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💉 A human brain cell atlas; BioNTech’s latest ADC investment; Daiichi Sankyo’s mRNA combo shot
#449 | Engineering bacteria to infiltrate tumours; Inhibiting enzymes to regenerate nerves; Drinking coffee to keep the kilos off
Hello there. Welcome back to The Kable for the final time this week. We hate to start an edition on a disheartening note, but today is just one of those days. Turkana County in northwestern Kenya has long been thought to be hidden from the clutches of malaria. It was too dry for mosquitoes, apparently. However, a study from Duke Global Health Institute and Kenya’s Moi University shows that the disease is already endemic in the region. Worse still, the Plasmodium vivax parasite – uniquely difficult but historically almost non-existent in sub-Saharan Africa – has made significant inroads here. This may not only reverse East Africa's progress in controlling malaria, but also urge public health officials to rethink what they know about malarial hot spots.
Over in Nigeria, over 600 people – mostly children – have died of diphtheria since December last year. Compared to the last outbreak in 2011 in which 98 cases were reported, this one is far worse, with 14,000 suspected cases.
For 6 years now, Kenya and Cuba had a deal under which the latter’s doctors were employed in Kenya’s county hospitals while Kenyan doctors received specialised training in Cuba. But this agreement was far from popular amongst Kenyan doctors, and with good reason – Cuban doctors were paid more than double the average salary of their Kenyan counterparts. Worse, Kenya itself had thousands of unemployed doctors and specialists. Kenya’s Health Minister has announced that the country will not renew the deal. Yay!
Meanwhile, in Ghana, the exodus of nurses has taken a major toll on the country’s healthcare systems. The Ghana Registered Nurses Association proposes that countries like Canada, whose health systems benefit immensely from international recruitment, should provide payment to support the training of more nurses in Ghana.
Back in Kenya, Roche Diagnostics and the Aga Khan University Hospital in Nairobi have inked a contract to enhance healthcare access in East Africa. The deal involves installing a fully automated diagnostics instrument to accelerate disease testing capacity for communicable and non-communicable diseases. The larger goal is to not only localise testing but also attract medical tourism.
Egypt, meanwhile, wants to cooperate with Pakistan in the fields of health and pharma. Egypt proposed exchanges of knowledge and human resources for mutual benefit. Egypt also offered the South Asian nation technical support and training to eliminate hepatitis C.
In the UAE, healthcare firm M42 has developed a clinical LLM, Med42, to provide high-quality answers to medical questions. Free to use, the company hopes the tech will act as an AI assistant to health professionals.
Moving eastwards, in Bangladesh, dengue continues to do what dengue does. In the 24 hours leading up to yesterday morning, 13 patients died, and 2,327 were hospitalised.
Speaking of dengue, Vietnam will join the trial of a Japanese single-dose dengue vaccine.
Speaking of Japan, the country’s Daiichi Sankyo is developing a combination mRNA shot against both Covid-19 and the seasonal flu. This project will have financial support from the Strategic Centre for Biomedical Advanced Vaccine R&D for Preparedness and Response, which is the government’s vaccine development command centre.
Speaking of Covid-19 vaccines, we come to BioNTech. Six months after its entry into the field of antibody-drug conjugates (ADCs), BioNTech has acquired the rights to develop, manufacture, and commercialise an ADC which targets HER3 protein-expressing tumours. The German company is shelling out $70 million upfront for this deal with China-based MediLink Therapeutics. This puts BioNTech in potential competition with Daiichi Sankyo.
In more Big Pharma news, Eli Lilly’s experimental drug Mirikizumab for moderately to severely active Crohn’s disease achieved the co-primary and all major secondary endpoints in a phase 3 study, which will be the basis of the company’s marketing applications.
Emerging from stealth mode, Israeli biotech startup Mana.bio has launched its AI-based solution to design lipid nanoparticles and create programmable drug treatments.
And finally, taking a cue from France, the European Food Safety Agency is recommending preventative bird flu shots for susceptible poultry in high-risk areas.
The Week That Was
What a packed edition Monday had. The Pharmacopoeial Discussion Group, or PDG, announced that the Indian Pharmacopoeia Commission, or IPC, is now a member of the group established by the European, Japanese, and US Pharmacopoeiae. With India producing many pharmaceutical drugs supplied worldwide, the IPC’s inclusion in the PDG marks a milestone in expanding the recognition of harmonised pharmacopoeial standards.
Analysts estimated that the market for GLP-1 agonists could be worth as much as $100 billion within a decade. This soaring demand for weight loss drugs is also sending the demand for firms that fill syringes skyrocketing. Consequently, contract drug manufacturers are investing billions of dollars to expand or build factories to fill injection pens.
Bristol Myers Squibb announced that it is acquiring cancer drug developer Mirati Therapeutics for over $4.8 billion, beating Sanofi to the chase. BMS' main interest is Mirati’s lung cancer drug Krazati, which targets tumours driven by KRAS mutations.
Monday may have been busy, but Tuesday not so much. Though there was some big news - in a massive boost for self-sufficiency in Africa, the Bill & Melinda Gates Foundation announced that it was donating $40 million to enhance access to mRNA vaccines in the continent, including a $20 million grant to Belgian biotech firm, Quantoom Biosciences, to further its mRNA manufacturing platform, Ntensify. Additionally, the Institut Pasteur de Dakar in Senegal and Biovac in South Africa will receive $5 million each to purchase this technology, with another $10 million earmarked for other interested vaccine manufacturers. Ntensify could potentially halve vaccine development costs in comparison to conventional mRNA technologies.
Plus, the World Stroke Organization-Lancet Neurology Commission predicted a 50% increase in global stroke deaths by 2050, reaching nearly 10 million, with the majority occurring in low- and middle-income countries.
Wednesday was a day for WHO reports. The WHO released its first roadmap to tackle postpartum haemorrhage, which though preventable and treatable, claims 70,000 lives annually – 85% of which are in sub-Saharan Africa and South Asia.
The second WHO report, Overview of Methods to Assess Population Exposure to Ambient Air Pollution, helps countries protect their people from bad air. 7 million people die prematurely from air pollution exposure every year. The report provides an overview of the strengths and weaknesses of different air pollution measurement and modelling methods. Overall, this report is useful for policymakers and government officials to assess their country’s air quality baseline level and develop plants to monitor air quality and manage their data.
Yesterday was all about second chances. Indian pharma manufacturer Marion Biotech’s cough syrups were linked to the deaths of 65 children in Uzbekistan last year. The drug controller of the state of Uttar Pradesh had cancelled the company’s license in March, but subsequent to an appeal, Marion is getting a second chance - the state health department has now allowed Marion to resume most production at its factory.
Smallpox is the only disease humankind has eradicated. What might be the second disease to join that category? Wild polio. To say goodbye to wild polio once and for all, the European Commission, the Bill & Melinda Gates Foundation, and the European Investment Bank shook on a brand new financing package worth about €1.1 billion.
And finally, only the second effective malaria vaccine we have – Oxford’s R21/Matrix-M shot – was recently recommended by the WHO. Yesterday, UNICEF announced an agreement to secure supply of the vaccine.
A deep dive into your brain. The brain is a highly complex organ, with nearly 100 billion neurons and more non-neuronal cells. Mapping all of those out seems like an unattainable goal, doesn’t it? Not to these guys. Adding to the Human Cell Atlas, scientists from the University of California in San Diego, the Salk Institute, the University of Washington Allen Institute for Brain Science, and the Karolinska Institute in Sweden have published an atlas of human brain cells.
Systematically surveying the entire human brain from front to back and inside out, this most detailed human brain cell catalogue yet shows that the brain has over 3,000 unique cell types – that’s about 10 times more than we earlier knew. It unveils new insight into how brain cell genes are used, what drives diseases, and how scientists can develop targeted therapies. Largely funded by the National Institutes of Health (NIH), this $250 million cellular parts list is the result of a five-year effort called the BRAIN Initiative Cell Census Network, or BICCN.
Three studies published today in Science present the brain map, while another 19 articles have also been produced under BICCN. These additional studies not only add more detail to the project but also use the data to address questions linked to brain changes during development across individuals and species. Overall, this ambitious project has revealed that neurons adopt very different identities in different brain parts, showcasing a large degree of diversity. Further, evolutionarily older brain parts like the brainstem show greater complexity. The catalogue can also help scientists assess what aspects of psychiatric diseases are suitable to be examined in animal models. Most interestingly, the team has already identified 107 different cell types and linked their molecular biology to schizophrenia, bipolar disorder, Alzheimer’s disease, and depression. Unearthing these links helped them to create algorithms that predict the effects of DNA sequence variations on gene regulation and disease – not just in humans but across species. By mapping similarities and dissimilarities across species, this atlas points to what makes the human brain distinctive.
Probiotics for cancer. Researchers from Columbia University have pioneered a probiotic-guided chimeric antigen receptor (CAR)-T platform, ProCAR, which ingeniously uses engineered bacteria to infiltrate solid tumours, produce synthetic antigen targets, and guide CAR-T cells to detect and annihilate tumour cells on-site. Developed using a non-pathogenic strain of E. coli, the engineered probiotic bacteria infiltrate tumour environments and release synthetic CAR targets cyclically, “tagging” the tumour so that the engineered CAR-T cells can home in to decimate the tumour cells.
This innovative two-stage platform represents a potential breakthrough for treating solid tumours – historically a challenge due to their antigen heterogeneity and resistance to T-cell infiltration. The method has demonstrated efficacy in reducing tumour volume in preclinical tests, using humanised and immunocompetent mouse models of various cancers. While further development is imperative for clinical application, this strategy paves the way toward extending CAR-T cell therapy to solid tumours by leveraging the tumour-targeting ability of engineered probiotic bacteria to guide immunotherapy.
Enzyme enables nerve regeneration. In a mouse model study by researchers at Stanford University School of Medicine and Sanford Burnham Prebys, an enzyme linked with ageing, 15-hydroxyprostaglandin dehydrogenase (15-PGDH), was found to be instrumental in nerve regeneration and recovery after injury. The findings revealed that inhibition of 15-PGDH with a small molecule elevated prostaglandin E2 (PGE2) levels in muscle tissues, facilitating the restoration of nerve connectivity and strength. This discovery is pivotal as there are no approved treatments for peripheral nerve function loss for various reasons including trauma and ageing. Moreover, the occurrence of 15-PGDH in diverse human neuromuscular diseases, as observed in human tissue studies, suggests the potential widespread applicability of inhibiting this enzyme as a therapeutic strategy, sparking hope for developing treatments that enhance nerve regeneration and muscle strength recovery by leveraging the body's own repair mechanisms.
(Science Translational Medicine)
Grab a cuppa Joe! A new study has found a modest link between coffee consumption and a slight mitigation in expected weight gain. The research used data from three substantial US studies, examining the Nurses’ Health Studies and a Health Professional Follow-up study, collectively encompassing hundreds of thousands of participants. An interesting correlation emerged, indicating that participants who increased their coffee intake by an additional cup daily experienced slightly less weight gain, about 0.12 kg, than anticipated over four years. Notably, introducing sugar into the mix did result in slightly greater weight gain than expected, whereas adding milk or a non-dairy alternative did not show a significant impact on this subtle weight fluctuation.
Despite the extensive sample size and duration providing a robust foundation for the study, it is crucial to underline that the findings illustrate an association rather than causation between coffee consumption and minimised weight gain, meaning the study does not definitively assert that coffee intake is the direct cause of the observed weight alterations. Moreover, the weight changes highlighted are indeed modest and might not substantiate a meaningful or practical approach to weight management for most individuals. Also worth noting is that the study does not account for the potential variability in caffeine content per cup of coffee, merely presuming a standardised amount. Thus, while the study provides a compelling perspective, its real-world applicability and significance in the realm of weight management might be viewed with a measured perspective. That, however, should be no reason for you not to reach for that cuppa cappuccino right now. Go ahead; you know you want it. You can tell everybody it was a Kable recommendation.
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