levels in T2DM with or without additional oral hypoglycemic medications. This glycaemic control is an analogue of human GLP-1, used in T2DM treatment, either alone or in conjunction with other antidiabetic medications. Exendin-4's neuroprotective characteristics may aid in rescuing degenerating cells and neuron protection. Because T2DM and PD are linked, researchers want to explore its effectiveness as a PD therapy. Patients treated with exenatide for one year (in addition to standard medication) experienced less deterioration in motor symptoms when tested without medication compared to the control group. Research on Exenatide as a Potential Parkinson's Disease Therapy 21 patients with intermediate PD were assessed over a 14-month period, and their progress was compared to 24 other people with Parkinson's who served as controls. Exenatide was well accepted by participants, albeit some individuals complained about weight loss. Significantly, exenatide-treated participants improved their PD movement symptoms, while the control patients continued to deteriorate. The researchers investigate exenatide, a possible PD therapy, in an upcoming clinical study, lending support to the repurposing of diabetes drugs for Parkinson's patients. This research adds to the evidence for a phase 3 clinical trial of exenatide for PD patients. Data on 100,288 T2DM revealed that people using two types of diabetic medications, GLP-1 agonists and DPP4-inhibitors, were less likely to be diagnosed with Parkinson's up to 3.3 years follow-up. Those who used GLP-1 agonists were 60% less likely to acquire PD than those who did not. The results revealed that T2DM had a higher risk of Parkinson's than those without diabetes, although routinely given medicines, GLP-1 agonists, and DPP4-inhibitors seemed to reverse the association. Furthermore, a 2-year follow-up research indicated individuals previously exposed to exenatide displayed a substantial improvement in their motor characteristics 12 months after they ceased taking the medication. However, this experiment was an open-label research so the gains may be explained by a placebo effect. The research adds to the evidence that exenatide may assist to prevent or treat PD, perhaps by altering the course of the illness rather than just lowering symptoms. Other risk factors for PD should be considered by clinicians when prescribing T2DM drugs, although further study is required to clarify clinical significance. Findings from Clinical Trials and Studies Based on these findings, the UCL team broadened their investigation and conducted a more extensive, double-blind, placebo-controlled experiment. The findings establish the groundwork for a new generation of PD medicines, but they also confirm the repurposing of a commercially existing therapy for this illness. Patients were randomly randomised (1:1) to receive exenatide 2 mg or placebo subcutaneous injections once weekly in addition to their current medication for 48 weeks, followed by a 12-week washout period. Web-based randomisation was used, with a two-stratum block design depending on illness severity. Treatment allocation was concealed from both patients and investigators. The main outcome was the adjusted difference in the motor subscale of the Movement Disorders Society Unified Parkinson's Disease Rating Scale after 60 weeks in the realistically defined off-medication condition. Six major adverse events occurred in the exenatide group and two in the placebo group, but none were deemed to be connected to the research treatments in either group. It is unclear if exenatide alters the underlying illness mechanism or causes long-term clinical consequences. Implications and Future Directions Indeed, the UCL study showed that exenatide decreases deterioration compared to a placebo. However, participants reported no change in their quality of life. The study team would broaden their study to include a broader sample of people from several locations. Because PD proceeds slowly, longer-term trials might provide a better understanding of how exenatide works in these responders. Overall, findings suggest that gathering data on this class of medications should be the topic of additional inquiry to evaluate their potential. Exenatide is also being studied to see whether it might postpone the onset of levodopa-induced problems (e.g., dyskinesias). Furthermore, if exenatide works for Parkinson's, why not for other neurodegenerative illnesses (Alzheimer's, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis) or neurological diseases (including cerebrovascular disorders, traumatic brain injury...)? Exenatide has been FDA-approved for diabetes for many years and has a good track record, but it does have some adverse side effects in Parkinson's patients, namely gastrointestinal difficulties (nausea, constipation). Exenatide as a prospective PD therapy is an example of medication repurposing or repositioning, an essential method for bringing novel therapies to patients in a timely and cost-effectively. However, further research is required, so it will be many years before a new therapy is licenced and available. Drug repurposing, or using authorised medicines for one ailment to treat another, opens up new paths for Parkinson's therapeutic development. Conclusion Exenatide shows potential as a therapy for Parkinson's disease (PD). Studies have shown that exenatide may help improve motor symptoms and slow down the progression of PD. However, further research and clinical trials are needed to fully understand its effectiveness and long-term effects. The findings also suggest that repurposing existing medications, like exenatide, could provide new avenues for developing PD therapies. While exenatide shows promise, it will likely be many years before it is licensed and widely available as a PD treatment. PROJECT GALLERY IMAGES DESCRIPTION Figure 1- The use of GLP-1 is beyond diabetes treatment. Nineteen clinical studies found that GLP-1 agonists can improve motor scores in Parkinson's Disease, improve glucose metabolism in Alzheimer's, and improve quality of. They can also treat chemical dependency, improve lipotoxicity, and reduce insulin resistance. However, adverse effects are primarily gastrointestinal. Thus, GLP-1 analogues may be beneficial for other conditions beyond diabetes and obesity. Figure 2- Potent GLP-1 agonists suppress appetite through a variety of mechanisms, including delayed gastric emptying, increased glucose-dependent insulin secretion, decreased glucagon levels, and decreased food ingestion via central nervous system effects. Short-acting agents, including exenatide, primarily function by impeding gastric evacuation, thereby leading to a decrease in postprandial glucose levels. On the contrary, extended-release exenatide and other long-acting agonists (e.g., albiglutide, dulaglutide) exert a more pronounced impact on fasting glucose levels reduction via their mechanism of action involving the release of insulin and glucagon. The ineffectiveness of long-acting GLP-1 receptor agonists on gastric evacuation can be attributed to the development of tolerance to GLP-1 effects, which is regulated by parasympathetic tone alterations. Figure 3- Illustrated is the cross-communication with insulin receptor signalling pathways and downstream effectors . Biomarkers can be derived from the formation and origin of extracellular vesicles, which indicate the initial inward budding of the plasma membrane. An early endosome is formed when this membrane fuses; it subsequently accumulates cytoplasmic molecules. As a consequence, multivesicular bodies are generated, which subsequently fuse with the plasma membrane and discharge their constituents into the extracellular milieu. Akt denotes protein kinase B; Bcl-2 signifies extracellular signal-related kinase; Bcl-2 antagonist of death; Bcl-2 extra large; Bcl-XL signifies Bcl-2; Bim signifies Bcl-2-like protein 11; cAMP signifies cyclic adenosine monophosphate; CREB signifies cAMP response element-binding protein; Erk1/2 signifies extracellular signal-related kinase IDE, insulin-degrading enzyme; IL-1α, interleukin 1α; IRS-1, insulin receptor signalling substrate 1; MAPK, mitogen-associated protein kinase; mTOR, mechanistic target of rapamycin; mTORC1, mTOR complex 1; mTORC2, mTOR complex 2; NF-kB, nuclear factor–κB; PI3-K, phosphoinositide 3-kinase; PKA, protein kinase; FoxO1/O3, forkhead box O1/O3, forkhead box O1/O3; GRB2, growth factor receptor-bound protein 2; GSK-3β, Written by Sara Maria Majernikova Related articles: Pre-diabetes / Will diabetes mellitus become an epidemic? / Parkinson's risk / Markers for Parkinsonism Project Gallery

Many commercial activities are negative, particularly the production and marketing of ultra-processed foods (UPFs), which have contributed to a global obesity crisis. Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Dessert deception: how junk food advertising affects public health Last updated: 29/05/26, 18:22 Published: 04/06/26, 08:00 Many commercial activities are negative, particularly the production and marketing of ultra-processed foods (UPFs), which have contributed to a global obesity crisis. Introduction Chocolate. Crisps. Popcorn. If you're living in the UK, these are things you will no longer see on TV before 9 pm and in paid-for online advertising. This is because the UK has recently implemented a landmark ban on junk food advertisements, with the aim of making unhealthy food less desirable and therefore less consumed by the public. However, research from the World Health Organisation (WHO) suggests that marketing restrictions are only one small part of a strategy to combat the global rise in obesity. Unfortunately, eating habits are no longer just a matter of individual choice: they are increasingly being affected by commercial determinants of health. Researchers have defined them as "strategies and approaches used by the private sector to promote products and choices that are detrimental to health". While some commercial activities can be positive, many are negative, particularly the production and marketing of ultra-processed foods (UPFs), which have contributed to an obesity crisis globally. Frontier Economics calculated the cost of obesity to be approximately £74 billion a year for the UK in an analysis for the Tony Blair Institute, of which the cost to the NHS is more than £11 billion. The science of "engineered" cravings A review from Harvard, Michigan, and Duke University suggests that many UPFs share more characteristics with tobacco cigarettes than with natural foods like fruit or vegetables. The research identified some key strategies used by both the food and tobacco industries to drive addiction and compulsive consumption. They are "dose optimisation", "speed of delivery", "hedonic engineering" and "deceptive reformulation", seen in Table 1 . Table 1 - A comparison of key strategies used by both the food and tobacco industries to drive addiction and compulsive consumption. Source: https://onlinelibrary.wiley.com/doi/10.1111/1468-0009.70066 Strategy UPFs (ultra-processed foods) Cigarettes Dose optimisation UPFs are calibrated to hit a "hedonic sweet spot" of refined carbohydrates and added fats that maximise reward without causing aversion. Nicotine dose is standardised in cigarettes that maximise reward without causing aversion. Speed of delivery Processing techniques break down the food matrix, stripping away fibre and protein so that carbohydrates, sugar and added fats are instantly absorbed into the bloodstream. Additives are used to further increase the absorption speed and efficiency. This rapid delivery triggers a sharper dopamine surge in the brain's reward pathways, increasing the potential for addiction. Industrial processing breaks down the tobacco plant matrix, making it easy to rapidly absorb nicotine through inhalation, with additives added to increase nicotine's speed of delivery. Hedonic engineering Companies add artificial flavours, sweeteners, colourants and more to create "flavour bursts" that fade quickly, intentionally added to encourage repeated intake and amplify appeal. Cigarettes contain flavourings, menthol, and sweeteners for the same reason. Deceptive reformulation UPFs are marketed using "health-washing" claims and terms like "lighter", "low-fat", "sugar-free" and "vitamin-enhanced" to deflect regulation while maintaining addictive properties. Companies market "light" cigarettes and filters as being safer, even though they are still addictive. The UK's landmark 2026 junk food advertising ban On 5 January 2026, the UK implemented a nationwide ban on television and online advertisements for products high in fat, salt, and sugar (HFSS). This ban prohibits junk food ads on TV before the 9 pm watershed and imposes a total ban on paid-for online advertising. The legislation targets the most vulnerable demographic: children, whose developing dietary habits are easily manipulated by high-energy and colourful branding. The UK government expects this action to remove up to 7.2 billion calories from UK children's diets every year, reduce the number of children living with obesity by 20,000 and deliver approximately £2 billion in health benefits over time. The ban is supported by evidence from the National Child Measurement Programme's annual report for the academic year 2024/2025 , which shows that at the start of primary school, approximately 10% of children in England are already living with obesity. This figure rises to more than 22% by the time children leave primary school, as seen in Figure 1 . However, while public health experts have said that the ban is "long overdue", they warn that industry loopholes are undermining its effectiveness. In the UK, while specific products like pizzas or burgers are banned, the "brand-only" exemption allows companies to advertise their brand (e.g., the McDonald's "Golden Arches") as long as specific HFSS products aren't shown. This has led to a shift in marketing strategy: research from the Food Foundation shows that food companies increased their outdoor advertising spend, including billboards and public transport, by 28% between 2021 and 2024. Examples can be seen in Figure 2a and Figure 2b . McDonald's alone has spent £86 million on outdoor ads in 2024, up 71% since 2021, according to the Health Foundation . The WHO's perspective on why pricing matters While the UK focuses on advertising, the WHO warns that harmful products are becoming cheaper globally. Recent WHO reports reveal that weak tax systems are failing to keep pace with inflation and income growth, making sugary drinks and alcohol more affordable than they were years ago. Due to this, the WHO advocates for health taxes as one of the strongest tools for promoting well-being. Dr Tedros Adhanom Ghebreyesus, WHO Director-General, explains that "health taxes are one of the strongest tools we have for promoting health and preventing disease". In the UK, the 2018 Soft Drinks Industry Levy is cited as a major success; it generated £338 million in revenue in 2024 and has been associated with lower obesity rates in girls, particularly in deprived areas. However, the WHO notes that globally, sugary drink taxes often account for only 2% of the retail price, which is far too low to be effective compared to the 50-60% tax rates seen on tobacco. To address this, the WHO launched the "3 by 35" initiative , aiming to significantly increase the real prices of tobacco, alcohol, and sugary drinks by at least 50% by 2035 through tax increases. The economic win Contrary to industry arguments that these restrictions harm the economy, new research from the Sheffield Addictions Research Group suggests that reducing consumption of unhealthy products is actually a net economic gain for the UK. Because money spent on local services stays in the UK and money spent on global junk food brands often goes to the companies, reallocating just 10% of spending from confectionery to other domestic sectors could boost the UK economy by £389 million and create nearly 7,000 new jobs. Conclusion The UK's 2026 ban on junk food adverts is a significant step towards holding the food industry accountable. However, this must be seen as the first of many steps, rather than a final solution. While the ban restricts TV and online ads, industry giants are already exploiting loopholes to maintain their influence over people's food preferences, especially children's. To achieve its ambition of raising the healthiest generation of children ever, the UK must acknowledge that many UPFs are not just poor dietary choices but industrially engineered substances designed to influence human biology and drive compulsive consumption, much like tobacco. A truly effective strategy requires a whole systems approach that moves beyond individual responsibility to food industry accountability. This includes closing loopholes in outdoor advertising and sports sponsorship, and implementing health taxes aligned with the WHO's "3 by 35" initiative that rise with inflation to ensure harmful products do not become more affordable over time. Instead of harming finances, this shift is actually a significant economic win. This means transitioning from a model of "treating sickness" to one of active prevention is not just a public health imperative; it is also a strategic investment in the country's long-term economic and social prosperity. Written by Naoshin Haque Related articles: Rising food prices / Food at the molecular level / Childhood obesity Project Gallery

What my role entails Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Exploring My Role as a Clinical Computer Scientist in the NHS 17/04/25, 11:23 Last updated: Published: 06/05/24, 14:03 What my role entails When we think about career choices, we’re often presented with singular choices. Clinical Scientific Computing is a field that combines healthcare and computing. Despite it being relatively unknown, it is an important cog in the healthcare machine. When I applied for the Scientific Training Program in 2021, the specialism I applied for (Clinical Scientific Computing) had one of the lowest application rates out of approximately 27 specialisms. Awareness of this area has now improved, both thanks to better advertisement and exponential advancements in technology and healthcare. According to the NHS, there are now 26.8 thousand full-time equivalent healthcare scientists in England's NHS. As a clinical computer scientist, one's expertise can be applied in diverse settings, including medical physics laboratories and clinical engineering departments. My role in radiotherapy involves overseeing the technical aspects of clinical workflows, ensuring the seamless integration of technology in patient care. Training is a crucial part of being a proficient computer scientist. Especially with the growth of scientific fields in the NHS, there's always an influx of juniors and trainees, and that in turn, warrants the need for excellent trainers. A clinical scientist is someone who is proficient in their craft and able to explain complex concepts in layman's terms. As Einstein famously said: If you can't explain it to a 6-year-old, you can't understand it yourself. Although I am still technically a trainee, I am expected to partake in the training of the more junior trainees in my schedule. On a typical day, this may be as simple as explaining a program and demonstrating its application, or I may dismantle a PC and go through each component, one by one. At the core of clinical science is research. You won't go a day without working on at least one project and sometimes these may not even be your own. Collaboration with others is a huge part of the job. Every scientist has a different way of thinking about a problem, and this is exactly what keeps the wheels spinning in a scientific department. There are numerous times when I seek the help of others and vice versa. It is difficult to talk about 'typical' projects because they are often so varied in scientific computing, but it is likely that you will find yourself working on a variety of programming tasks. Having clinical know-how is crucial when working on projects in this field, and that aspect is exactly what separates the average computer scientist from the clinical computer scientist. A project I am currently working on involves radiation dose calculations, which naturally involves understanding the biological effects of radiation on the human body. This isn't a typical software development project so having a passion for healthcare is absolutely necessary. The unpredictability of technology means that troubleshooting is a constant aspect of our work. If something goes wrong in the department (which it often does), it is our responsibility as technical experts to quickly but effectively diagnose and fix the problems. The clinical workflow is highly sensitive in healthcare especially the cancer pathway where every minute counts. If a radiographer is unable to access patient records or there is an error with a planning system, this can have detrimental effects on the quality of patient care. Addressing errors, like those in treatment planning systems, necessitates a meticulous approach to diagnosis, often leading us from error code troubleshooting to on-site interventions. For example, I may be required to physically attend a treatment planning room and resolve an issue with the PC. This narrative offers a glimpse into the day-to-day life of a clinical computer scientist in the NHS, highlighting the critical blend of technical skill, continuous learning, and the profound impact on patient care. Through this lens, we can hopefully appreciate the essential role of clinical scientific computing in advancing healthcare, marked by innovation, collaboration, and a commitment to improving patient outcomes. This narrative offers a glimpse into the day-to-day life of a clinical computer scientist in the NHS, highlighting the critical blend of technical skill, continuous learning, and the profound impact on patient care. Through this lens, we can hopefully appreciate the essential role of clinical scientific computing in advancing healthcare, marked by innovation, collaboration, and a commitment to improving patient outcomes. For more information on this specialism . Written by Jaspreet Mann Related articles: Virtual reality in healthcare / Imposter syndrome in STEM Project Gallery

Vicuñas are members of the camelid family Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The cost of coats: celebrating 55 years of vicuña conservation 08/03/26, 18:25 Last updated: Published: 09/10/24, 15:03 Vicuñas are members of the camelid family This is article no. 1 in a series on animal conservation. Next article: Conserving the California condor . Is the softest coat in the world worth the near-extinction of a species? Just ask a vicuña, the wild cousin of llamas and alpacas. After being widely hunted in South America in the mid-20th century, the vicuña population thrives. Their recovery is considered one of the earliest successes in modern wildlife conservation, setting a precedent for sustainable development. October 2024 marked the 55th anniversary of the first international agreement to conserve these furry friends. In its honour, here is the story of vicuña conservation. What are vicuñas? Vicuñas have a unique biology. They are members of the camelid family ー which includes llamas, alpacas, and camels. Vicuñas live in high-altitude arid grasslands in South America (Figure 1). Their families consist of one alpha male, multiple females, and their offspring – while bachelor males form their own groups. Unlike other camelids, vicuña families remain together for most of the year. Vicuñas are herbivores with characteristic grazing and defecating behaviours that shape the surrounding plant community. Therefore, their ecological role cannot be underestimated. How vicuñas nearly went extinct However, vicuñas are hunted by humans because their wool is the finest and softest in the world. They are difficult to domesticate, and their habitat has no hiding spots, so they are easy poaching targets. Their intricate social structure means killing one vicuña has unforeseen impacts on the rest of the population. Consequently, expensive wool comes at the expense of a fascinating species. Demand for ultra-fine vicuña wool made hunting the animals a lucrative business in South America. Although 15th-16th century Inca rulers wore high-end clothing made from vicuña wool, it was usually harvested without killing the animals. European colonisation in the 19th-20th centuries opened vicuña wool to a wealthy international market, making poaching more popular and reckless than under Inca rule. These inconsiderate hunting practices continued after South American countries gained independence. As the luxurious wool remained in demand, the vicuña population decreased by over 99% between 1940 and 1965. Conservation policies saved the vicuñas South American national governments soon realised that indiscriminate vicuña hunting had to stop. As well as being ecologically important, vicuñas should not be allowed to go extinct because of their economic value. Peru had the largest proportion of the vicuña population, so in 1966 its government set up a nature reserve called Pampa Galeras. Creating this reserve involved negotiating with rural communities so that both people and vicuñas benefitted, for example, by employing locals at the reserve. This was one of the earliest examples of what is now known as sustainable development, which provides rural communities with a way of life that works alongside ecosystems rather than damaging them. Scientists found that vicuñas changed their social structures inside Pampa Galeras to maximise reproductive success. A 1987 study suggested that because females had more time to graze without the constant threat of predators and poachers, their reproductive success was higher. The creation of this reserve was the first of many successful steps South America took in the 1960s towards vicuña recovery. In October 1969, Argentina, Chile, Ecuador, and Bolivia joined Peru in the efforts to conserve vicuñas. Their Convention for the Conservation of the Vicuña banned international trade and massively restricted hunting. Since the convention successfully led to a rise in vicuña numbers, it was modified in 1979 so that sustainable vicuña wool could be sold. Meanwhile, conservation laws were being established in the United States and European Union, the wildlife trade regulator CITES was established, and public awareness about the biodiversity crisis was rising. This international effort saved vicuñas from extinction, and today there are 350,000 to 500,000 of them ( Figure 2 ). Although governments have played a huge role in conserving the vicuña, local communities have also contributed. People in Chile and Peru have revived the non-lethal, Inca traditional way of shearing vicuña to harvest their wool. This has many benefits: locals are de-colonising their culture and re-connecting with their heritage, the wool provides a source of income, and the vicuña population remains stable. Vicuñas were classified as ‘least concern’ for conservation by the International Union for Conservation of Nature in 2018. Climate change, mite infestations, and competition with livestock are affecting the population today – but to a much smaller extent than poaching was. Thus, vicuñas are back to freely roaming the Andes. Conclusion Conserving the vicuña relied on political willpower and community involvement. In the 55+ years since, ecologists have used this charismatic and distinctive animal to galvanise wildlife conservation worldwide. The vicuña’s story should also remind us that what we wear has financial and ecological costs. Written by Simran Patel Related articles: Conservation of marine igunanas / Gal á gapos tortoises REFERENCES Acebes, P., Wheeler, J., Baldo, J.L., Tuppia, P., Lichtenstein, G., Hoces, D. & Franklin, W.L. (2018) Vicuna: Vicugna vicugna . The IUCN Red List of Threatened Species 2018 . Available from: https://ri.conicet.gov.ar/handle/11336/178499 (Accessed 12th September 2024). Bosch, P.C. & Svendsen, G.E. (1987) Behavior of Male and Female Vicuna (Vicugna vicugna Molina 1782) as It Relates to Reproductive Effort. Journal of Mammalogy . 68 (2): 425–429. Available from: https://doi.org/10.2307/1381491 (Accessed 23rd September 2024). González, B. et al. (2019) Phylogeography and Population Genetics of Vicugna vicugna : Evolution in the Arid Andean High Plateau. Frontiers in Genetics . 10. Available from: https://doi.org/10.3389/fgene.2019.00445 (Accessed 22nd September 2024). Karandikar, H., Donadio, E., Smith, J.A., Bidder, O.R. & Middleton, A.D. (2023) Spatial ecology of the Vicuña ( Lama vicugna ) in a high Andean protected area. Journal of Mammalogy . 104 (3): 509–518. Available from: https://doi.org/10.1093/jmammal/gyad018 (Accessed 11th September 2024). Lyster, S. (1985) VICUNA. In: International Wildlife Law: An Analysis of International Treaties concerned with the Conservation of Wildlife . Cambridge: Cambridge University Press: 88–94. Nolan, D. (2025) How an Ancestral Peruvian Ceremony Is Saving the Once-Endangered Vicuña . Smithsonian Magazine . Available at: https://www.smithsonianmag.com/travel/how-an-ancestral-peruvian-ceremony-is-saving-the-once-endangered-vicuna-180986933/ (Accessed: 7 March 2026). Reider, K.E. & Schmidt, S.K. (2021) Vicuña dung gardens at the edge of the cryosphere. Ecology . 102 (2): 1–3. Available from: https://www.jstor.org/stable/26998110 (Accessed 11th September 2024). UNESCO (2024) Ancestral practice promotes vicuña conservation and sustainable . unesco.org . Available at: https://www.unesco.org/en/articles/ancestral-practice-promotes-vicuna-conservation-and-sustainable-development-chiles-lauca-biosphere (Accessed: 7 March 2026). Vilá, B. & Arzamendia, Y. (2022) Weaving a vicuña shawl. Pastoralism . 12 (1): 46. Available from: https://doi.org/10.1186/s13570-022-00260-6 (Accessed 11th September 2024). Wakild, E. (2020) Saving the Vicuña: The Political, Biophysical, and Cultural History of Wild Animal Conservation in Peru, 1964–2000. The American Historical Review . 125 (1): 54–88. Available from: https://doi.org/10.1093/ahr/rhz939 (Accessed 11th September 2024). Yacobaccio, H. (2009) The Historical Relationship Between People and the Vicuña. In: Gordon, I.J., ed. The Vicuña: The Theory and Practice of Community Based Wildlife Management . Boston, MA: Springer US: 7–20. Project Gallery

Nanoparticles have unique properties Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Nanoparticles: the future of diabetes treatment? 17/07/25, 11:52 Last updated: Published: 06/05/24, 14:20 Nanoparticles have unique properties Diabetes mellitus is a chronic metabolic disorder affecting millions worldwide. Given its myriad challenges, there is a substantial demand for innovative therapeutic strategies in its treatment. The global diabetic population is expected to increase to 439 million by 2030, which will impose a significant burden on healthcare systems. Diabetes occurs when the body cannot produce enough insulin, a hormone crucial for regulating glucose levels in the blood. This deficiency leads to increased glucose levels, causing long-term damage to organs such as the eyes, kidneys, heart, and nervous system, due to defects in insulin function and secretion. Nanoparticles have unique properties making them versatile in their applications and are promising to help revolutionise the future of the treatment of diabetes. This article will explore the potential of this emerging technology in medicine and will address the complexities and issues that arise with the management of diabetes. Nanoparticles have distinct advantages: biocompatibility, bioavailability, targeting efficiency and minimal toxicity, making them ideal for antidiabetic treatment. The drug delivery is targeted, making the delivery precise and efficient, avoiding off-target effects. Modifying nanoparticle surfaces enhances therapeutic efficacy, enabling targeted delivery to specific tissues and cells, while reducing systemic side effects. Another currently researched key benefit is real-time glucose sensing and monitoring, which addresses a critical aspect in managing diabetes, as nanoparticle-based glucose sensors can detect glucose levels with high sensitivity and selectivity. This avoids the use of invasive blood sampling and allows for continuous monitoring of glucose levels. These can be functionalised and integrated into wearable devices, or implanted sensors, making it convenient and reliable to monitor and to be able to optimum insulin therapy. Moreover, nanoparticle-based approaches show potential in tissue regeneration, aiding insulin production restoration. For example, in particular, nanomedicine is a promising tool in theranostics of chronic kidney disease (CKD), where one radioactive drug can diagnose and a second delivers the therapy. The conventional procedure to assess renal fibrosis is by taking a kidney biopsy, which is then followed by a histopathological assessment. This method is risky, invasive, and subjective, and less than 0.01 % of kidney tissue is examined which results in diagnostic errors, limiting the accuracy of the current screening method. The standard use of pharmaceuticals has been promising but can cause hypoglycaemia, diuresis, and malnutrition because of the low caloric intake. Nanoparticles offer a new approach to both diagnosis and treatment and are an attractive candidate for managing CKD as they can carry drugs and enhance image contrast, controlling the rate and location of drug release. In the treatment of this multifaceted disease, nanoparticle delivery systems seem to be a promising and innovative therapeutic strategy, with the variety in the methods of delivery. The range of solutions that are currently being developed are promising, from enhancing the drug delivery to monitoring the glucose level, to direct tissue regeneration. There is immense potential for the advancement of nanomedicines, helping improve patient outcomes, the treatment efficacy, and allowing the alleviation of the burden and side effects of the disorder. With ongoing efforts and innovation, the future treatment of diabetes can be greatly helped with the use of nanoparticles, and these advancements will improve strategies for the management and future treatment of diabetes. Written by Saanchi Agarwal Related articles: Pre-diabetes / Can diabetes mellitus become an epidemic? / Nanomedicine / Nanoparticles on gut health / Nanogels / Nanocarriers REFERENCES Lemmerman LR, Das D, Higuita-Castro N, Mirmira RG, Gallego-Perez D. Nanomedicine-Based Strategies for Diabetes: Diagnostics, Monitoring, and Treatment. Trends Endocrinol Metab. 2020 Jun;31(6):448-458. doi: 10.1016/j.tem.2020.02.001. Epub 2020 Mar 4. PMID: 32396845; PMCID: PMC7987328. Dehghani P, Rad ME, Zarepour A, Sivakumar PM, Zarrabi A. An Insight into the Polymeric Nanoparticles Applications in Diabetes Diagnosis and Treatment. Mini Rev Med Chem. 2023;23(2):192-216. doi: 10.2174/1389557521666211116123002. PMID: 34784864. Luo XM, Yan C, Feng YM. Nanomedicine for the treatment of diabetes-associated cardiovascular diseases and fibrosis. Adv Drug Deliv Rev. 2021 May;172:234-248. doi: 10.1016/j.addr.2021.01.004. Epub 2021 Jan 5. PMID: 33417981. L. Tillman, T. A. Tabish, N. Kamaly, A. El-Briri F, C. Thiemermann, Z. I. Pranjol and M. M. Yaqoob, Review Advancements in nanomedicines for the detection and treatment of diabetic kidney disease, Biomaterials and Biosystems, 2022, 6, 100047. J. I. Cutler, E. Auyeung and C. A. Mirkin, Spherical nucleic acids, J Am Chem Soc, 2012, 134, 1376–1391. Veiseh, O., Tang, B., Whitehead, K. et al. Managing diabetes with nanomedicine: challenges and opportunities. Nat Rev Drug Discov 14, 45–57 (2015). https://doi.org/10.1038/nrd4477 Project Gallery

A short exploration of the genetic predisposition behind human behaviours Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Can we blame our genes for excessive smoking and drinking? 07/05/26, 19:37 Last updated: Published: 13/01/24, 15:33 A short exploration of the genetic predisposition behind human behaviours The advancing research on how tobacco, alcohol addictions, and other detrimental behaviors are consequences of complex interplays between genetic and environmental factors has gradually developed and gained credibility. A collaborative effort involving over 100 international scientists, including researchers from the National Institutes of Health (NIH) and the National Institute on Drug Abuse (NIDA), embarked on a genome-wide association study (GWAS) to explore the heritable traits associated with tobacco and alcohol addiction. The study analyzed data from a sample size of 1.2 million biobanks, epidemiological research, and genetic testing companies, shedding light on the relationship between genetics and addiction behaviors. Researchers discovered that phenotypes related to smoking, such as when individuals began smoking habits, are genetically correlated with various diseases. In contrast, increased genetic risk for alcohol consumption is linked to reduced risk of many diseases. Previous studies pinpointed 10 genes involved in the risk of tobacco and alcohol addiction. In addition, this study further contributed to genetic links by identifying more than 400 locations in the genomes with over 500 variants associated with critical functions involving dopamine regulation, glutamate transmission and acetylcholine activation in the brain. Another study involving 3.4 million people with diverse ancestries suggested that approximately 3,823 genetic variants may impact addiction behaviors, with specific variants associated with the age at which individuals start smoking and the number of cigarettes or alcoholic drinks consumed. These studies could indicate a future where genetic screening for genes relevant to addiction behaviors is available, and this could be especially useful for those with relatives involved in certain addictions. Furthermore, it also provides perspective on whether certain genes can increase the likelihood of addiction to illegal drugs like cocaine, heroin or MDMA. However, increasing people’s awareness of whether they are at risk of developing addictions may be insufficient in deterring them from pursuing risky behaviors, which suggests that genetic screening for these genes would be beneficial as an optional screening assessment for individuals. While the influence of environmental and social factors on tobacco and alcohol addictions has long been acknowledged and explored, these studies underscore the significant role genetics plays in determining an individual’s susceptibility to nicotine and alcohol dependence. The prospect of predicting a person’s risk of addiction can lead to early interventions. Furthermore, it prevents countless health-related fatalities associated with smoking and alcoholic beverages. This primary prevention provides a different aspect to risk factors for smoking and alcohol addiction while also reducing the burden of these highly prevalent public health concerns. Written by Maya El Toukhy Related articles: Smoking cessation / Smoking and trigeminal neuralgia References: New Scientist (n.d.). Thousands of genetic variants may influence smoking and alcohol use. [online] New Scientist. Available at: https://www.newscientist.com/article/2350516thousandsofgenetic-variants-may-influence-smoking-and-alcohol-use/ [Accessed 23 Oct. 2023]. Today’s Clinical Lab. (n.d.). Do Your Genes Predispose You to Smoking and Drinking? [online] Available at: https://www.clinicallab.com/do-your-genes-predispose-you-tosmokinganddrinking-26963 [Accessed 23 Oct. 2023]. University of Minnesota. (2019). Hundreds of genes affecting tobacco and alcohol use discovered. [online] Available at: https://twin-cities.umn.edu/newsevents/hundredsgenesaffecting-tobacco-and-alcohol-use-discovered [Accessed 23 Oct. 2023]. Schlaepfer, I., Hoft, N. and Ehringer, M. (2008). The Genetic Components of Alcohol and Nicotine Co-Addiction: From Genes to Behavior. Current Drug Abuse Reviewse, 1(2), pp.124– 134. doi: https://doi.org/10.2174/1874473710801020124 . Project Gallery

Unlocking the mystery of spinal disorders and paving the way for targeted therapies Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Unveiling the cancer magnet: vertebral stem cells and spinal tumour metastasis Last updated: 29/05/25, 11:46 Published: 24/04/25, 08:00 Unlocking the mystery of spinal disorders and paving the way for targeted therapies Introduction Researchers at Weill Cornell Medicine have discovered that the vertebral bones in the spine contain a unique type of stem cell that secretes a protein-promoting tumour metastasis. This protein, called MFGE8, plays a significant role in attracting tumours to the spine, making it more susceptible to metastasis when compared to other bones in the body. A new line of research on spinal disorders This groundbreaking study , published in the journal Nature, sheds light on the mechanisms behind the preference for solid tumours to spread to the spine. The findings open up a new line of research on spinal disorders, potentially leading to a better understanding and treatment of bone diseases involving the spine. Identifying vertebral stem cells The researchers began their study by isolating skeletal stem cells, which are responsible for bone and cartilage formation, from various bones in lab mice. Through gene activity analysis, they identified a distinct set of markers for vertebral stem cells. Further experiments in mice and lab-dish cell culture systems confirmed the functional roles of these stem cells in forming spinal bone. Unravelling the mystery of spinal tropism Previous theories attributed the spine's susceptibility to metastasis to patterns of blood flow. However, the study's findings challenged this long-standing belief. Animal models reproduced the phenomenon of spinal tropism, but the researchers discovered that blood flow was not the sole explanation. Instead, they found evidence pointing towards vertebral stem cells as the possible culprits. The role of MFGE8 The researchers discovered that spinal tropism is largely a result of the protein MFGE8, which vertebral stem cells secrete in greater quantities than other bone stem cells. Removing vertebral stem cells eliminated the difference in metastasis rates between spine bones and other long bones. Implications for cancer patients These findings have significant implications for cancer patients, particularly those at risk of spinal metastasis. The researchers are now exploring methods to block the activity of MFGE8, aiming to reduce the risk of tumour spread to the spine. By understanding the distinctive properties of vertebral stem cells, researchers hope to develop targeted treatments for spinal disorders. A new frontier in orthopaedics According to study senior author Matthew Greenblatt, the identification of these unique stem cells opens up a new subdiscipline in orthopaedics called spinal orthopaedics. Many conditions in this clinical category may be attributed to the properties of vertebral stem cells. Further research in spinal orthopaedics is needed to understand how these distinct properties of vertebral stem cells contribute to spinal disorders. The discovery of MFGE8, a protein secreted in higher amounts by vertebral stem cells, has shed light on the mechanism behind the preferential spread of tumours to the spine. By investigating methods to block MFGE8, researchers hope to reduce the risk of spinal metastasis in cancer patients. Additionally, the study findings highlight the importance of understanding the role of vertebral stem cells in bone diseases that primarily affect the spine. This new line of research may provide insights into the development of novel treatments for spinal disorders. Conclusion In conclusion, the study by researchers at Weill Cornell Medicine has shown that vertebral bones, which make up the spine, contain a particular type of stem cell that secretes a protein known as MFGE8. This protein plays a significant role in promoting tumour metastases, explaining why solid tumours often spread to the spine. The findings have opened up new avenues of research in understanding spinal disorders and may lead to the development of strategies for reducing the risk of spinal metastasis in cancer patients. Overall, this study highlights the importance of vertebral stem cells in contributing to spinal disorders and emphasises the need for further investigation in this field. Written by Sara Maria Majernikova Related articles: Cancer metastasis / Brain metastasis / Stem cells REFERENCE Sun, J., Hu, L., Bok, S. et al. A vertebral skeletal stem cell lineage driving metastasis. Nature 621, 602–609 (2023). https://doi.org/10.1038/s41586-023-06519-1 Project Gallery

Recombinant adeno-associated viruses (rAAVs) Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link What you should know about rAAV gene therapy 14/07/25, 16:13 Last updated: Published: 01/10/23, 20:45 Recombinant adeno-associated viruses (rAAVs) Curing a disease with one injection: the dream, the hope, the goal of medicine. Gene therapy brings this vision to reality by harnessing viruses into therapeutic tools. Among them, adeno-associated viruses (AAVs) are the most used: genetically modified AAVs, named recombinant AAVs (rAAVs), are already used in six gene therapies approved for medical use. Over 200 clinical trials are ongoing. AAV, a virus reprogrammed to cure diseases Gene therapy inserts genetic instructions into a patient to correct a mutation responsible for a genetic disorder. Thanks to genetic engineering, researchers have co-opted AAVs (along with adenoviruses, herpes simplex viruses and lentiviruses) into delivering these instructions. Researchers have swapped the genes that allow AAVs to jump from person to person with genes to treat diseases. In other words, the virus has been genetically reprogrammed into a vector for gene transfer. The gene supplemented is referred to as transgene. Biology of AAVs AAVs were discovered in the 1960s as contaminants in cell cultures infected by adenoviruses, a coexistence to which they owe their name. AAVs consist of a protein shell (capsid) wrapped around the viral genome, a single strand of DNA long approximately 4,700 bases (4.7 kb). The genome is capped at both ends by palindromic repetitive sequences folded into T-shaped structures, the Inverted Tandem Repeats (ITRs). Sandwiched between the ITRs, four genes are found. They determine capsid components ( cap ) and capsid assembly ( aap ), genome replication ( rep ) and viral escape from infected cells ( maap ) ( Figure 1, top panel ). The replacement of these four genes with a transgene of therapeutic use and its expression by infected cells (transduction) lie at the heart of gene therapy mediated by rAAVs. Transgene transfer by rAAVs Researchers favour rAAVs as vectors because AAVs are safe (they are not linked to any disease and do not integrate into the genome), they can maintain the production of a therapeutic gene for over ten years and infect a wide range of tissues. In an rAAV, the ITRs are the only viral element preserved. The four viral genes are replaced by a therapeutic transgene, and regulatory sequences to maximise its expression. Therefore, an rAAV contains the coding sequence of the transgene, an upstream promoter to induce transcription and a downstream regulatory sequence (poly-A tail) to confer stability to the mRNA molecules produced ( Figure 1, bottom panel ). Steps of rAAV production Based on the disease, rAAVs can be administered into the blood, an organ, a muscle or the fluid bathing the central nervous system (cerebrospinal fluid). rAAVs dock on target cells via a specific interaction between the capsid and proteins on the cell surface that serve as viral receptors and co-receptors. The capsid mainly dictates which cell types will be infected (cell tropism). Upon binding, the cell engulfs the virus into membrane vesicles (endosomes) typically used to digest and recycle material. The rAAVs escape the endosomes, avoiding digestion, and enter the nucleus, where the capsid releases the single-strand DNA (ssDNA) genome, a process known as uncoating. The ITRs direct the synthesis of the second strand to reconstitute a double-strand DNA (dsDNA), the replication of the viral genome and the concatenation of individual genomes into larger, circular DNA molecules (episomes) that can persist in the host cell for years. Nuclear proteins transcribe the transgene into mRNAs; mRNAs are exported in the cytoplasm where they are translated into proteins. The rAAV has achieved successful transduction : the transgene can start exerting its therapeutic effects. A simplified overview of rAAV transduction is presented in Figure 2 . The triumphs of rAAV gene therapies rAAV gene therapies are improving lives and saving patients. Unsurprisingly, the most remarkable examples of this come from the drugs already approved. Roctavian is an rAAV gene therapy for haemophilia A, a life-threatening bleeding disorder in which the blood does not clot properly because the body cannot produce the coagulation Factor VIII. In a phase III clinical trial, Roctavian reduced bleeding rates by 85% and most treated patients (128 out of 134) no longer needed regular administration of Factor VIII, the standard therapy for the disease, for up to two years after treatment. Similar impressive results were noted for the rAAV Hemgenix, a gene therapy for haemophilia B (a bleeding disorder caused by the absence of the coagulation Factor IX). Hemgenix reduced bleeding rates by 65% and most treated patients (52 out of 54) no longer needed regular administration of Factor IX, for up to two years. The benefits of Zolgensma are even more awe-inspiring. Zolgensma is an rAAV gene therapy for spinal muscular atrophy (SMA), a genetic disorder in which neurons in the spinal cord die causing muscles to waste away irreversibly. The life expectancy of SMA patients can be as short as two years, therefore timing is critical. As a consequence, Zolgensma had to be tested in neonates: babies with the most severe form of SMA were dosed with the drug before six weeks of age and symptoms onset (SPRINT study). After 14 months, all 14 treated babies were alive and breathing without a ventilator, whilst only a quarter of untreated babies did. After 18 months, all 14 could sit without help, an impossible feat without Zolgensma. These and other resounding achievements are fuelling research on rAAVs gene therapies. Current limitations Scientists still have some significant hurdles to overcome : ● Packaging capacity: AAVs can fit in their capsids relatively short DNA sequences, which do not allow the replacement of many long genes associated with genetic disorders, ● Immunogenicity: 30-60% of individuals have antibodies against AAVs, which block rAAVs and prevent transduction, ● Tissue specificity: rAAVs often infect tissues which are not the intended target (e.g., inducing the expression for a transgene to treat a neurological disease in the liver rather than in neurons). Gene therapies, not only those delivered by rAAVs, face an additional challenge, this one only partially of a technological nature: their price tags. Their prices – rAAVs range from $850,000 (£690,000) to $3,500,000 (£2,850,000) – make them inaccessible for most patients. A cautionary tale is already out there: Glybera, the first rAAV gene therapy approved for medical use, albeit only in Europe (2012), was discontinued in 2017 because it was too expensive. Research is likely to reduce the exorbitant manufacturing costs , but the time may have come to reconsider our healthcare systems. Notes One non-viral vector exists , but its development lags behind the viral vector . Glybera for treating lipoprotein lipase deficiency, Luxturna for Leber congenital amaurosis, Zolgensma for spinal muscular atrophy, Roctavian for haemophilia A, Hemgenix for haemophilia B, and Elevidys for Duchenne muscular dystrophy. Written by Matteo Cortese, PhD Related articles: Germline gene therapy (GGT) / A potential treatment for HIV / Rabies / Antiretroviral therapy Project Gallery