Archive for category: E-News

E-News

14-year-old becomes youngest patient to receive living donor liver transplant at Cleveland Clinic Abu Dhabi

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live liver donor transplant

 

A 14-year-old boy has received a living liver donation from his elder brother at Cleveland Clinic Abu Dhabi, an integral part of Mubadala Health, becoming the youngest patient to undergo the operation in the hospital’s history.

Montasir Elfatih Mohyeldin Taha was diagnosed with biliary atresia in infancy, a condition where the bile ducts outside the liver fail to form during fetal development, not allowing the bile to reach the small intestine where it helps in the digestion of fat. At 10 months, he had to undergo the Kasai procedure, which is done to connect a loop of small bowel directly to the liver so that the bile can drain into it. Montasir’s doctors back home in Sudan knew that it was only a matter of time before he would have to undergo a liver transplant, an inevitable consequence for most children who have this procedure.

Portal hypertension

Earlier this year, Montasir’s symptoms and blood tests revealed that he had started developing liver failure and was suffering from portal hypertension, an increase in the pressure within the vein that carries blood from the digestive organs to the liver, resulting in varicose veins in his esophagus. Seeing the high risk of potential complications, his doctors in Sudan recommended that he undergo a liver transplant at Cleveland Clinic Abu Dhabi.

Dr. Luis Campos, the Director of Liver Transplant and Hepatobiliary at Cleveland Clinic Abu Dhabi, who was part of the interdisciplinary team that cared for Montasir, says this was one of the most complex living donor liver transplant surgeries that they have performed at the hospital.

“There were additional nuances that had to be taken into consideration because of his age, which made it even more challenging. Factors such as height and weight impact the surgery and after-care, and determine the dose of immunosuppressive medication during and after the transplant. There is also a risk of other infectious complications in pediatric liver transplant that do not apply to adult surgeries,” says Dr. Campos.

Multidisciplinary medical team

The multidisciplinary medical team at Cleveland Clinic Abu Dhabi studied the case and evaluated Montasir’s mother and brother for a match in February. After careful discussion with colleagues in the US-based Cleveland Clinic, doctors here decided that his sibling would be a more suitable match.

“My little brother needed me. I was very relieved when I was told that I can help be the cure to his illness. This was one of the easiest decisions that I have had to make,” says Khalifa Elfatih Mohyeldin Taha. “My father passed away six months back and as the eldest son in the family, it was my responsibility to save him.”

Kasai procedure

Dr. Shiva Kumar, the Chair of Gastroenterology and Hepatology in the Digestive Disease Institute at Cleveland Clinic Abu Dhabi, who was also part of the patient’s care team, says one of the biggest challenges during Montasir’s transplant was posed by the young patient’s Kasai procedure.

“While the Kasai procedure is commonly performed to prolong the need for a liver transplant in children, this is a major operation and makes the transplant more challenging to perform,” says Dr. Kumar.

“However, the surgeries of both brothers were successful and without complications. Montasir received a left lobe graft from his brother. This is a smaller portion of the liver than if we were transplanting a right lobe graft. This makes it a safer operation for the donor and helps them recover faster.”

Immunosuppressive regimen

The brothers are on their way to a full recovery. Khalifa is back to his normal life now while the Cleveland Clinic Abu Dhabi care team is monitoring Montasir’s immunosuppressive regimen, which he will be on for the rest of his life.

Khalifa says he could not contain his joy when he was told that the surgery was a success. “The best part of my transplant journey was to see that Montasir’s body had accepted the new organ. My family and I are very grateful to the care team at Cleveland Clinic Abu Dhabi for saving my brother’s life.”

He also hopes that more people consider organ donation. “The feeling of giving a chance to someone to live a normal life is incomparable. Seeing the result of your donation will fill you with contentment.”

Lung cells in patients with severe COVID become trapped in a state (indicated by the green color) that prevents the cells from repairing damage caused by the infection. The left image shows cells from a healthy lung; the right image shows lung cells from a patient who died from COVID-19

New Cell Atlas of COVID lungs reveals why SARS-CoV-2 is different and deadly

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Lung cells in patients with severe COVID become trapped in a state (indicated by the green color) that prevents the cells from repairing damage caused by the infection. The left image shows cells from a healthy lung; the right image shows lung cells from a patient who died from COVID-19.

Lung cells in patients with severe COVID become trapped in a state (indicated by the green color) that prevents the cells from repairing damage caused by the infection. The left image shows cells from a healthy lung; the right image shows lung cells from a patient who died from COVID-19. Images: Benjamin Izar / Columbia University Vagelos College of Physicians and Surgeons.

 

A new study published in Nature [1] draws the most detailed picture yet of SARS-CoV-2 infection in the lung, revealing mechanisms that result in lethal COVID-19, and may explain long-term complications and show how COVID-19 differs from other infectious diseases.

Led by researchers at Columbia University Vagelos College of Physicians and Surgeons and Herbert Irving Comprehensive Cancer Center, the study found that in patients who died of the infection, COVID-19 unleashed a detrimental trifecta of runaway inflammation, direct destruction and impaired regeneration of lung cells involved in gas exchange, and accelerated lung scarring.

Though the study looked at lungs from patients who had died of the disease, it provides solid leads as to why survivors of severe COVID may experience long-term respiratory complications due to lung scarring.

“It’s a devastating disease, but the picture we’re getting of the COVID-19 lung is the first step towards identifying potential targets and therapies that disrupt some of the disease’s vicious circuits. In particular, targeting cells responsible for pulmonary fibrosis early on could possibly prevent or ameliorate long-term complications in survivors of severe COVID-19,” says Benjamin Izar, MD, PhD, assistant professor of medicine, who led a group of more than 40 investigators to complete in several months a series of analyses that usually takes years.

This study and a companion paper [2] led by researchers at Harvard/MIT, to which the Columbia investigators also contributed, were published in the journal Nature on April 29.

Study creates atlas of cells in COVID lung

The new study is unique from other investigations in that it directly examines lung tissue (rather than sputum or bronchial washes) using single-cell molecular profiling that can identify each cell in a tissue sample and record each cell’s activity, resulting in an atlas of cells in COVID lung.

“A normal lung will have many of the same cells we find in COVID, but in different proportions and different activation states,” Izar says. “In order to understand how COVID-19 is different compared to both control lungs and other forms of infectious pneumonias, we needed to look at thousands of cells, one by one.”

Izar’s team examined the lungs of 19 individuals who died of COVID-19 and underwent rapid autopsy (within hours of death) – during which lung and other tissues were collected and immediately frozen – and the lungs of non-COVID-19 patients. In collaboration with investigators at Cornell University, the researchers also compared their findings to lungs of patients with other respiratory illnesses.

Drugs targeting IL-1ß may reduce inflammation

Compared to normal lungs, lungs from the COVID patients were filled with immune cells called macrophages, the study found.

Typically during an infection, these cells chew up pathogens but also regulate the intensity of inflammation, which also helps in the fight.

 

The lungs of patients with COVID-19 have more monocytes expressing IL-1beta than lungs from patients with other respiratory conditions.

 

“In COVID-19, we see expansion and uncontrolled activation of macrophages, including alveolar macrophages and monocyte-derived macrophages,” Izar says. “They are completely out of balance and allow inflammation to ramp up unchecked. This results in a vicious cycle where more immune cells come in causing even more inflammation, which ultimately damages the lung tissue.”
One inflammatory cytokine in particular, IL-1ß, is produced at a high rate by these macrophages.
“Unlike other cytokines such as IL-6, which appears to be universally prevalent in various pneumonias, IL-1ß production in macrophages is more pronounced in COVID-19 compared to other viral or bacterial lung infections,” Izar says. “That’s important because drugs exist that tamp down the effects of IL-1ß.”
Some of these drugs are already being tested in clinical trials of COVID patients.

Severe COVID also prevents lung repair

In a typical infection, a virus damages lung cells, the immune system clears the pathogen and the debris, and the lung regenerates.

But in COVID, the new study found that not only does SARS-CoV-2 virus destroy alveolar epithelial cells important for gas exchange, the ensuing inflammation also impairs the ability of the remaining cells to regenerate the damaged lung.

Though the lung still contains cells that can do the repairs, inflammation permanently traps these cells in an intermediate cell state and leaves them unable to complete the last steps of differentiation needed for replacement of mature lung epithelium.

“Among others, IL-1ß appears to be a culprit in inducing and maintaining this intermediate cell state,” says Izar, “thereby linking inflammation and impaired lung regeneration in COVID-19. This suggests that in addition to reducing inflammation, targeting IL-1ß may help take the brakes off cells required for lung repair.”

Preventing accelerated fibrosis

The researchers also found a large number of specific fibroblast cells, called pathological fibroblasts, that create rapid scarring in COVID-19 lungs. When the fibroblast cells fill the lung with scar tissue, a process called fibrosis, the lung has less space for cells involved in gas exchange and is permanently damaged.

Given the importance of pathological fibroblasts in the disease, Izar’s team closely analysed the cells to uncover potential drug targets. An algorithm called VIPER, developed previously by Andrea Califano, Dr, chair of systems biology at Columbia University Vagelos College of Physicians and Surgeons, identified several molecules in the cells that play an important role and could be targeted by existing drugs.

“This analysis predicted that inhibition of STAT signalling could alleviate some of the deleterious effects caused by pathological fibroblasts,” Izar says.

“Our hope is that by sharing this analysis and massive data resource, other researchers and drug companies can begin to test and expand on these ideas and find treatments to not only treat critically ill patients, but also reduce complications in people who survive severe COVID-19.”

References

[1] A molecular single-cell lung atlas of lethal COVID-19. Nature (2021).
https://doi.org/10.1038/s41586-021-03569-1

[2] COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets. Nature (2021).
https://doi.org/10.1038/s41586-021-03570-8

RESPIRE clinical trial

RESPIRE trial of therapeutic for all strains of COVID-19 gets underway in Germany

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RESPIRE clinical trial

 

Investigators hope ATR-002 drug will also be effective against ‘Long-Covid’

 

Tübingen, Germany-based Atriva Therapeutics, a biopharmaceutical company that is pioneering the development of host-targeting antiviral therapies, has enrolled its first patient in its Phase II RESPIRE [1] trial in COVID-19. Prof. Martin Witzenrath, M.D., Vice Director Department of Infectious Diseases and Respiratory Medicine, supervised the first administration of study medication (MEK inhibitor ATR-002 or placebo) at the Charité – Universitätsmedizin Berlin, Germany.

Dr Rainer Lichtenberger, CEO of Atriva Therapeutics, commented: “We are excited to assess the efficacy of ATR-002 in treating COVID-19 and are looking forward to the results of the clinical trial. We can now test our lead candidate against SARS-CoV-2 because our pharmacological target is a common cellular mechanism that RNA viruses use. ATR-002 leaves the virus itself untouched but blocks a cellular factor that the virus needs for its replication and has the potential to reduce the viral load in the infected host.

“Host-directed approaches maintain efficacy also against mutated viruses – a problem that we are commonly seeing in the influenza virus and, unfortunately, in SARS-CoV-2 as well. If we were to see the positive outcomes of the trial we hope for, ATR-002 could provide efficient help against COVID-19 regardless of the given genetic subtype of the underlying viral strain.”

Prof. Gernot Rohde, M.D., Head of Pneumology and Professor for Respiratory Medicine and Allergology at the Goethe University Hospital, Frankfurt am Main, Germany and Global Coordinating Investigator of the RESPIRE trial, said: “While we have been lucky that SARS-CoV-2 vaccines were developed at unprecedented speed, we still are in desperate need for effective therapies against COVID-19. The pandemic situation remains very critical and is far from being under control.

“Being able to contribute to the development of a COVID-19 therapy, I am very much looking forward to the effects that we may see with ATR-002. I am convinced that a medication that can prevent hospitalized patients with a moderate to severe stage of COVID-19 from deteriorating and requiring ICU admission and ventilator support would mean huge progress and could also play a role in impeding the severe long-term effects that are being described as “Long COVID” Syndrome (PASC).”

RESPIRE trial

RESPIRE is a randomized, double-blind, placebo-controlled, international, multi-center Phase II clinical trial in 220 adult patients with moderate to severe COVID-19, requiring hospitalization, but not requiring ICU admission or ventilator support at the time of screening or randomization. On top of standard of care, half of the patients will receive ATR-002 900 mg, administered as tablets once daily on day 1, followed by ATR-002 600 mg once daily on days 2 to 6. Patients in the control group will receive placebo in a matching scheme, on top of standard of care.

The primary objective of the study is to demonstrate the efficacy of ATR-002 versus placebo in addition to standard of care; secondary endpoints include the measurement of changes in clinical signs and symptoms as well as other relevant clinical parameters. Outcomes will be assessed based on the clinical severity status on day 15, using a 7-point ordinal scale as suggested by the WHO COVID-19 Therapeutic Trial Synopsis [2]. All patients will be followed-up for 90 days. The study will also evaluate the pharmacokinetics of ATR-002.

ATR-002’s mode of action

Atriva’s lead product ATR-002 is developed specifically to treat diseases such as influenza and COVID-19, caused by RNA viruses. ATR-002 is a clinical stage MEK inhibitor drug candidate targeting the intracellular Raf/MEK/ERK signaling pathway. This pathway is central for replication of many RNA viruses, such as the influenza virus, hantavirus or respiratory syncytial virus (RSV) and also SARS-CoV-2, the virus that causes COVID-19.

In influenza virus infected cells, the interaction of ATR-002 with MEK (MAPK/ERK kinase) prevents export of the viral genome protein complexes (ribonucleoprotein, RNP) from the nucleus to the cytoplasm, thus blocking the formation of functional new viral particles. This ultimately reduces the viral load in the body. In addition, ATR-002 has the potential to modulate the pro-inflammatory cytokine response of the body, avoiding overshooting cytokine response that can be caused by such viral infections. MEK inhibition can reduce the gene expression of some of the cytokines involved, like TNF-α, IL-1ß, IP-10, IL-8, MCP-1 and MIP-1a, and thus mitigate the overactive inflammatory response in the lungs of patients who are severely ill with influenza or COVID-19.

References

[1] RESPIRE – A Randomized, Double-Blind, Placebo-Controlled, Multi-Centre Clinical Trial to Evaluate the Safety and Efficacy of ATR-002 in Adult Hospitalized Patients with COVID-19.

[2] https://www.who.int/publications/i/item/covid-19-therapeutic-trial-synopsis.

covid-19 lung transplant

MedUni Vienna and Vienna General Hospital develop criteria for selecting COVID-19 patients for lung transplantation

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Early outcomes after lung transplantation for severe COVID-19In May 2020, a team led by thoracic surgeon Konrad Hoetzenecker of the Department of Surgery of MedUni Vienna and Vienna General Hospital performed a lung transplant on a 44-year-old patient who had been seriously ill with Covid-19, making her the first patient in Europe to receive a lung transplant for this indication. The Vienna lung transplantation programme now plays a leading role in an international consortium comprising experts from the USA, Europe and Asia. Based on the expertise from Vienna, approximately 40 transplants have now been carried out on Covid-19 patients throughout the world.

In a study published in The Lancet Respiratory Medicine, the consortium has now proposed the first general selection criteria for lung transplantation in Covid-19 patients.

“We have collated the first experiences in the world of performing lung transplants on Covid-19 patients. It is clear that such a complex intervention should only be considered for patients who, by virtue of their age and good general health, have a good chance of recovery with new lungs,” explaindc Konrad Hoetzenecker, Head of the lung transplantation programme at MedUni Vienna and Vienna General Hospital. The Vienna team performs around 100 lung transplants a year, making it one of the largest programmes in the world, alongside Toronto, Cleveland and Hanover.

Candidates for a lung transplant

The following factors were established as criteria for potential transplantation: exhaustion of all conservative treatment options, no recovery of the Covid-19-damaged lungs despite at least four weeks of ventilation/ECMO, evidence of advanced and irreversible lung damage in several consecutive CT scans, age below 65 and no relevant comorbidities. In addition to this, candidates for a lung transplant must be in good physical condition and have a good chance of complete physical rehabilitation following the transplant.

“These guidelines can be applied worldwide for making a sound selection of patients who are suitable for a lung transplant following a Covid-19 infection,” according to a statement released by MedUni Vienna.

The surgical team at MedUni Vienna and Vienna General Hospital has meanwhile carried out 12 lung transplantations on Covid-19 patients, demonstrating that even the most seriously ill patients, who would otherwise die, can survive with a lung transplant.

Patient No. 1

In March 2020, patient number one suffered total pulmonary failure as a result of Covid-19, so that artificial ventilation was no longer possible. She could only be kept alive by the circulation pump. At the time of the transplant, the PCR test showed that virus particles were still present but were no longer infectious. The MedUni Vienna/Vienna General Hospital thoracic surgeons and surgical team managed to replace the patient’s completely destroyed lungs with new donor lungs.

Reference:

Early outcomes after lung transplantation for severe COVID-19: a series of the first consecutive cases from four countries.
The Lancet Respiratory Medicine, 2021
https://doi.org/10.1016/S2213-2600(21)00077-1
https://www.sciencedirect.com/science/article/pii/S2213260021000771

Gold nanoparticles embedded in a porous hydrogel can be implanted under the skin and used as medical sensors© Nanobiotechnology Group, JGU Department of Chemistry

Implantable sensor made of gold nanoparticles could revolutionize medical diagnostics

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Gold nanoparticles embedded in a porous hydrogel can be implanted under the skin and used as medical sensors

Gold nanoparticles embedded in a porous hydrogel can be implanted under the skin and used as medical sensors. The sensor is like an invisible tattoo revealing concentration changes of substances in the blood by colour change.
— © Nanobiotechnology Group, JGU Department of Chemistry

Scientists at Johannes Gutenberg University Mainz (JGU) have developed a novel type of implantable sensor which can be operated in the body for several months to detect concentrations of substances or drugs in the body. Until now implantable sensors have not been suitable to remain in the body permanently but had to be replaced after a few days or weeks.

On the one hand, there is the problem of implant rejection. On the other hand, the sensor’s colour which indicates concentration changes has been unstable and faded over time.

The newly developed sensor is based on colour-stable gold nanoparticles that are modified with receptors for specific molecules. Embedded into an artificial polymeric tissue, the nanogold is implanted under the skin where it reports changes in drug concentrations by changing its colour.

Invisible tattoo

Professor Carsten Sönnichsen’s research group at JGU has been using gold nanoparticles as sensors to detect tiny amounts of proteins in microscopic flow cells for many years. Gold nanoparticles act as small antennas for light: They strongly absorb and scatter it and, therefore, appear colourful. They react to alterations in their surrounding by changing colour. Prof. Sönnichsen’s team has exploited this concept for implanted medical sensing.

To prevent the tiny particles from swimming away or being degraded by immune cells, they are embedded in a porous hydrogel with a tissue-like consistency. Once implanted under the skin, small blood vessels and cells grow into the pores. The sensor is integrated in the tissue and is not rejected as a foreign body.

“Our sensor is like an invisible tattoo, not much bigger than a penny and thinner than one millimetre,” said Prof Sönnichsen, head of the Nanobiotechnology Group at JGU. Since the gold nanoparticles are infrared, they are not visible to the eye. However, a special measurement device can detect their colour noninvasively through the skin.

In their study published in Nano Letters, the JGU researchers implanted their gold nanoparticle sensors under the skin of hairless rats. Colour changes in these sensors were monitored following the administration of various doses of an antibiotic. The drug molecules are transported to the sensor via the bloodstream. By binding to specific receptors on the surface of the gold nanoparticles, they induce colour change that is dependent on drug concentration. Thanks to the colour-stable gold nanoparticles and the tissue-integrating hydrogel, the sensor was found to remain mechanically and optically stable over several months.

Ideal platform for implantable sensors

“We are used to coloured objects bleaching over time. Gold nanoparticles, however, do not bleach but keep their colour permanently. As they can be easily coated with various different receptors, they are an ideal platform for implantable sensors,” explained Dr Katharina Kaefer, first author of the study.

The novel concept is generalizable and has the potential to extend the lifetime of implantable sensors. In future, gold nanoparticle-based implantable sensors could be used to observe concentrations of different biomarkers or drugs in the body simultaneously. Such sensors could find application in drug development, medical research, or personalized medicine, such as the management of chronic diseases.

Reference:
Implantable Sensors Based on Gold Nanoparticles for Continuous Long-Term Concentration Monitoring in the Body, Nano Letters, 30 March 2021. DOI: 10.1021/acs.nanolett.1c00887
https://pubs.acs.org/doi/10.1021/acs.nanolett.1c00887

INBRAIN Neuroelectronics team

Graphene nanotech neural implant company – INBRAIN Neuroelectronics – receives €14.35 million investment

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INBRAIN Neuroelectronics

INBRAIN Neuroelectronics, a spin-off Graphene Flagship partners the Catalan Institute of Nanoscience and Nanotechnology (ICN2) and ICREA, Spain, has received a €14.35 million Series A investment, one of the biggest rounds in the Spanish MedTech industry. The investment will allow INBRAIN to bring their novel neurotechnology to humans for the first time.

INBRAIN Neuroelectronics was established in 2019, at the intersection between MedTech, DeepTech and Digital Health, with a mission to decode brain signals to develop medical solutions for patients with epilepsy, Parkinson’s disease and other neurological disorders. The company designs small implantable brain intelligent systems – built around an innovative nanoscale graphene electrode – with the ability to interpret brain signals with unprecedented high fidelity, producing a therapeutic response adapted to the clinical condition of each patient.

 

Disruptive technology based on graphene

Existing brain interfaces are based on metals such as platinum and iridium, which impose significant restrictions in terms of miniaturisation and signal resolution, and therefore cause considerable side effects. For this reason, there is a 50% rejection rate in candidate patients. INBRAIN Neuroelectronics uses a disruptive technology based on graphene which will overcome the current limitations of metal-based neural interfaces.

INBRAIN Neuroelectronics team

INBRAIN is now a Graphene Flagship partner and is directed by Carolina Aguilar, who was the former Medtronic Deep Brain Stimulation European and Global Commercialization Director. The spin-off was founded, among others, by Graphene Flagship researchers in Spain and the UK, including Jose Garrido, researcher at Graphene Flagship partners ICN2 and ICREA; Kostas Kostarelos, researcher at Graphene Flagship partners ICN2 and the University of Manchester and Graphene Flagship Work Package Leader for Biomedical Technologies; and Anton Guimerà, researcher at Graphene Flagship partner IMB-CNM-CSIC. The technology development team consists of neurotechnology experts such as Bert Bakker (CTO) and Michel Decre (Technology Advisor & Board Member) from Philips, and other European successful neurotechnology start-ups.

 

According to a 2010 study commissioned by the European Brain Council, the cost of brain disorders in Europe alone is approximately €800 billion per year, with more than one-third of the population affected. Around 30% of patients with a neuronal disease are resistant to pharmacological treatment and do not have an effective therapy. The high incidence of brain-related diseases worldwide, and their huge social cost, call for greater investments in basic research in this field, with the aim of developing new and more efficient therapeutic and diagnostic tools.

In June last year, INBRAIN received a first-seed investment from a syndicate of investors led by Asabys Partners (through Sabadell-Asabys Health Innovation Investment) and Alta Life Sciences, including the Institut Català de Finances (ICF), Finaves (IESE Business School) and BStartUp. The most recent investment was co-led by Asabys Partners and Alta Life Sciences, and joined by Vsquared Ventures, a DeepTech-focused early-stage venture capitalist based in Munich; TruVenturo GmbH, Germany’s most successful tech and life science company builders; and CDTI, at the Spanish Ministry of Science and Innovation.

Cinzia Spinato, Graphene Flagship Business Developer for Biomedical Applications, said: “INBRAIN is leading the way in the field of graphene-based implantable brain devices, and I hope that this success will raise the interest of new stakeholders and corporates towards the opportunities graphene offers in the healthcare domain. I remember when INBRAIN was born, and it is impressive how they have grown so fast: transforming a laboratory technology into a product – an outstanding milestone. This investment will be fundamental to speed up the development of graphene-based medical devices, which will be tested on patients much earlier than everyone expected.”

Technological transformation

INBRAIN Neuroelectronics is bringing a complete technological transformation to the treatment of neurological diseases. Its brain implantable intelligent systems are based on graphene electrodes, which allow miniaturisation to nanoscale fabrication, with the potential to reach single-neuron resolution. The extraordinary properties of graphene – which is light, biocompatible, flexible and extremely conductive – are harnessed in much smaller devices that are safer to implant and can be programmed, upgraded and recharged wirelessly.

Driven by artificial intelligence, the implant can learn from the brain of each patient and trigger adaptive responses to deliver personalised neurological therapy. In addition, the use of big data management will permit remote monitoring of the device and data processing.

The technology has already been validated in in vitro and in vivo, and biocompatibility and toxicity tests have been successful. Studies on large animals have been completed and the investment will bring the technology to human patients, in collaboration with key neurosurgical and neurological groups in Europe.

“This substantial investment exemplifies the growing interest and ever-expanding opportunities to exploit graphene and layered materials in the biomedical domain. Due to its unique properties, graphene has the potential to transform this application area. The Graphene Flagship has chosen biomedical applications as a focus area for commercialisation, and continues to support efforts to foster new innovations – from research to the factory floor, now and into future.”
— Kari Hjelt, Graphene Flagship Head of Innovation

 

The Graphene Flagship, Funded by the European Commission, aims to secure a major role for Europe in the ongoing technological revolution, helping to bring graphene innovation out of the lab and into commercial applications.

Guillaume Blivet, co-founder and president of REGEnLIFE

REGEnLIFE’s trial of photobiomodulation technology for Alzheimer’s shows promising results

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Guillaume Blivet, co-founder and president of REGEnLIFE

Guillaume Blivet, co-founder and president of REGEnLIFE

REGEnLIFE, a company specialized in the research and development of innovative photo-medical technologies for the prevention and treatment of neurodegenerative diseases, has seen promising results of the pilot clinical trial evaluating its technology in Alzheimer’s disease (AD). The results were presented by Professor Jacques Touchon, scientific advisor on the trial, at the 15th International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD 2021), held online from March 9 to 14, 2021.

REGEnLIFE’s innovative non-invasive technology is based on photobiomodulation, targeting both the brain and gut via a helmet and abdominal device. This cutting-edge medical device, RGn530, stimulates cells in the brain and gut and regulates inflammation – to improve cognitive functions and behaviour. It targets inflammation of the gut-brain axis, which is believed to be linked to the development of AD and other neurodegenerative diseases.

“There are increasing scientific data to endorse the hypothesis that the gut-brain axis is involved in the development of AD and other neurodegenerative disorders. We also believe that some forms of electromagnetic emissions could prevent and treat this disease. Our initial clinical data, coupled with all our preclinical proof of concept studies, led us to pursue a pivotal clinical study in AD and to consider working on other neurological diseases,” said Guillaume Blivet, co-founder and president of REGEnLIFE. “To accelerate this new phase in our development and to shortly gain early market access, we are preparing a new funding round before the end of 2021.”

REGEnLIFE’s technology safe and well-tolerated
The trial enrolled adult volunteers aged 55 to 85, with mild to moderate Alzheimer’s disease. They were equipped with a helmet and a photobiomodulation abdominal belt; the patients benefited from a total of 40 sessions; these lasted for 25 minutes and were spread over a two-month period. The volunteers were evaluated in a series of tests during the trial and up to one month after treatment ended. This double-blind, randomized, monocenter, placebo-controlled clinical trial began in 2018; it ended prematurely in 2020 due to the COVID-19 pandemic. Out of the 64 planned patients, 53 were randomized into two groups (treated and placebo) and 43 patients benefited from the full duration of the treatment.

The primary efficacy endpoint was measured by the evolution of the total ADAS-Cog score, (Alzheimer’s Disease Assessment Scale), between inclusion and the end of the two-month period of treatment. The REGEnLIFE RGn530 device was shown to be safe; no major side effects were reported. Compliance with treatment sessions was very high for the vast majority of patients (92%). This level of compliance also confirms the good tolerance of the device. While the primary efficacy endpoint was not statistically met, there was a clear improvement trend in a set of cognitive functions. The results of this pilot study showed that REGEnLIFE’s technology is safe and well-tolerated by patients. These very encouraging safety and efficacy results will now be confirmed in a pivotal or phase III clinical trial.

“The therapeutic strategy for AD should involve several targets. Drug treatments targeting the two characteristic proteins of the Alzheimer’s process (beta-amyloid and tau proteins) must be supplemented by other therapies – targeting less specific but very important mechanisms in the pathophysiological AD cascade, such as inflammation and oxidative stress,” said Professor Jacques Touchon, neurologist and psychiatrist, scientific advisor on the clinical trial. “REGEnLIFE’s photobiomodulation technology acts at the early stages of this cascade, (mitochondria, inflammation, oxidative stress), and could be the non-drug complement to the next-generation therapeutic strategy. This technology also makes it possible to act on both the brain and the gut, a significant advantage when we know the important role of the gut-brain axis and microbiota in neurodegenerative pathologies.”

Photobiomodulation technology
Photobiomodulation is based on photonic emissions in the near-infrared, it has already shown analgesic, anti-inflammatory and healing properties. One of the most reproducible effects is the overall reduction in inflammation, especially in the brain < https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1016/j.trci.2017.12.003 >. REGEnLIFE’s technology could therefore be used on brain diseases and on pathologies linked to neuroinflammation. REGEnLIFE developed this device employing this scientific approach, using medical technology never before applied to neurology.

According to Alzheimer’s Disease International, 35 million patients worldwide have AD. The annual cost of the disease worldwide is estimated at €850bn. Currently, there are no treatments to cure Alzheimer’s.

In order to address public health issues related to a disease that affects elderly and vulnerable people, REGEnLIFE chose to develop a non-invasive technology with low constraints for patients. The cost of this device is expected to be reasonable for patients and national healthcare systems.

virtual events - good or bad?

Virtual events – does the industry like them?

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virtual events - good or bad?

Virtual events are likely to remain a firm fixture for some time, but do industry professionals like them? A recent survey found that while more than three quarters of survey respondents from the pharmaceutical and medical device sectors felt that virtual events would become much more popular in future – rivalling face-to-face events in number – they also highlighted aspects which have been unsatisfactory and need to be re-appraised by event organisers.

The survey by Owen Mumford Pharmaceutical Services which presents the impressions and predictions of industry professionals to date, serves as a wake-up call to event organisers.

Before COVID-19, the business events industry was economically massive, generating over $600 billion in GDP. The pandemic presented organisers with the challenge of rapidly reproducing events on online platforms. As we come to the end of a year of virtual conferences, webinars and podcasts, the question remains: ‘Are virtual events a suitable replacement for their face-to-face equivalents?’

To provide some early insight into this question specifically in the pharmaceutical and medical device industry, Owen Mumford Pharmaceutical Services commissioned research among top manufacturers. Respondents were asked to give their opinion, based on experience of virtual events throughout 2020, of what has worked and what has not.

Their responses make valuable reading for event organisers, as the benefits of virtual events – reduced travel time, reduced environmental impact and financial savings – will remain attractive even after the pandemic. Though the respondents have been underwhelmed by many virtual events so far (in terms of content, technical platforms, interactivity, price etc.), they remained positive about the potential for creating better experiences in the future. In fact, criticism of virtual events was most vehement where face-to-face methods had simply been ported online, with little thought about whether this would work satisfactorily for delegates.

“There are some areas of the in-person experience which are highly difficult to replace, especially the networking element which is so critical at conferences, and the ability to demonstrate a device and let delegates see how it works. But we see scope for innovative thinking from event organisers and this survey suggests that there is an appetite for this in our industry,” said Denis Marteau, General Manager at Owen Mumford Pharmaceutical Services.

SARS-CoV-2 virus

Study highlights risk of new SARS-CoV-2 mutations emerging during chronic infection

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SARS-CoV-2 virus

SARS-CoV-2 mutations similar to those in the B1.1.7 UK variant could arise in cases of chronic infection, where treatment over an extended period can provide the virus multiple opportunities to evolve, say scientists.

Given that both vaccines and therapeutics are aimed at the spike protein, which we saw mutate in our patient, our study raises the worrying possibility that the virus could mutate to outwit our vaccines

Writing in Nature, a team led by Cambridge researchers report how they were able to observe SARS-CoV-2 mutating in the case of an immune-compromised patient treated with convalescent plasma. In particular, they saw the emergence of a key mutation also seen in the new variant that led to the UK being forced once again into strict lockdown, though there is no suggestion that the variant originated from this patient.

Using a synthetic version of the virus Spike protein created in the lab, the team showed that specific changes to its genetic code – the mutation seen in the B1.1.7 variant – made the virus twice as infectious on cells as the more common strain.

SARS-CoV-2, the virus that causes COVID-19, is a betacoronavirus. Its RNA – its genetic code – is comprised of a series of nucleotides. As the virus replicates itself, this code can be mis-transcribed, leading to errors, known as mutations. Coronaviruses have a relatively modest mutation rate at around 23 nucleotide substitutions per year.

Of particular concern are mutations that might change the structure of the ‘spike protein’, which sits on the surface of the virus, giving it its characteristic crown-like shape. The virus uses this protein to attach to the ACE2 receptor on the surface of the host’s cells, allowing it entry into the cells where it hijacks their machinery to allow it to replicate and spread throughout the body. Most of the current vaccines in use or being trialled target the spike protein and there is concern that mutations may affect the efficacy of these vaccines.

UK researchers within the Cambridge-led COVID-19 Genomics UK (COG-UK) Consortium have identified a particular variant of the virus that includes important changes that appear to make it more infectious: the ΔH69/ΔV70 amino acid deletion in part of the spike protein is one of the key changes in this variant.

Although the ΔH69/ΔV70 deletion has been detected multiple times, until now, scientists had not seen them emerge within an individual. However, in a study published today in Nature, Cambridge researchers document how these mutations appeared in a COVID-19 patient admitted to Addenbrooke’s Hospital, part of Cambridge University Hospitals NHS Foundation Trust.

Reference:

https://doi.org/10.1038/s41586-021-03291-y

cell

Hidden genes could be key in development of new antibiotics

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cell

A study from the Centre for Phage Technology, part of Texas A&M’s College of Agriculture and Life Sciences and Texas A&M AgriLife Research, shows how the “hidden” genes in bacteriophages – types of viruses that infect and destroy bacteria – may be key to the development of a new class of antibiotics for human health.

The study has been published in Nature Communications and Current Science Daily, as well as featured in a recent Nature Research Microbiology Community blog post.

Antibiotic-resistant bacteria pose an increasing threat to human health, creating an urgent need for the development of novel antibiotics.

“There has been an increased interest in bacteriophages and their potential as antibacterial agents to fight pathogenic bacteria,” said Centre for Phage Technology director Ryland Young, Ph.D., who supervised the study research. “This is in large part due to the ability of the ‘lysis genes’ of the phage to cause a cellular breakdown in the bacterial host.”

The need for new and more effective antibiotics has increased interest in bacteriophages as possible agents to fight pathogenic bacteria.

Most phages can cause their host cell to rupture, a process called lysis. They also release new “progeny” phage virions that are genetically and structurally identical to the parent virus.

“Small phages, such as the ones this study focuses on, make a single protein which causes host lysis,” Young said. “Basically, the virus produces a ‘protein antibiotic’ that causes lysis in the same way antibiotics like penicillin do – by disrupting the multistage process of cell wall biosynthesis. When the infected cell tries to divide, it blows up because it can’t create the new cell wall between the daughter cells.”

He said these small lysis proteins can be the model for a completely new class of antibiotics.

The study focuses on characterizing the lysis genes of leviviruses, bacteriophages containing small single-stranded RNA genomes with only three to four genes. Tens of thousands of leviviruses have been discovered. Among the known levivirus genes is Sgl, which stands for ‘single gene lysis.’ Sgl encodes a protein that induces the cellular breakdown of bacteria.

“We wanted to discover these ‘hidden’ lysis genes in single-stranded RNA phages, as well as understand how their structure and evolution could benefit development of new, more effective antibiotics,” said Karthik Chamakura, Ph.D., a postdoctoral research associate at the centre and the study’s first author. “We also wanted to investigate how certain molecular targets within bacteria could be identified and exploited for antibiotic development.”

Reference:

https://doi.org/10.1038/s41467-020-19860-0

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