Category Archives: Cell Medicine

The news that Formula One legend Michael Schumacher was moved to a hospital in Paris last week for pioneering stem cell therapy has provoked a fever of hope and speculation among fans that his condition could be improved.

After suffering devastating head injuries in a ski accident almost six years ago, Schumacher was placed in a coma for six months and has been receiving treatment at his home in Switzerland. He has not been seen in public since the accident.

His privacy is closely guarded and, while it is understood he cannot walk or stand, and, according to former Ferrari manager, Jean Todt, he may still have trouble communicating, nothing has been confirmed officially.

No wonder then that fans have been so excited to hear Schumacher is now under the care of world-renowned cardiac surgeon Philippe Menasch, described as a "pioneer in cell surgery" at the Georges-Pompidou hospital in Paris.

READ MORE:* Schumacher 'conscious' after treatment*Corinna Schumacher provides rare update*Schumacher 'struggles' to communicate*Mick Schumacher trying to emulate his dad

Stem cells are cells that can differentiate or change into other types of cell, opening the possibility of replacing damaged cells with healthy ones. Scientists have been looking into their use since the Sixties, most successfully so far in cases of cancers of the blood or bone marrow. More than 26,000 patients are treated with blood stem cells in Europe each year.

And since the Eighties, skin stem cells have been used to grow skin grafts for patients with life-threatening burns; most recently, a new stem cell-based treatment to repair damage to the cornea (the surface of the eye) after an injury like a chemical burn, has received conditional approval in Europe.

But their flexibility offers hope for lots of illnesses and conditions including heart disease, MS and macular degeneration and clinical trials are progressing in all these areas. Chronic spinal cord injury is being researched with some promise, thanks to the Christopher & Dana Reeve Foundation, set up after actor Christopher Reeve was paralysed in a riding accident.

Crucially, for cases such as Schumacher, stem cells are also being explored for neurodegenerative diseases like Parkinson's and Alzheimer's and traumatic brain injuries like the one he suffered in a skiing accident in December 2013.

Head injuries are difficult to treat as brain damage cannot be undone and each case is different. Asked for comment by The Daily Telegraph, the hospital responded that they could neither confirm nor deny the presence of Schumacher.

However, if he is under the care of Menasch, it is likely he will have had stem cells delivered by an IV to the area of the body where it is felt they could work best - whether that is his head or heart.

CHRISTOPHE ENA/AP

Paris' Georges-Pompidou Hospital, where Michael Schumacher is reportedly a patient.

In a recent interview online, Menasch explained that stem cell treatment for cardiac conditions - his particular area of expertise - is in its infancy. "Nobody really knows how stem cells are working," he said. "They do not permanently transplant into the myocardium [the muscular tissue of the heart] - after a couple of days or weeks, they just disappear.

"But you still may have a functional benefit as during their transient stay in the heart," he explains in the Future Tech podcast, "as the cells release molecules into the tissue. The hypothesis is that the repair comes from the heart itself, stimulated by these molecules."

Should the stem cells have been intended for Schumacher's brain injury, research suggests that the treatment has potential. A University of Plymouth study published in the journal Cell Reports in June found that neural stem cells could be used to "wake up" and produce new neurons (nerve cells) and surrounding glial cells in the brain.

The research is in its infancy, says lead author Dr Claudia Barros, from the Institute of Translational and Stratified Medicine at the University of Plymouth, who acknowledges there is still a long way to go until such findings can be translated into human treatments.

"We are working to expand our findings, to bring us closer to the day when human neural stem cells can be controlled and efficiently used to facilitate brain damage repair, or even prevent brain cancer growth that is fuelled by stem-like cells," she says.

A Chinese study published last month in the journal Frontiers in Cellular Neuroscience examined the current state of progress into the effects of stem cell therapy on traumatic brain injury. But the researchers from Zhejiang University, Hangzhou warned much more work was needed: "Although a large number of basic studies have confirmed that stem cells have good effect in the craniocerebral injury," they said, "the safety of stem cells, the route of injection, the time of injection and the specific mechanism are all factors that affect the clinical application of stem cells, and are the important research point in the future study."

PREMA TEAM

Mick Schumacher doesn't mind the comparisons with his seven-time F1 champion father Michael.

In the UK, some applications of stem cell medicine are already available privately, although tightly controlled by the Human Tissue Authority and not in the brain.

Simon Checkley, CEO at the Regenerative Clinic in Brighton, explains: "It is possible to get stem cells from sources outside your body, like the umbilical cord or Wharton's jelly [the vitreous humour in the eyeball], but in the UK we can only take stem cells from our own bodies.

"It is possible to get them donated, but it is safer to use your own."

In some countries, stem cells can then be manipulated in a laboratory but that is illegal in the UK, says Checkley. "There is a concern with cultured stem cells which have been bred in a Petri dish that they may keep proliferating after you transplant them into a body. That, having triggered their growth, you can't stop it and no one knows what might happen."

At the Regenerative Clinic, stem cells are taken from adipose fat, where they are plentiful, and then injected back into the area to be treated - mostly arthritic joints.

"We are seeing fantastic results," Checkley says, "with reduced pain and improved mobility for 80 per cent of patients." He is considering a clinical trial which could see the treatment pass through the National Institute for Health and Care Excellence (NICE) and become available on the NHS.

The therapy is still only four years old, he emphasises. "We have treated 1000 patients so far and around the world, it's about 40,000. We need longer-term studies."

LUCA BRUNO/AP

Michael Schumacher has not been seen in public since suffering a serious brain injury in a skiing accident nearly six years ago.

This type of stem cell treatment is also offered in the UK for post-menopause vaginal atrophy and stress incontinence, Checkley says, plus the genital skin condition lichen sclerosis. In all these cases, he says, the mechanism is the same: the stem cells are not replicating dead or dying cells but acting as signalling devices, alerting the body that this is an area where healing is needed.

For stem cells to work in more complex conditions, they would need to be manipulated, Checkley says. In cases of brain injury or disease, that would mean altering stem cells so that they could be targeted more precisely. But he believes the role would be similar: "The idea is they would go to the area of greatest damage and signal the body to regrow tissue there."

Cost would be a huge factor, he points out. A treatment for arthritis costs about 6000 (NZ$11,700) at the Regenerative Clinic but an IV-led treatment for brain injury with manipulated stem cells could cost up to 50,000 (NZ$98,000). But then what price recovery from a traumatic brain injury? Full recovery thanks to stem cells would be a prize beyond value.

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Reported stem cell treatment could give hope to Michael Schumacher - Stuff.co.nz

Several recent studies in high-profile journals reported to have genetically engineered neurons to become responsive to magnetic fields. In doing so, the authors could remotely control the activity of particular neurons in the brain, and even animal behaviorpromising huge advances in neuroscientific research and speculation for applications even in medicine. We envision a new age of magnetogenetics is coming, one 2015 study read.

But now, two independent teams of scientists bring those results into question. In studies recently posted as preprints to bioRxiv,the researchers couldnt replicate those earlier findings.

Both studies . . . appear quite meticulously executed from a biological standpointmultiple tests were performed across multiple biological testbeds, writes Polina Anikeeva, a materials and cognitive scientist at MIT, to The Scientist in an email. I applaud the authors for investing their valuable time and resources into trying to reproduce the results of their colleagues.

Being able to use small-scale magnetic fields to control cells or entire organisms would have enormous potential for research and medical therapies. It would be a less invasive method than optogenetics, which requires the insertion of optical fibers to transmit light pulses to specific groups of neurons, and would provide a more rapid means of inducing neural activity than chemogenetics, which sparks biochemical reactions that can take several seconds to stimulate neurons.

In a 2016 study in Nature, geneticist Jeffrey Friedman from Rockefeller University and colleagues reported to have stimulated neural activity in glucose-sensing neurons in the mouse hypothalamus. Those neurons fired when the animals were exposed to a magnetic field, causing blood glucose concentrations to rise and insulin levels to fall. Ultimately, the mice ate more.

What I find most impressive about these reports . . . is just the level of care and effort that has gone into this.

Markus Meister, Caltech

The researchers did so by genetically engineering a construct to be expressed specifically in those neurons. The introduced sequences coded for the iron-based blood cell protein ferritin coupled to the TRPV1 membrane channel, a temperature-sensitive protein that allows positively charged ions such as calcium to enter cells. Stimulation of ferritins iron through a magnetic field was thought to prompt TRPV1 to open, although the precise mechanism is unclear.

In a different 2016 study in Nature Neuroscience,neuroscientist Ali Gler of the University of Virginia and colleagues used a similar construct they named Magnetothis time coupling ferritin to the TRPV4 membrane protein, sensitive to mechanical forces as well as temperature changes. Expressing this in dopamine-receptor neurons in the mouse striatum caused the rodents to preferentially spend time in a magnetized area of their cage.

The year prior, researchers of Tsinghua University in Beijing had expressed the gene for a different iron proteinmembrane channel construct, dubbed MAR, in specific sensory neurons of the nematode worm Caenorhabditis elegans. Applying a magnetic field resulted in changes to the worms movement, they reported in Science Bulletin. All three research groups presented multiple lines of evidence to back up their claims, such as electrophysiologic techniques to monitor the activity of individual neurons in brain slices and in vitro calcium imaging assays, in addition to the behavioral studies.

The studies received a mix reception from the scientific community. Some, like Boston neuroscientist Steve Ramirez, were enthusiastic, calling the work badass on Twitter, while others were skeptical, critiquing the findings in journals and on blogs. That latter includes Markus Meister, a physicist-turned neuroscientist at Caltech, who says hes aware of several research groups that had difficulties replicating some of the findingsspurring some to conduct lengthy, systematic investigations of the function of these constructs.

The new replication studies used a range of methods to investigate whether the constructs work as described in earlier research. In one study, neurophysiologist Tansu Celikel of Radboud University in the Netherlands and his colleagues focused their research on the Magneto construct used in Glers study.

Like Glers group, they used a virus to deliver DNA encoding Magneto to neurons in the mouse cortex and waited two weeks for the cells there to express the construct. Using permanently implanted microelectrodes, they recorded cortical neural activity as they exposed the animals to a magnetic field. The stimulus didnt change the rate of action potentials in those neurons, they observed, and the same was true for in vitro experiments. We argue that the utility of Magneto to control neural activity in vivo is not warranted, the authors write in the preprint.

In the second study, neuroscientist Julius Zhu of the University of Virginia and his team conducted a systematic investigation of all three constructs that had been used in previous studies: Magneto, the TRPV1-ferritin complex developed by the Rockefeller group, and the MAR construct. (Gler, who is also at Virginia provided some materials for the experiments, but the two labs did not collaborate.)

Were anxious to understand what the basis for the differences between his results and ours are.

Jeffrey Friedman, Rockefeller University

Similar to Celikels findings, they observed that magnetic fields did not induce an electrical current in Magneto-expressing mouse hippocampal cells in culture, when the construct was delivered either with a plasmid or a virus. They did note, however, that both Magneto-expressing neurons as well as control cells that lacked the construct frequently displayed spontaneous changes in current that sometimes triggered the cells to fire an action potential. Based on this, they suggest that Glers reportedly magnetically triggered action potentials are likely to represent mismatched spontaneous firings.

The team appears to have had difficulties getting the construct expressed in cells at all. They used a plasmid encoding the Magneto construct to express it human kidney cells in culture, and made electrophysiological recordings of the cells. Neither a magnetic field nor the addition of a protein that stimulates TRPV4 elicited significant electrical currents in the cells. Interestingly, they did observe a current when they repeated these experiments with kidney cells that expressed the wildtype, unaltered version of the gene for TRPV4 expressed separately with ferritins gene. Together with other observations, this suggested that Magneto doesnt form a functional ion channel or incorporate into the plasma membrane, the authors suggest. The construct lacks a portion of the TRPV4 protein considered necessary for its placement in cellular membranes, the researchers note.

In testing the other constructs, Zhus group used viruses to express MAR in neurons from cultured rat hippocampal slices, and the TRPV1-ferritin construct in hypothalamic neurons in intact mouse brains. Again, electrophysiologic recordings did not detect a change in action potentials in any of the genetically modified cells when they were exposed to a magnetic field, although the cells did exhibit frequent spontaneous action potentials. Together, these results support the theoretical conclusion that Magneto, [MAR] and [the ferritin-TRPV1 construct] are incapable of controlling neuronal activity by producing magnetically-evoked action potentials, they write in the preprint. The senior authors of both studies both declined to comment out of concern it would interfere with the publication of their research in a peer-reviewed journal.

What I find most impressive about these reports . . . is just the level of care and effort that has gone into this, remarks Meister. Neither he nor Anikeeva are surprised by the new findings; both have previously critiqued earlier studies. By now, if it worked as advertised, you would expect a small industry of people doing this and using it for all kinds of purposes, Meister says.

Neither have a good alternative explanation for the observations reported in earlier studies. Meister suggests it may boil down to human error, while Anikeeva speculates that tethering ferritin, a relatively bulky protein, to TRPV proteins might possibly make the channels leaky and lower the threshold for action potential firing.

Gler, who developed the Magneto construct, points out several differences between his study and the two preprints that may account for the contradictory results. The groups used different viruses to introduce the constructs to cells, and for the most part, didnt allow as much time for them to be expressed in neurons as Glers group did, which may be why they didnt achieve full presentation in the cellular membranes. For some experiments, they also didnt verify that the viruses were actually expressing the constructs before they introduced them into cells, he adds. Some batches will not work, and you have to systematically make sure that your tools are up to par, he tells The Scientist.

We acknowledge that the system we have developed is a little finnicky in that it requires a lot of optimization to get it to work, he adds. I think that is where the setback is: everybody wants to have something that works immediately. Magnetogenetics techniques will take some time to refine until they are reliable, he says.

Friedman, the senior author of the Nature study, is similarly puzzled why Zhus team couldnt replicate his findings. We take the Zhu paper seriously and . . . were anxious to understand what the basis for the differences between his results and ours are, he says. Zhus team expressed the construct indiscriminately into all neurons in the hypothalamus rather than selectively in a subset of cells, as Friedman did. Some hypothalamic neurons are more easily excitable than others, he explains. Its possible that by restricting the cells we were recording from, we may have gotten a cell type that . . . seems to be more rather than less responsive.

Friedman stresses that his team did multiple experiments as part of their study to ensure that they werent mistakenly attributing spontaneous neural activity to a magnetic effect. For instance, in the same Nature study they repeated their experiments with an altered version of the TRPV1 channel that acts as a chloride channel rather than a calcium channel. Whereas calcium influx would excite a neuron, chloride flux would inhibit it, Friedman explains. We get opposite effects when we use the inhibitory version of the construct instead of the activating one, he says. We wouldnt see that if it was spontaneous activity.

Both Gler and Friedman note there are three additional studies that report having successfully used similar genetic techniques to excite neurons under magnetic fields. In 2017, a team of researchers engineered a construct made of the genes for ferritin and the heat-sensitive channelseither TRPV1 or TRPV4into neural crest cells of chick embryos, claiming to have stimulated the neurons with electromagnetic fields. In 2018, another group combined the TRPV1-ferritin construct with a protein involved in cell migration, and showed that human kidney cells expressing the introduced genes had an unusual migration pattern when under a magnetic field. And earlier this year, a third set of researchers replicated Glers findings by expressing a TRPV4-ferritin construct in a human kidney cell line to better understand its function, also observing a response to magnetic stimulation.

Its not quite clear how these constructs might work. One possibility is that magnetic fields cause the iron atoms in the ferritin to flip periodically, generating heat that causes the temperature-sensitive TRPV1 channel to open. Another option is that the stimulated ferritin would tug open the central pore of the membrane channels. The group that was able to replicate Glers results in kidney cells suggested that the magnetic sensitivity of the TRPV4 channel has more to do with thermal energy than with mechanical force.

Meister has argued that these proposed mechanisms conflict with basic laws of physics, on the grounds that ferritin doesnt have the characteristics necessary to prompt a mechanical stimulus under a magnetic field. In several back-of-the-envelope calculations outlined in his 2016 eLife paper, Meister shows that magnetic interactions between ferritin and a magnetic field would be between five and ten orders of magnitude too weak to generate the mechanical force to cause a membrane channel to open.

The core of ferritin consists not of a truly magnetic substance, but ferrihydrite, which is only weakly paramagnetic at room temperature. This means that the molecule requires a more powerful magnetic field to induce a magnetic momentthat is, to align all iron atoms with the magnetic fieldthan those used in previous studies. Even if the iron ferritin was truly magnetic, the forces would still be too small to account for the proposed mechanisms, notes Anikeeva, who made similar arguments in a separate eLife paper.

Those biophysical arguments could be overcome if physicist Mladen Barbic of the Howard Hughes Medical Institutes Janelia research campus is right. Earlier this year in eLifehe proposed several new alternative mechanisms whereby magnetic stimulation of ferritin could open an ion channel. One, for instance, is based on the Einstein-de-Haas effect, by which iron oxide particles would rotate under a magnetic field, producing energy which could perhaps cause the ion channel to open. Other groups are exploring the possibility of a chemical mechanism through the release of free iron, Friedman says. I think all these are on the table, he says.

The lure of a non-invasive method to control neural activity has kept scholars in pursuit of a reliable method of magnetogenetics, including those that arent based on ferritin. For instance, Anikeevas group has shown that its possible to open TRPV1 and stimulate neuronal activity with synthetic nanoparticles made of the iron oxide magnetite. The particles are known to dissipate heat, and that opens the channels, she explains. However, these particles cant be genetically expressed because they are synthetic. Rather, they have to be injected into the brain.

Another route is to look at organisms in nature that have already evolved systems that respond to magnetic fields. Magnetotactic bacteria, for instance, produce particles similar to the ones Annikeeva synthesized in her lab, she writes. Scientists could also examine the mechanisms that migratory organisms such as pigeons, butterflies, and fish use to sense magnetic fields to navigate, she suggests.

What may help speed these efforts along, and help untangle the controversies around magnetogenetics, is better communication between physics and neuroscience, Anikeeva notes. There should be more interaction between physical and biological sciences, especially in the context of training of both biologists and engineers in each others disciplines and vocabularies.

Katarina Zimmeris a New Yorkbased freelance journalist. Find her on Twitter@katarinazimmer.

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Two Studies Fail to Replicate Magnetogenetics Research - The Scientist

One scientist recently suggested cannibalism might be the way that humanity can survive climate change. We suspect satire, but it seems some of the cells in our bodies are way ahead. Unfortunately, it's the cells we don't want to survive. New research suggests eating other cells could be the secret that allows certain cancer cells to survive the most powerful drugs modern medicine can throw at them.

The side effects of chemotherapy are brutal, but it's an exceptionally effective way to destroy cancer cells while keeping the essential organs of the body alive. Sometimes, however, a small portion of cancer cells manage to evade the chemicals that kill most of their brethren, allowing them to come back, usually with fatal consequences.

Understanding how they do this is key to finding ways to prevent it and saving millions of lives. It's a complex process because not all resistant cancer cells use the same method and we're just starting to understand the diversity of approaches. Dr Crystal Tonnessen-Murray of Tulane University in Louisianna has identified a particularly gory path some breast cancer cells use, which is also adopted by some other cancers.

Despite the great strides that have been made in treating many forms of breast cancer, some have proven more obstinate, including those that have a normal TP53 gene. A normal version of a gene sounds good, particularly considering TP53 codes for a protein that suppresses tumors, and 70 percent of cancers involve mutations in this one gene. However, the other 30 percent of cancers include some with the worst survival rates.

The types of breast cancer Tonnessen-Murray is studying include cells that enter a form of dormancy when exposed to chemotherapy, preventing them from dying, and bounce back when the treatment stops. In the Journal of Cell Biology Tonnessen-Murray reveals that during this stage, known as senescence, the tumor cells often swallow neighboring non-senescent cancer cells.

Tonnessen-Murray has witnessed this occurring in cultured human breast cancer cells, mouse mammary tumors, and certain lung and bone cancers, indicating it could be quite a widespread trait.

The capacity to engulf other cells is an adaptation of processes used by white blood cells to absorb threats such as bacteria for disposal. The consumption of neighbors is associated with longer survival times for these cells, presumably because it provides nutrients to power the cells through the period where normal feeding is interrupted, like lost explorers eating their companions to survive a long winter, and then reboot when the opportunity presents.

"Understanding the properties of these senescent cancer cells that allow their survival after chemotherapy treatment is extremely important," Tonnessen-Murray said in a statement. Exactly how this insight can be used to help those suffering from chemo-resistant tumors remains to be seen, but only by learning these miniature Hannibal Lecters' secrets will we discover how to overcome them.

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Cancer Cells Survive Chemotherapy By Turning Into Cannibals - IFLScience

(Reuters) - For Jessica Lescault there is no question that her 6-year old English bulldog Moose deserves cutting-edge biotechnology cancer treatment as much as any human patient.

Pets are your loved ones, pets should be your family, pets are not something you keep on a chain in the backyard, the intensive-care nurse from Somers, Connecticut, said.

Lescault, 43, who enrolled Moose in a clinical trial of an experimental drug designed to help his immune system fight his cancer, represents the type of pet lover that has spurred animal health companies around the globe to invest in developing complex new treatments previously reserved for humans.

Biotechnology, which produces medicines from living cells, revolutionized the drug industry more than a quarter century ago with breakthrough medicines at prices that now run as high as hundreds of thousands of dollars a year.

In recent years, the cost of genetic testing and biotech drug production has fallen sharply, making biotechnology for pets financially viable at much lower prices, industry experts said. For a FACTBOX, click

Sector leader Zoetis (ZTS.N) and others say animal drug development is faster, less expensive and more predictable than drugs for people.

Its not nearly as common for pivotal studies to fail in animal health as it is in human medicine. Most of them are successful, said Cheryl London, professor in comparative oncology at Cummings School of Veterinary Medicine at Tufts University in Massachusetts.

Biotech drugs for pets, if proven safe and effective, would be a boon to a $44 billion veterinary medicines market currently dominated by vaccines, flea and tick repellents and anti-infectives.

A recent product launch has galvanized the industry.

Cytopoint for canine itch relief sold by Zoetis reached blockbuster status by animal health standards in its second year on the market. Launched in late 2016, Cytopoint generated 2018 sales of $129 million, and first-quarter 2019 sales jumped 65% from a year earlier.

Produced from cloned genetically engineered hamster cells over at least eight bio-processing steps, the monoclonal antibody is no less complex than comparable therapeutic proteins used in human medicine. But the cost to consumers is far less.

Like many biotech drugs, dose and cost is determined by weight. Zoetis declined to disclose its prices. But an animal hospital in Stamford, Connecticut, for example, charges $104 for a 40-pound (18 kg) dog. For much smaller dogs, a Cytopoint injection, which lasts about four to eight weeks, costs about $35 to $50. To keep a large dog from scratching itself raw could run $140 per shot.

The cost of a highly effective new anti-itch biotech drug to treat severe atopic dermatitis in humans can run about $30,000 a year.

Cytopoint was a turning point that has made it clear that (biotech drugs) can be successful in this space, London said. Now there are an estimated five to ten companies developing antibodies for the veterinary market.

That has created increased business for related services.

Its a big challenge for us to keep up with the pace of demand growth, said Klaus Hellmann, managing director at Munich-based Klifovet AG, Europes largest contractor for late-stage clinical trials of veterinary drugs.

While Cytopoint sparked investment interest in biotech treatments for animals, drug development still comes with inherent risks and uncertainty.

Aratana Therapeutics Incs canine lymphoma drug, Blontress, was launched in 2015, but later withdrawn after scientific data led the company to determine it was unlikely to be a financial success.

Declining costs has mitigated some of the risk.

Over the past several years, human health has been able to advance the technology to improve efficiency of their cell production systems, said Rob Polzer, head of global therapeutics research for Zoetis.

Zoetis can repurpose and optimize existing procedures, mechanisms of action and technologies, it said.

The company is seeking approval for a biotech medicine to treat osteoarthritic pain in cats, with plans for a 2021 market launch and a similar product for dogs thereafter.

Others have jumped on the bandwagon.

German start-up Adivo was spun out of biotech firm Morphosys (MORG.DE) in March 2018 out of frustration by its founders that scientific advances for humans were not translating into better treatment options for their dogs.

It has since struck a global collaboration deal with Bayers (BAYGn.DE) animal health unit for its early-stage research platform for animal-specific monoclonal antibodies - the backbone of biotechnology.

Over the last few years, the veterinary market has seen an incredibly dynamic development, said Adivo co-founder Kathrin Ladetzki-Baehs.

This could prove a lifesaver for Moose, the bulldog in the oncology drug trial.

In early August, Lescault discovered a mass on Mooses throat, soon followed by deteriorating health and a diagnosis of canine B-cell lymphoma. Moose was given one to two months to live without treatment or about a year with 25 weeks of punishing chemotherapy.

Lescaults local vet suggested the Tufts trial testing an experimental protein that could help advance the current immuno-oncology craze into the animal health arena.

Tufts declined to disclose the compound or the studys sponsor. But more than three weeks into the trial, Mooses cough and labored breathing has disappeared and he is back to his playful and boisterous self, Lescault said.

While treatment in a clinical trial is free, Lescault said she would not hesitate to pay thousands of dollars for a safe and effective drug to save Moose. I wouldnt blink an eye, she said.

That is exactly what drug companies are banking on.

Additional reporting by Katherine Taylor in Boston; editing by Bill Berkrot

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Biotech is going to the dogs - and big profits await - Reuters

Indian-American oncologist and author Dr Siddhartha Mukherjee, Biocon chairperson Kiran Mazumdar Shaw and Kush Parmar, managing partner at 5AM Ventures, are bringing the innovative Chimeric Antigen Receptor (CAR) T-cell therapy to cancer patients in India. Cell therapies are therapies in which your own body cells are used as drugs to fight cancer. In CAR T-cell therapy, immunological cell is derived from the patients body and weaponised to kill cancer cells in the body.

In an interview to CNBC TV-18, Dr Siddhartha Mukherjee touches upon the affordability of this therapy and the other challenges facing cancer research and treatment in India.

Edited excerpts:

I want to talk to you about your visit to India. There is an announcement you are making with Kiran Mazumdar-Shaw. So tell me a little bit more about that.

We are announcing the formation and launch of a company that will deliver cell therapies in India. Cell therapies are therapies in which cells your own body cells are used as drugs to fight cancer.

One example of this is a so-called CAR T-cell. The name stands for a kind of immune cell, immunological cell that is derived from your own body and is engineered, weaponised to go and kill cancer cells in your body.

This therapy has been in development in many countries for several years but was finally launched as an FDA-approved drug a couple of years ago against certain cancer zones. Different ones work for different cancers but it was not available in India at all. So we, Kiran, Kush Parmar and I partnered up and our goal is to deliver the first in human cellular therapy in India for cancer.

When are we going to be seeing this commercialised?

So, these are extraordinarily complicated. They are called living drugs. They are drugs but they are alive. So you can imagine that producing them, making them available is an extraordinarily complicated process. Also, you have to be extremely careful because it is not like manufacturing aspirin or penicillin. It is taking cells, weaponising them, usually with a virus, and then re-injecting them into the body. So the whole process to develop this, we are hoping, will take about six to eight months. We hope to be in human patients in India within eight months.

Do you have all the regulatory clearances here in India?

A completely new regulatory framework needs to be created so that it is not just free for all as it were because these are toxic therapies, they are reserved for cancer patients, you have to know how to use them. These are living drugs, these are living things. You can imagine that if you dont control them properly, they can go out of control. So you require not just the scientific framework, which is important, but also the regulatory framework. What are the circumstances that an individual hospital or a medical centre can be allowed to use them, what are the safety precautions.

We dont have that yet in India?

We have the broad framework, but it has to be made specific for the use of cellular therapies. India has a very powerful regulatory framework for the use of drugs, but for living drugs, there are some special things that need to be addressed; safety needs to be addressed, you can get contamination. So you cannot just decontaminate a living drug like you decontaminate a chemical.

For instance, just to give you a very practical example, imagine if I am growing a patients T-cells in an incubator and that incubator gets infected with a bacteria or a virus, that whole batch has to be destroyed, the whole incubator has to be cleaned. Maybe the entire facility has to be cleaned to ensure that the next one doesnt get infected. So it is a very different process. It fits under the broad umbrella but it is fundamentally a different process.

It is all going to happen out of Bangalore. How is this going to work?

Kiran and I have had extensive discussions. The best way to do this is to do it at one facility to start with. The closest analogy that we have to living drugs is drug made out of living cells, insulin being one of them. So we decided to start off with a facility where we could have exquisite control. We need to have exquisite control so that we can deliver the therapy to the first needy patients. These are extraordinarily effective drugs, we wouldnt be doing this if these werent extraordinarily effective drugs for particular cancers.

Would these be affordable and accessible?

The challenge is affordability. Just to give you a sense of what the numbers are in the US, there are two T-cell drugs that are now approved in the US and the ticket price for them they are called Yescarta and Kymriah is around $400,000 per person. Part of the problem is that they are intrinsically expensive to make. It is not like making aspirin, it is not like making insulin, it is not like making penicillin. You have to take the cells out of someones body, weaponise them with a virus, grow them in incubators, ensure the safety and then return them back into patients. So I think that the real trick and the real advantage is we will be taking advantage of the ingenuity of Indian engineers and Indian bio-engineers.

We are pretty convinced, we have done very detailed analysis of this. This is my fourth visit and we are confident that we can reduce that $400,000 price tenfold. Even that lies beyond affordability, but it is on the order of a bone marrow transplant in most countries outside the West.

The goal is to make it affordable but this is never going to be an insulin or a penicillin or an aspirin, this is reserved for patients who are very needy, very desperate. We will almost certainly have programmes for the most needy and the most desperate that will allow them to afford it. These are intrinsically very difficult to make.

I want to pick up this latest collaboration that you have with Kiran who is part of the healthcare system in India. You have also got a similar venture where Johnson & Johnson is an investor and that venture you started around three years ago. Do you see more of these collaborations picking up pace? Global pharma has tried to reinvent itself post the backlash that it faced a few years ago. That backlash has now shifted to the technology companies. So do you see more of a collaborative approach being taken and what does it mean for research and development (R&D) going forward?

There is no other option. The maturation of a living drug, the natural cycle is exactly this. So usually drugs are born in laboratories; I am a laboratory investigator, I am a research scientist. I own the patterns that lead to the companies called Vor. I have another one called Myeloid, there are about 6-7 of them. These originate in my ideas or in the ideas of very young investigators who are really driven to solve this problem.

How do you fight cancer with cell or with other therapies? But that is their skillset. Now to convert that into a real therapy, to run a human study to be able to deliver that therapy, safely, effectively to humans, you have to collaborate.

So the way we collaborate now is that we form a biotech company. This company is ceded by investors, its ceded on the basis of science. These investors are extremely savvy, they are extremely thoughtful. Before making an investment, they will make deep analysis of the product itself; is it viable, is it effective, what data do we provide etc. And then you form that company and at that stage you begin to attract companies like Johnson & Johnson, Novartis and open your asset to them, open what you have invented and ask the question would you partner with us in bringing this thing which is just an idea to becoming a real medicine. This is a tried and tested process and this is what is happening.

I know that your research approach has been to understand the micro environment as you call it, to understand cause and co-relation. So given the approach that you have taken and with the likes of Johnson & Johnson, Novartis, Biocon etc. partnering with you, what could it mean for costs? Do you see this becoming more accessible and hence affordable for a country like India?

There is a pipeline process. Part of the reason that I began to collaborate with Kiran was that if we can have one of those most viable telecom and software sectors on the planet, we should be able to make cellular therapies; we should be able to make Chimeric Antigen Receptor (CAR) T-cell, T-cell. There is no fundamental reason that Indian engineers and Indian scientists, and of course, ultimately Indian patients cannot get access to these therapies. This is not like rocket science.

We have mastered that too

We have almost mastered that, but it requires that kind of effort. It requires a certain sense of audacity, it requires an ambition but that is what we are in for. We know the challenges but we have a kind of deep confidence that we can reduce the cost 5-10 fold and still deliver effective therapies. The engineers that I have met here, the scientists that I have met here, the board that we formed is of the bluest chip quality. They involve some of the inventors of these therapies in the United States and in the UK. There is no lack of quality and determination. Operationalising it, making sure that the government partners with us in an appropriate way. Those are the challenges that we are facing right now and we will solve them.

I want to ask you this because you meet people who are backing or funding healthcare. You talk to regulators, you talk to governments around the world. What is the priority, for instance, for the government of India at this point in time? How do you deal with the cancer problem? It is a crisis that this country is also dealing with? What will it take for the government to prioritise it or how should they prioritise it?

The problem of cancer or the crisis of cancer is in some ways the side effect or cross effect of a population that is living longer thats one reason; in India that is compounded by the fact that smoking is still a major problem; cigarette smoking, and pollution is a major problem. We are not effectively vaccinating for cancer such as cervical cancer thats caused by human papillomavirus. Vaccine is available. So there are many arenas in which you could handle the cancer problem but for a government to handle cancer, that strategy is built on a pyramid. The bottom of the pyramid is prevention and that is the deep bottom pyramid.

And that is where there isnt enough attention?

That requires a vast amount of attention and prevention. I gave you some examples, thats why I used those examples first. I used the example of stopping of cigarette and tobacco, the effects of various pollutants particularly in the air and water, and finally vaccination against cancers that can be vaccinated against.

The second layer of that is early detection. This would include finding cancer at the earliest possible phases. The very effective ones are Pap smearing, colonoscopy, less so mammography but still effective to find breast cancer, and in general cancer health screening. The final layer of the pyramid is of course cancer treatments, therapies, including chemotherapy, things like Tamoxifen, which is actually quite inexpensive. Tamoxifen is an inexpensive drug and very effective for breast cancer.

Its important to realise that this pyramid is part of an ecosystem. It feeds back on itself. So you begin with prevention. There is early detection and there is final treatment. You only create a strategy against cancer by creating this entire ecosystem. You dont slice out one piece of it and you certainly dont slice out the most expensive piece of it, which is treatment. Cancer treatment is at the top of the pyramid, the narrowest edge of the pyramid. The base, as far as the government is concerned, is to focus on prevention and that is an important idea for the Indian government and all other governments to internalise. It has done that to some extent. There are now finally anti-smoking, anti-pollution and vaccination campaigns all across India.

But do you see that happening at a pace that will ensure that we are being able to deal with this issue?

So for schizophrenia and depression that process has happened. We now understand very well that schizophrenia is not just a kind of random madness but rather is a genetic disease that has an environmental component to it but has a genes and environment component to it so that is one example.

For schizophrenia, in fact, some of the genes are now being identified and we are trying to understand the circuits, the mental circuits that interact with the environment and thereby cause schizophrenia. We are beginning to understand similarly for depression.

In some cases, it has to do with the destigmatisation of things that were called illnesses, but in fact are not illnesses at all. Homosexuality is one of them. Around 50-70 years ago, a mental health handbook would define homosexuality as a mental illness. It has been a striking mark of progress to understand that that is not the case.

So we have seen a lot of this happen already in many countries. We are seeing that happening in India and it was a very proud moment for the Indian courts to recognise this fact, to recognise that there is biology behind all sorts of health and some things that were called illnesses 20 years ago are really not illnesses, they are states of human behaviour.

What is it that is exciting you in the work that you are doing or the research that you are doing today?

We are doing a lot of work on gene therapy. We have a completely exciting new programme to try to cure a previously incurable form of leukaemia and we are going to run that first in human study next year.

We have invented a new way to try to cure leukaemia, it is the most exciting thing I have ever done in my life and I am basically so anxious to get this study off the ground. It will be the first time that we will get a gene therapy linked cure for leukaemia.

We have a lot of work that we are doing on stem cells. We identified a stem cell that contributes to osteoarthritis, one of the most common diseases of women around the world but also men.

We are doing a lot of work on pancreatic cancer and breast cancer, finding new medicines and again going through this process. I think of myself as an inventor. I invent drugs, all the programmes in my laboratory are now focused on making human medicines. If you are working in my laboratory and you cannot tell me how your work relates to the development of a new human medicine, for me it is a failure. Everything in my laboratory is directed towards absorbing the research from others but trying to make new human medicines.

I was reading this interview that you had done a few years ago where you spoke of how research that was done for prostate cancer came up with ideas on how to deal with breast cancer. So how much of that kind of cross-pollination are you seeing happen?

It is among the richest arenas of cross-pollination going on right now. The word for a person like me is translational scientist. I am a translator. I take insights from basic researchers, people who work on enzymes, bacteria, genes and genetics. I take those insights and ask the question how can I make a human medicine out of that? I take that all the way into a human clinical trial or human clinical study, the invention of the new drug. This can only happen if there is very deep cross-pollination.

Is more of that happening today? Are the two camps more aligned?

The camps have decided to become more aligned because there is no other choice. This is the only way that we know to make medicine move forward. There is a third camp, clinicians, but it is more like a relay race. There is a handoff between the basic scientists of insights to the translation researchers who then hand off that towards the clinicians. Now all of this process has to come together and requires governments to provide regulations. It requires philanthropists. Of course, it requires patients, it requires venture funds. It is a risk-taking process, but nothing moves in the world of science without risk. So all of this has to come together and that is the only way it moves forward.

As you try to get this ecosystem to work together, what is the biggest challenge that you foresee today? Do you see people now reacting differently to the needs of healthcare and putting more money behind research?

We are sort of in that middle of the road and this is the time that requires the most energy because the middle of the road is when people get the most tired. Bill Gates and I have had many conversations together in Seattle, in Davos and other places. The challenges of global health are extraordinarily acute today. They include a vast spectrum from arenas that the Gate Foundation has focused traditionally on, which are contagious or infectious diseases, all the way to chronic non-infectious disease such as hypertension, diabetes, obesity and of cancer.

So, the challenges are great, they are not solved. We are living longer as a population, we now also need to learn to live healthier and we need to learn to live more fulfilling, robust and ultimately more dignified life.

If you are in a particular country in the African continent, maybe your crisis is Ebola. If you are in Seattle, may be you are facing down breast cancer, but the spectrum of disease is vast and is turning out to be quite universal. One interesting statistic which you may not know, and has not been talked about is that in countries where we think most of the deaths are from infectious diseases are slowly turning around. Countries like Tanzania are seeing trends in which the number of deaths from infectious diseases is fewer than the number of deaths from hypertensions or from diabetes or from kidney diseases. So the entire world is experiencing spectra of diseases that range from things that we thought would be sort of flames in one corner but in fact are across the entire world.

Do you see more venture-backed funding, especially when we talk about new therapies, new research?

Biotech has been in the United States, now one of the most attractive arenas, recently. We looked enviously at the tech industry, at the software tech industry and at social media. I have to say, personally I barely use social media, and I have to say social media might have created more ills than it solved. Now it has left biotech to solve those ills or medicines to solve those ills.

I think there has been resurgence of interest in ventures in the biotech world. Medicine has been historically regulated. We have very strong ethical boundaries that we have to abide by and for good reasons because we in the past have violated those ethical boundaries. I think that similar ethical boundaries should have been drawn for all technologies, including social media.

Why are you not on social media at all?

I am on Twitter. It is the only social media that I use and I use it quite sparingly. I dont find using anything less particularly inspiring. I like to talk to people directly. If you very carefully curate as a scientist or a writer, if you very carefully curate who you follow on Twitter, it can be very useful because you can get news. But I like traditional news. I like the long form news and I have never found that joy that some people find in connecting through social media.

Is there another book in the works?

There are two books in the works. Very broadly speaking, one of them will address the history of medicine and the other will address questions of immortality, our search for immortality - digital, social and other.

Has the writing process for you changed? I know that you had rules about how to structure your chapters and so on and so forth? Has it changed over the years?

It has been very much the same. My writing process begins with a lot of research and reading. It begins in a very close space. I need silence, I need a lot of time to think and then it comes out as a work.

How much time do you spend writing every day?

I try to spend at least a couple of hours writing every day, but the writing can be diverse, and they interlock with each other.

You are working on both the books at the same time?

No, but it might involve writing a long letter to a regulator about a clinical study that I am excited about and then switch to the book. Now you could say those are two completely different parts of your brain, but they are not. You see, if every experience that I have becomes fuel for the writing, this interview might find its way into a book. The clinical study that we are doing in leukaemia will almost certainly become a book. What is interesting is that even if it fails, it will become a book. It will become a book about failure. So nothing is off the record in some ways to me in my brain.

What is the one thing that gives you the most hope as we look ahead and what is the one thing that worries you the most?

I think the most hopeful thing is the community of thinkers that exists around the world. I think a vibrant community of thinkers has arisen in India asking vibrant questions.

The more we resist the temptation of groupthink, the more likely we contribute to the world of ideas that is inspiring for me. What is worrisome is just the opposite. What is worrisome is the descent into groupthink.

Recent political developments around the world have not given much hope. People are retiring backwards, towards nostalgic isms driven by fear typically. So what worries me the most is that in 2019 we are living at the end of a cycle of innovation and invention which has been unprecedented in history. If we were to take all these isms and put them on national stages, these isms will inevitably stop the cycle of innovation that we are inheriting. We will not pass it on to our children, we will deny them a generation of invention and innovation and that is a very sad thing. We should be very careful about it.

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CAR T-Cell Therapy May be Available to Cancer Patients in India Next Year: Dr Siddhartha Mukherjee - News18

CAMBRIDGE, England--(BUSINESS WIRE)--Divide & Conquer (D&C), a biotechnology company formed in 2018 with a 10 million (approximately $13.1 million) Series A financing from Medicxi. has left stealth mode to mark the publication of another paper in Nature co-authored by one of its founders, Prof. Frank Winkler of Heidelberg University.

Leveraging Prof. Winklers ground-breaking research published in Nature in 2015 and again this month, Divide & Conquer aims to open a new front in the war on cancer by disrupting the cell-to-cell communication mechanisms of solid tumour cells. The new research shows that the ability of cancer cells to form social networks makes them almost invincible, which is why current drugs fail to cure many patients.

The companys initial focus is on glioblastoma, a lethal form of brain cancer, where cancer cells have been shown to communicate with each other via structures called tumour microtubes.

Co-Founder David Grainger, PhD commented, There is mounting evidence, accumulated over decades, and now taken to the next level in Prof. Winklers papers in Nature, that solid tumours can leverage this network effect to evade all attempts to kill them. We now have compelling evidence that it can be disrupted, with the potential to render the most lethal tumour types curable.

Professor Miroslav Radman, the third co-founder of Divide & Conquer, was one of the first academic scientists to propose that mutation-riddled tumours must share materials between themselves, and with healthy cells, in order to survive and propagate. Bringing together his expertise with that of Prof. Winkler has allowed Divide & Conquer to discover a new class of cancer therapeutics that focus on disrupting these networks.

There is no shortage of biotech start-ups targeting cancer, but this research from Professors Radman and Winkler represents some of the most exciting work in the area that Ive seen, said Moncef Slaoui, PhD, a Director at Divide & Conquer. Glioblastoma is a devastating disease and one of the greatest unmet medical needs. The evidence is now compelling that these networks lie at the heart of this cancers resistance to treatment. At Divide & Conquer we aim to develop new medicines that disrupt such communication between cancer cells and bring these to clinical trials in patients.

Nature is publishing Prof Winklers latest research concurrently with an article on a related topic by a team at Stanford Medicine led by Michelle Monje, MD, PhD, Associate Professor of Neurology and Neuro-Oncology, emphasising the growing body of research in this area.

Dr. Slaoui concluded, Beyond glioblastoma, we envision expanding to other solid tumours such as brain metastasis, the hardest to treat form of breast cancer (so-called triple negative), pancreatic cancer and others. Indeed, we predict that the drugs we develop may be most effective in tumours that are currently the most difficult to treat.

Links

About the Divide & Conquer Founding Team

About Cellular Parabiosis

Cellular parabiosis refers to the ability of individual cells in a tissue to share and exchange contents: ions, small molecules, ribonucleic acid (RNA), proteins, and even whole cell organelles. This cellular solidarity is established via extensions such as tunnelling nanotubes (TNTs) and tumour microtubes (TMs), and transport vehicles such as exosomes, and pores such as gap junctions. Cellular parabiosis allows mutation-riddled tumours to survive and thrive, and even share their toolkit of resistance mechanisms. More information on Cellular Parabiosis is here.

About Divide & Conquer

Divide & Conquer is a biotechnology company focused on discovery and development of a new class of oncology therapeutics aimed at disrupting communication and complementation between cancer cells, also known as cellular parabiosis. The company was founded by David Grainger, PhD, Prof. Miroslav Radman, and Prof. Frank Winkler, and received A-round funding from Medicxi.

Please see conquer.bio for more information, and connect with the company on Twitter and LinkedIn.

About Medicxi

Medicxi is an international investment firm with the mission to create and invest in companies across the full healthcare continuum. Medicxi was established by the former Index Ventures life sciences team and invests in both early stage and late stage therapeutics with a product vision that can fulfill a clear unmet medical need. GlaxoSmithKline, Johnson & Johnson Innovation JJDC, Inc., Novartis and Verily (an Alphabet company) are investors in Medicxi funds.

Medicxis team has been investing in life sciences for over 20 years. Globally, it has invested in 89 innovative biopharma companies and achieved 32 exits through IPO and M&A, including Genmab (NASDAQ Copenhagen: GEN), PanGenetics (sold to AbbVie), Cellzome (sold to GSK), Micromet (sold to Amgen), Molecular Partners (SWX: MOLN), XO1 (sold to Janssen Pharmaceuticals, Inc.), Minerva Neurosciences (NASDAQ: NERV), Padlock Therapeutics (sold to Bristol-Myers Squibb), Gadeta (structured transaction with Gilead), Impact Biomedicines (sold to Celgene), and Adaptive Biotechnologies (NASDAQ: ADPT).

Please see http://www.medicxi.com for more information.

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Divide & Conquer, Developing New Class of Cancer Therapeutics to Disrupt Cell-to-Cell Communication, Emerges from Stealth as New Paper by...

About one in three diabetic patients develops diabetic retinopathy (DR), which can impair vision and lead to blindness. A newstudyinThe American Journal of Pathology, published by Elsevier, provides clear evidence that high glucose increases the levels of enzymatic precursor--lysyl oxidase propeptide (LOX-PP)--that promotes cell death, which was verified in an animal model of diabetes. These findings may help develop novel DR treatments by targeting LOX-PP or its metabolites.

"We found that hyperglycemic and diabetic conditions increased LOX-PP levels," explained lead investigator Sayon Roy, PhD, of the Departments of Medicine and Ophthalmology at Boston University School of Medicine, Boston, MA, USA. "LOX-PP may induce cell death by compromising a cell survival pathway, and in retinas of diabetic rats, increased LOX-PP contributed to retinal vascular cell death associated with DR. Administration of recombinant LOX-PP alone was sufficient to induce cell death. This report shows novel functionality of LOX-PP in mediating cell death under high glucose condition in retinal endothelial cells as well as in diabetic animals."

Studies in pancreatic and breast cancer cells suggest that LOX-PP overexpression may trigger cell death. The researchers therefore studied the role of LOX-PP in the retinal tissue. The retinal blood vessels of normal and diabetic rats and normal rats administered artificially synthesized LOX-PP (recombinant LOX-PP, rLOX-PP) directly into the eye, were examined. Changes associated with DR such as swelling, blood vessel leakage, blockage or thickening of vascular walls, and histologic indicators such as acellular capillaries (AC) and pericyte loss (PL) were studied.

More AC and PL were observed in the retinas of diabetic rats compared to controls. In non-diabetic rats, injection of rLOX-PP directly into the eye also increased the number of ACs and PLs compared to rats receiving a control injection.

The effect of high glucose on retinal endothelial cells grown in culture was also studied. Adding glucose to the cell cultures up-regulated LOX-PP expression and reduced AKT (protein kinase B) activation. Cells exposed to rLOX-PP alone exhibited increased cell death along with decreased AKT phosphorylation. The present study provides clear evidence that high glucose increases LOX-PP levels, which in turn promotes cell death. Furthermore, LOX-PP appears to induce cell death by compromising a pathway involved in cell survival.

"DR is the leading cause of blindness in the working age population," noted Dr. Roy. "Unfortunately, there is no cure for this devastating ocular complication. Our findings suggest a novel mechanism for high glucose-induced cell death involving LOX-PP, which may be a therapeutic target in preventing retinal vascular cell loss associated with DR."

LOX is an extracellular enzyme responsible for cross-linking collagen and elastin molecules to form a stable extracellular matrix. The role of the LOX propeptide, LOX-PP, is less understood, although it may play a role in keeping LOX in an inactive state.

Reference: Kim, et al. (2019) Effects of High GlucoseInduced Lysyl Oxidase Propeptide on Retinal Endothelial Cell Survival: Implications for Diabetic Retinopathy.The American Journal of PathologyDOI:https://doi.org/10.1016/j.ajpath.2019.06.004

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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A Potential Drug Target for Diabetic Retinopathy - Technology Networks

As of Sept. 1, Kara Sawarynski, Ph.D., has been continuing to tap the problem-solving/critical thinking skills she developed as an academic throughout her education and career, but in a new capacity as the vice chair of Foundational Medical Studies at Oakland University William Beaumont School of Medicine.

As vice chair, her primary responsibilities are to support the departments ongoing development of research programs, assist the chair in promoting faculty development and collaborations, and serve as a sounding board for faculty ideas and issues. She hopes to use her substantial connections at both Oakland University and Beaumont Health, to help foster Foundational Medical Studies strategic mission and goals.

Sawarynski said shes excited about the opportunity and plans to begin by learning more about her colleagues what their respective strengths are, and what their goals are with respect to careers and research.

I really hope to offer assistance and help build connections between shared interests that might be undiscovered, so that I can help others succeed, she said.

Sawarynski joined the Department of Foundational Medical Studies as a full-time faculty member in 2012. Sawarynski, a recently tenured associate professor, will continue teaching cell biology in the basic science courses, as well as co-directing the Embark research program.

Sawarynski received her bachelor of science degree in Biomedical Sciences from the Lee Honors College of Western Michigan University. She completed her doctoral work in cancer biology at Wayne State University School of Medicine and the Barbara Ann Karmanos Cancer Institute.

When Sawarynski completed her work at Karmanos, she started working as a research associate at William Beaumont Hospital in Royal Oak, in the infectious disease lab of Matt Sims, M.D., director of Infections Disease Research, Beaumont Health, and OUWB professor.

While still at Beaumont, Sawarynski became an adjunct assistant professor in the Department of Biomedical Sciences (since changed to the Department of Foundational Medical Studies) and was involved with helping to plan the basic science curriculum. She also taught some of the schools first sessions to its charter class in 2011.

Finding her passion as an educatorSawarynski said it didnt take her long to realize how much she liked being an educator. After the inaugural OUWB class completed its first year, Sawarynski made the move to OUWB on a full-time basis as a tenure-track assistant professor.

I love research and I love everything that comes with it, she said, noting her research career has included molecular and cellular biology, cancer biology, infectious diseases (and now medical education techniques).

But the bacteria youre working with (in research) doesnt talk back to you, Sawarynski said. Being a people person, I realized its a lot more fun engaging with students. I also came to realize how fulfilling it can be.

Thats why she also finds it rewarding to be co-director of OUWBs Embark research program an OUWB required scholarly concentration that provides a mentored introduction to research and scholarship. The four-year longitudinal curriculum consists of structured coursework in research design and implementation, compliance training, research communication, and scholarly presentation, with protected time to develop mentored projects in a wide-range of community and health-related settings.

Sawarynskis responsibilities include development and implementation of the longitudinal research design courses, directing of the first year through fourth year medical students in the conception and execution of their required independent research projects, and oversight on Embark program events.

Its so energizing to not necessarily be a specific expert in all of the fields students are trying to research, but help them look at specific problems and analyze them, Sawarynski said. I enjoy helping them realize that while there can be frustrating aspects of what theyre doing, they gain from every experience.

With regard to her work as a department vice chair, Sawarynski said she plans to begin by learning more about her colleagues what their respective strengths are, and what their goals are with respect to careers and research.

Sawarynski said that its an exciting time at the school as it moves into its next phase.

Someone says You know, I have this idea and I start brainstorming. I think about all the different ways that we could think about the idea, or how to attack different goals, she said We can really start to look for ways to involve the mission of the school, our own experiences and expertise, and look for ways to work together to do some pretty cool things.

For more information, contact Andrew Dietderich, marketing writer, OUWB, atadietderich@oakland.edu.

Follow OUWB on Facebook, Twitter, and Instagram.

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New vice chair named for OUWB Department of Foundational Medical Studies - News at OU

Scientists have discovered a compound could help slow down pancreatic cancer by targeting proteins that promote metastatic cells.

Researchers at Johns Hopkins Medicine found that the compound, 4-HAP, reduced tumors in mice and could improve survival for pancreatic cancer patients.

According to the National Cancer Institute, 73,554 people in the U.S. have pancreatic cancer and only 9.3 percent of those diagnosed survive five or more years.

The study, published in the journal Cancer Research, examined two types of proteins, mechanoresponsive proteins and non-mechanoresponsive proteins.

Scientists looked at a total of seven proteins, including nonmuscle myosin IIA, IIB and IIC; alpha-actinin 1 and 4; and filamin A and B. The mechanoresponsive proteins IIA, IIC, active actinin 4 and filamin B increased cancer tissue in the pancreas by over-producing the cancer cells.

Scientists found that even though the protein nonmuscle myosin IIC was found to be low in the cancer cells it had a profound impact on the cell's overall function. When they exposed these proteins to 4-HAP, it increased the cells' overall structure and stiffened the cells.

The group then tested 4-HAP as a treatment for pancreatic cancer by using a mouse model that had human pancreatic tissue implanted in the mouse's liver. They found that the tumors reduced by 50 percent.Researchers believe that treating the cells with the compound will allow scientists to target cancerous cells while protecting the healthy cells in the pancreas.

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A compound may improve pancreatic cancer survival rate, scientists find - PhillyVoice.com

Photo: Reuters

JOHANNESBURG - After the establishment of the new constitution of the US, Benjamin Franklin wrote a letter in 1789 stating that nothing in this world is certain, except death and taxes. But now it seems that some scientists are not that sure about death anymore.

For a long time people have strived to live longer with the result that one of the important medical frontiers today is to extend the human lifespan. In June 2018, the World Health Organisation published the 11th edition of its International classification of diseases, which contained a seemingly insignificant new addition, namely, Code MG2A: Old age.

However, this minute inscription could be one of the most important inclusions in human history and could potentially lead to the development of new drugs designed to treat one of the worlds most universal ailments ageing, which has been known as a major contributing cause to most other age related illnesses.

Although regulatory changes will be necessary, this new approach to ageing would make it possible for medical doctors to eventually prescribe medicines to slow the condition of ageing and ultimately death.

Notwithstanding the absence of the necessary regulatory environment, bio-medical research has been making considerable progress over the past few years. Since Clive McCay discovered in 1934 that the restriction of caloric intake through limited diets extended the live of rats, Michael Rose from the University of California, Irvine, in 1981 bred a strain of fruit fly that can live four times longer than normal.

In 1993 Cynthia Kenyon and her team from the University of San Francisco discovered the daf-2 mutation, which doubled the life span of roundworms (nematodes).

In addition to numerous genetic studies, it was inevitable that drugs would be developed to slow ageing and extend human life. In 2006 Matt Kaeberlein from the University of Washington, demonstrated that rapamycin a drug isolated from soil bacteria on Easter Island could increase the life span of yeast cells. It was later proven that rapamycin increases the life span of mice by 24percent.

In 2016 Nir Barzilai, director of the Institute for Ageing Research at the Albert Einstein College of Medicine discovered that metformin, could prolong the life span of silkworms. Metformin (marketed under the trade name Glucophage) is a well-known and effective first-line medication used by millions of people with type 2 diabetes.

Over the last five years researchers discovered that this now inexpensive generic and widely available drug influences several metabolic and cellular processes closely associated with the development of age-related conditions. Except for metformins lowering of glucose levels, it also has an effect on inflammation, ameliorates DNA and cellular damage, improves muscle tissue health, preserve cognitive function, and reduce mortality.

The reduction of chronic damage resulting from inflammation eventually could have positive benefits for ageing, cardiovascular disease, Alzheimers disease and cancer.

Numerous animal studies have proved that metformin may delay the ageing process and have a neuroprotective role. Therefore Barzilai and his team are taking their research one step further to demonstrate metformins ability in humans to delay the onset of comorbidities related to ageing, thereby reducing the period of morbidity at the end of life and increasing the health span of people.

Dr Tze Pin Ng and colleagues from the National University of Singapore published their research in The Journal of Alzheimer disease, indicating that metformin was inversely associated with cognitive impairment.

After reviewing thousands of medical records, Dr Scherrer form Saint Louis University in June 2019 published an article showing that African Americans older than 50 years and treated with metformin had a much lower risk for dementia. It is thus becoming clear that metformin could play an important role in deferring the onset of Alzheimers disease and dementia.

In an observational study Dr Bannister from Cardiff University found patients with type 2 diabetes treated with metformin monotherapy lived significantly longer than patients treated with alternative medicine or even a large control group without diabetes or medication. This research implies that metformin may have benefits even for non-diabetes.

However, despite all the benefits of metformin, we are still years away from being able to state with absolute confidence that metformin prevents ageing.

Numerous new start-ups are currently searching for life extending drugs, such as the biopharmaceutical company resTORbio that is researching a drug known to enhance immunity against age-related viral infections. The same drug may in fact also prevent numerous other manifestations of ageing.

Calico (an acronym for California Life Company) is a secretive biotech company in the USA that is a division of Alphabet (the Google parent company). Although the company states that they focus on health and wellbeing and the challenge of ageing, it is well known that according to Art Levinson, the chief executive, the mission of the company is in fact to achieve human immortality. The company therefore researches therapies for age-related illnesses in an attempt to extend human life span.

In November last year Calico hired Dr Garret FitzGerald, an Irish professor, who is an expert on molecular clocks or the idea that genes operate on 24-hour cycles, which could be altered to slow down cell damage and delay Alzheimers.

The California start-up Unity Biotechnology is researching drugs that could remove the zombie-like cells that accumulate with age, while CohBar is attempting to harness the power of mitochondria-based therapeutics aimed at slowing ageings effects.

A research team from Mayo, Wake Forest and the University of Texas, San Antonio, recently announced promising results from early human trials with senolytics agents that selectively destroy senescent cells or induce cell death.

The researchers claimed that they were able to stop Alzheimers disease in it tracks.

Without doubt, anti-ageing medicines are now amongst the top ten disruptive innovations. Contrary to popular belief, there is no biological law that determines that people must age. Ageing is currently the biggest risk factor behind most of the age-related diseases. Quite often when one disease in older people is addressed through treatment and it improves, another disease will often replace it, unless ageing itself is targeted.

Ageing research is therefore focusing not only on extending human life, but the eradication of disease itself.

Although the processes for extending life are complicated, the metformin research has shown that sometimes it may be as simple as repurposing medications that are already available and affordable.

If we ask a person to point out persons who are 70 years old it is quite easy, since we all know the biology of ageing. But to think that it is normal and that we cannot do anything about it, is an error.

Research shows that we can intervene in ageing, even in the later phases. People 50 years or older most probably have a brighter future since it is possible that they would not be ageing as fast or poorly as their parents.

Over the years cosmetic companies have through clever marketing convinced women to buy moisturisers and other anti-ageing cosmetics. Most pharmacies would have at least fifty or more products that falsely claim to be anti-ageing.

Unfortunately most creams achieve very little and the vitamins only give users expensive urine. Currently this market is worth hundreds of billions of rand per year. Just imagine how much a pill that could really slow ageing or stop death could be worth. In the era of the fourth industrial revolution nothing seems to be impossible everything could be hacked, including the human body.

Although some people might frown on the possibility of a tablet extending human life, the situation is not unfamiliar. Before Louis Pasteur enlightened the world with his germ theory in the 1880s, people believed death by disease was inevitable.

The discovery of penicillin in 1928 totally changed this believe. So why not envisage a time in the future when scientists could stop ageing and age-related illnesses and offer a better quality of life? Economically it would bring welcome relieve to overextended healthcare services and the ill-planned National Health Insurance of South Africa.

The technologies being developed now would not only give us extra years of life, but also extra years of youth.

In the years to come we will begin to understand that ageing is something that can be reversed.

Whether we will live long enough to benefit from innovation in this sector or be the last generation to live a relatively short life depends on current innovation, human trials and regulatory changes to make it possible.

Perhaps, it is indeed time that we start treating age as a disease.

Professor Louis C H Fourie is a futurist and technology strategist.

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OPINION: Bid to stop ageing - research continues - IOL