A single-shot option for osteoarthritis now available from the Stempeutics-Alkem collaboration

A single-shot option for osteoarthritis now available from the Stempeutics-Alkem collaboration


An off-the-shelf option for knee osteoarthritis (OA) developed by biotechnology company Stempeutics will now be available to patients suffering from this debilitating disease. The allogeneic single-injection product, StemOne, will be marketed in India by drug-maker Alkem Laboratories.

There are different grades of knee OA and the single-injection option is recommended for those diagnosed as Grade 2 or 3, where there is still cartilage remaining in the joints, explains Manohar BN, Stempeutics Managing Director and Chief Executive. Advanced clinical trials on this regenerative product has shown that it prevents the condition from deteriorating, in that the cartilage is maintained and pain reduced, he said. Trials were done at 15 hospitals across the country in 146 patients over 65 years.

Alkem is pricing the product at ₹1.25 lakh (2ml vial), he told BusinessLine. But would that put the medicine beyond the reach of many? Manohar explains, the single-shot stem cell product prevents an individual’s condition from deteriorating, in the process averting a surgery (its cost and trauma). Besides, it is not a life-long therapy.

Break-through

The product is a break-through, because there are no “disease-modifying” medicines available, he said. Usually, patients are advised to follow non-pharma options including losing weight, then given pain medication, followed by inter-articular injections and steroids, he said. And if none of these work, they go in for a knee replacement surgery. About two lakh people in the country undergo surgeries, he said, estimated to be a ₹4,000 crore segment.

The stemcell product that can be used across genetically dissimilar patient profiles (allogeneic) is developed from the bone-marrow of healthy donors, he said, adding that three donors could support production of 90 lakh units. Armed with regulatory approvals to sell in India, Stempeutics is in discussion with the regulatory authority in the United States to undertake trials there, to eventually be able to sell there. About 19 million people in the US are estimated to suffer from the disease, he said. Stempeutics’ product pipeline includes a diabetes-oriented product and bio-cosmoceuticals.

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Stempeutics is a group company of Manipal Education and Medical Group. Drugmaker Cipla and Kemwell (a biologics contract development and manufacturing organisation) are also stakeholders in the company. Cipla markets Stempeutics’ first product, Stempeucel, used to treat Critical Limb Ischemia due to Buerger’s disease, where blood supply to the lower extremities of the body is cut off.





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Materials morph into cool green warriors

Materials morph into cool green warriors


The last time you or a family member sprained an ankle, your family doctor likely asked you to apply an ‘ice’ pack to help bring the inflammation down. After use, the pack would go back into the refrigerator to turn the melted water into ice again.

The water-ice combination is a classic example of a phase-changing material (PCM). When a material changes phase, it stores or releases energy and this freeze-thaw cycle is useful in applications that not only require maintaining a desired temperature but also a practical and cost-effective alternative to electricity and fossil fuels.

Air vs water

In a 2014 article in the CIGR journal  Agricultural Engineering International, authors Amandeep Sharma and Kulwinder Kaur explain why milk stored with ice packs is cooled faster than when carried in an air-cooled truck from farm to processing factory. They point out that air absorbs heat slowly.

For example, if a can of warm milk is placed in a room where the air temperature is at freezing point, it will take 12 hours to cool the milk to 10 degrees C. In contrast, water cools the milk more than 20 times faster than air. “When ice is present in the cooling tank, the heat from milk to the coolant is used up largely in melting of ice and, thus, enhances the efficiency of the cooling system.”

Prof Satya Seshadri at the Department of Applied Mechanics in IIT-Madras explains the concept: “When water turns to ice, it essentially gives up energy. When ice is placed along with, or inside of materials that require cooling, the ice regains the energy to turn into water but that energy is now extracted out of the materials that need to be cooled.” And, the cooling stays as long as all of the ice turns to water.

He has mentored Tan90 Thermal Solutions, a start-up that provides energy-efficient cold storage solutions to farmers.

Additionally, the use of nanoparticles has helped improve the energy storage-release property of water-based PCMs.

In a paper approved for publishing in the upcoming edition of the  Innovative Food Science & Technologies Journal, Ravi Prakash and Rekha Menon of ICAR-National Dairy Research Institute show that using titanium dioxide in water-based PCMs helps in quicker cooling of milk at the point of production. Their study used nanoparticles-enhanced PCMs (NePCM) inside the jackets of a cylindrical milk chilling module. They numerically simulated transient energy storage and its discharge during passive milk chilling, and then validated their conclusions with experiments.

The use of nanoparticles reduced “the charging time, supercooling degree, phase-transition time and the energy discharging time during milk chilling by 25.49 per cent, 47.05 per cent, 30.18 per cent and 42.90 per cent, respectively”.

The fresh raw milk was chilled from 37 degrees C to below 10 degrees C within one hour, and maintained below this safe limit using the NePCM inside the module.

They say there is scope for a rechargeable, portable and passive chilling-cum-storage unit for maintaining the cold-chain starting right from the milk production points in rural areas.

Localised solutions

Why could such research be important for a country like India? The authors point out in the paper that the pooled contribution by small-time farmers in total milk production is as high as 70–80 per cent. These farmers are located in rural areas, have small herds of five animals or less, and handle about 0.5 to tens of litres per head per milking. Given the low per capita volumes and distances between milking centres and processing units, bulk milk chillers are not useful for such producers. The fresh milk is usually handled in day temperatures going up to 40 degrees C for about 3-5 hours before they reach processing units. But fresh raw milk must be chilled soon after production to below the critical temperature limit of 10 degrees C to help preserve quality and safety for consumption. Without sufficient cooling mechanisms, the authors say, milk rejection rates are high, leading to revenue losses for small-time dairy farmers.

For temperatures far beyond the 0-degree point, such as –10 degrees C or +40 degrees C, different phase changing materials will be needed.

Pluss Advanced Technologies, now a subsidiary of Carborundum Universal of Murugappa Group, has been in the PCM arena for more than a decade. It offers cooling solutions for applications ranging from trucks carrying perishables to buildings that need cooling during the daytime, and hospitals for infant care.

In some countries in western Europe, summer night temperatures are 13-18 degrees Celsius. But daytime temperatures have been rising because of climate change, going up to 30 degrees C, which is seen as hot in those geographies. The company has executed cooling solutions for buildings in that region.

Says Samit Jain, the company’s managing director, “We have installed a 22-degree [Celsius] PCM in these buildings. In the daytime, when the room temperature gets to 23 or even 24 [degrees Celsius], nothing happens, but when it gets to 25 there is enough delta ‘t’ [or significant difference in temperature] between 22 and 26 and the PCM begins to melt.”

In other words, the PCM takes the heat from the room. So, the room temperature begins to stabilise around 25 degrees Celsius and will stay there till all the PCM is melted. Beyond this, air conditioners may be needed to maintain 25 degrees C.

“But by that time, the office is probably closed or, in the least, you’ve reduced your air conditioning requirement.” At night, with the aid of the cold air, the PCM again freezes. So, he says, “I’m getting what is called absolute free cooling — I have used the night-time cold to cool my building in the daytime.”

He says ice and water won’t work as PCM for these applications because they don’t change phases at 18-25 degrees C. Inorganic salts mixed with water in a certain proportion are preferred instead. While the identity of the material is a company secret, ‘calcium chloride’ is an example of such salts. Organic materials like paraffins or even bio-based oils could work but are avoided because they are flammable.

And if you were wondering where exactly the PCM is located in such applications, he says: “The PCM panels are laid between the ceiling and the false ceiling.”

Cleaner, cheaper

On energy savings, Jain says it is about 30 per cent for an area of 30,000 sq ft and 12 hours of operation.

Using PCM, the company has also helped implement space heating solutions at high altitudes for the Indian Army. The technology development was sponsored by the government’s Department of Science and Technology.

Similarly, for trucks that transport perishables, Pluss helps line containers with a PCM suited for the required temperature. Before the trip begins, the PCM is frozen or charged using electricity. The PCM melts during transit and lasts for the duration of the journey. Explains Jain, “Without PCM, the cooling system was active throughout the journey, using diesel to power the system. Diesel is twice as costly, and dirty, as electricity off the grid.”

Pluss offers a PCM-based solution for hospitals to prevent asphyxia in newborn children. “The standard care for a birth-asphyxiated baby is to maintain the baby at about 33 degrees C, instead of the 37 that humans need — helping lower their need for oxygen.

“Rural hospitals typically don’t have budgets to import cooling devices. And the problem of birth asphyxia is seen more in low-income groups.” The company developed the technology and equipment in collaboration with Christian Medical College, Vellore.

Two layers of PCM material go into an insulated cradle. One layer lowers the temperature to the 33-degree C range and can then be removed. The second layer helps sustain the temperature for the required 72 hours with minimum human intervention. A conduction mattress makes up the top layer on which the infant is placed.





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Intel’s onboard service to cut road accidents

Intel’s onboard service to cut road accidents


Around 1.5 lakh Indians are killed in road accidents each year — more than in any other country. To help deal with the problem, Intel has developed Intel® Onboard Fleet Services, an AI-powered safety solution for commercial vehicles. Designed for Indian conditions, it features in-cabin devices which offer advanced driver assistance system (ADAS) from Mobileye, collision avoidance systems (CAS), driver monitoring systems, fleet telematics, and fleet health and fuel efficiency features. The solution comes with a portal that includes actionable insights, analytics, and reports for fleet managers to help improve overall efficiency, enable preventive maintenance, and reduce operating costs.

“We have been working with our ecosystem collaborators, government, industry, and academia to implement cutting-edge technology solutions using AI, IoT, ADAS, to enable smarter and safer transportation for all,” says Kishore Ramisetty, Vice-President, Intel Foundry Services.

While the real-time alert calculations happen locally on the devices, post-analysis takes place in the cloud, which also analyses the driver’s behaviour using data collected over a period of time. The advanced telematics cover vehicle health and fuel analytics, along with a driver scoring and rating module. At the heart of the solution is driver coaching, which activates 15 different inputs to provide individualised coaching recommendations for commercial fleets.

The results show an almost 70 per cent improvement in safe driving practices, accident reduction by 40-60 per cent, overall efficiency loss reduction of up to 50 per cent, and a 75 per cent reduction in vehicle damage costs.

Ramratan Singhi, Founder and CEO of the Sure group, which owns a fleet of 125 vehicles  said that with Intel ® Onboard, accidents dropped from  20-25 major accidents to three minor accidents and zero major ones today.

 

Activated carbon from DRDO

The Defence Research and Development Organisation (DRDO) has come up with ‘activated carbon spheres’, an adsorbent with desirable qualities such as a porous structure, large surface area, high micropore volume, controllable pore size distribution, high mechanical strength, high purity, smooth surface, high wear-resistance, excellent durability, good fluidity, low ash content and low moisture content. ACS is commonly used in applications such as catalyst support, purification of blood, supercapacitors, protective suits against chemical warfare agents, and adsorptive removal of gaseous and liquid toxicants. Using polymeric precursors, specific surface area greater  than 800 sq m per gram along with total pore volume greater than 0.8 cubic cm per gram have been used for removal of toxicants. The application of activated carbon as adsorbents relies on the pore size and its distribution as micropores (less than 2mm) and mesopores (2-50 nm) that are mostly used for the gas phase and liquid phase. ACS has been successfully used for developing individual protective equipment (IPE) such as NBC (nuclear, biological, chemical) suit, socks, haversack and boot, says a note from DRDO.





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Using scorpion venom to fight superbugs

Using scorpion venom to fight superbugs


Can a scorpion’s sting destroy superbugs — the multidrug-resistant microorganisms (MDRO) that completely defy antibiotics?

WHO estimates that MDROs account for 700,000 deaths every year. It is the frequent overuse of antibiotics that has led to the evolution of superbugs. In its 2020 report, the Indian Council of Medical Research (ICMR) categorised pathogens causing serious infections into three groups based on their drug resistance capacity. The group 1 pathogens were resistant even to antibiotics used as a last resort.

Researchers at the Department of Biophysics, Panjab University, Chandigarh — in collaboration with the Department of Materials Science and Engineering, Yonsei University, South Korea — have been working with an antimicrobial peptide (AMP) found in scorpion venom that is seen effective against viruses, bacteria, parasites, and cancer cells.

AMPs are emerging as promising alternatives to antibiotics. (Peptides, like proteins, are chains of amino acids, only much shorter.)

Positively charged, AMPs act as the first line of defence against microorganisms in most living beings. While antibiotics act against pathogenic microorganisms with the help of the body’s innate immune system, AMPs kill microbes by targeting their plasma membrane, metabolic sites, and/or intracellular sites.

“To fight superbugs, AMPs either bind to the negatively charged plasma membrane (outer layer) of the microbes via electrostatic attraction or inhibit the intercellular processes (DNA, RNA and protein synthesis), eventually killing the microbes,” says Dr Ravi Pratap Barnwal, who heads the Punjab University research team.

Modern researchers have been looking at stabilised alpha-helical peptides (the alpha helix is a common pattern in the secondary structure of amino acids) as next-generation therapeutics. But such peptides were found to have limited functionality and stability due to their small size.

The Indo-Korean research has, on the other hand, focused on alpha-helical ligands (any molecule or atom that irreversibly binds to a receptor molecule) based on proteins that can make “steric clashes” with targets due to their large size. Notes Dr Barnwal, “Peptide-based alpha-helical ligands are good drug candidates for the regulation of biomolecular interactions due to their structural compactivity and design. Our current work involves developing a system where a pseudo-isolated alpha helix can exist in a monomeric (stable) state.

“This alpha helix can efficiently interact with deep and narrow targets from different pathogens (HIV, SARS-COV) and other diseases.”

The alpha helix ligands designed in this system do not require chemical modifications, have high thermal stability, and make favourable interactions just like isolated peptides.

“These peptides have the potential to replace conventional treatment approaches that involve antibiotics,” he adds.

But how did they zero in on scorpion venom? “The idea was inspired by the MP-1 peptide obtained from the venom of the Brazilian wasp. Venoms are a rich source of antimicrobial peptides.”

The AMPs in scorpion venom can enter microbial membranes by creating pores, and serve as antibiotic to help scorpions clean the biological conduits that carry venom to their stingers. Apart from anti-bacterial activity, scorpion AMPs have also been found to possess anti-viral, anti-cancer, anti-fungal, and anti-parasitic properties. The low toxicity of scorpion AMP also made it an ideal candidate for research, says Dr Gurpal Singh, another lead research member on the Indian side.

The research team for the antimicrobial peptide work included Dr Barnwal, Akshita Thakur, Akanksha Sharma, Dr Hema K Alajangi, and Dr Gurpal Singh (all from Panjab University), and Prof Yong-beom Lim and his team from Yonsei University. While for the alpha-helical peptides work, the team included Dr Barnwal, Mandeep Kaur, and Prof Lim and his team. 

Dr Barnwal has so far not been contacted by any pharmaceutical company for AMP/helical ligand in India. But Prof Lim is in talks with some pharma companies for product development in South Korea.

Published on

September 18, 2022



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Smart vaccine testing that safekeeps animals and humans

Smart vaccine testing that safekeeps animals and humans


In October 2021, after a three-decade wait, a vaccine for the leading killer disease malaria was finally approved. Traditional safety testing methods such as the monkey-based neurovirulence testing (MNVT) are usually time-consuming. However, after the SARS-CoV-2 virus upended the world, the pharma industry needed to deliver a family of vaccines on a deadline. Despite mandated screenings, some of them are being marked for breaching safety protocols and causing cardiotoxicity, neurovirulence, or even Guillain-Barré Syndrome.

Measuring neurovirulence

Neurovirulence is the capacity of a virus to cause diseases of the nervous system, and can have major repercussions on infected patients. All vaccines and drugs have to necessarily be screened for it. The gold standard in vaccine safety assessment today is the MNVT, which requires testing on primates to measure adverse impacts, especially neurovirulence. This methodology easily requires 8-9 months. The use of animal testing is riddled with ethical questions. Also, while primates offer a close approximation to humans, they are not the best substitution. There are also concerns over its predictive value. Hence, there has been a concerted search for more validated alternatives.

Revolutionary methodology

NeuroSAFE involves using stem cells in an in-vitro environment for vaccine safety testing — a revolutionary method that is non-animal, human-surrogate, and powered by artificial intelligence (AI). NeuroSAFE is a two-layered solution — first there’s the production and use of stem cells from biological discard such as umbilical cord tissue; then there’s a digital platform embedded with AI and machine learning (ML) tools that are trained to identify human non-clinical safety data like neurovirulence. The key differentiator is the use of image-based big data, which includes a wide range of authenticated neurovirulent responses as benchmark data sets.

When the test material is fed into the system, within minutes there is a response on the probability of neurovirulence, by comparing with the big data imprints. The traditional method, in contrast, would involve months and the sacrifice of 100-250 primates. The new methodology saves time (less than 10 minutes) and is cruelty-free. Moreover, the tests can be repeated multiple times for efficacy, and at a nominal cost, because testing labs are unnecessary for the methodology. There is also the important factor of stem cells mimicking human physiology more closely than MNVT results do, thus ensuring near-accurate results.

Additionally, it can be used for testing vaccines, adjuvants, small molecules, anti-venom, and cell- and gene-therapy. With this method, a company can go beyond mere screening and testing of vaccines to integrate it into any existing workflow as a key quality control test in vaccine production and other safety evaluation assays.

Cost savings

A grave condition such as neurovirulence may be caused by the final drug, an intermittent, or an adjuvant of any kind in vaccines. Hence, all candidates are mandated to be tested at the pre-clinical stage for potential risks. Moreover, most vaccines need to be assessed periodically. This leads to heavy dependency on testing laboratories and heavy costs. NeuroSAFE, on the other hand, is affordable, enables accurate testing that aligns with the 3R (reduction, refinement and replacement) principles in animal testing, and seamlessly integrates into the user’s workflow. With NeuroSAFE, companies can conduct multiple-level in-house screenings for discovery, development or testing.

Neurovirulence testing has a huge hidden cost — it not only puts animals at risk but also otherwise healthy people who ingest infected material. Breakthrough procedures such as NeuroSAFE can lead to new medical interventions while accelerating innovation and vaccine availability.

(The writer is CEO, NeuroSAFE)

Published on

September 18, 2022



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