Stem Cell Clinic

#E#ECTRIMS2019 – In Progressive MS, ATA188 Showing Safety and Hints of Effectiveness in Phase 1 Trial – Multiple Sclerosis News Today

People with progressive forms of multiple sclerosis (MS) and past exposure to the Epstein-Barr virus are responding to a potentialimmunotherapy known as ATA188, tolerating the treatment well and with signs that suggest effectiveness, early updated data from an ongoing Phase 1 trial show.

The research, Preliminary safety and efficacy of ATA188, a pre-manufactured, unrelated donor (off-the-shelf, allogeneic) Epstein-Barr virus-targeted T-cell immunotherapy for patients with progressive forms of multiple sclerosis, was presented at the 35thCongress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)held in Stockholm (Sept. 1113).

Infection with the Epstein-Barr virus (EBV)is linked to a greater susceptibility to MS. EBV promotes the expansion of immune B-cells, which can produce autoantibodies against myelin, the protective coating of nerve fibers that is progressively damaged in this disease.

People with MS are believed to be deficient in T-cells, which would normally kill EBV-infected B-cells.

ATA188, byAtara Biotherapeutics, is designed to overcome this deficiency by providing allogeneic immune T-cells that target EBV in B-cells. (Allogeneic cells are from donors with no family or genetic relationship to the recipient; an advantage is that these cells are available immediately, or off-the-shelf.)

The Phase 1 study (NCT03283826), taking place in the U.S. and Australia, is assessing the safety and efficacy of ATA188 in progressive MS patents here, a near equal mix of secondary progressive disease (SPMS) and primary progressive MS (PPMS) ages 18 to 66. Patients are assigned to four groups, each testing a different cell dose: 5 x 106, 1 x 107, 2 x 107, and 4 x 107.

Clinically recognized MS scales are assessing ATA188 effectiveness at baseline (study start), and at roughly 3, 6, and 12 months after initial treatment. These include the Expanded Disability Status Scale(EDSS), the Fatigue Severity Score, the MS Impact Scale, the Timed 25-Foot Walk (T25FW) where patients walk 25 feet as quickly and safely as possible the 9-Hole Peg Test of hand and finger skills, 12-Item MS Walking Scale, and tests of visual acuity.

Early data previously reportedshowed that treatment with ATA188 was well-tolerated across the four groups, with no evidence of cytokine release syndrome(a form of systemic inflammatory response), graft versus host disease(which refers to the attack of the hosts cells by transplanted stem cells), or dose-limiting toxicities.

Preliminary data now reported at ECTRIMS, collected through July 29, 2019, covered the four groups of six patients each (median age, 56).

Results found no dose-limiting toxicities. There were also no reports ofclinically significant laboratory abnormalities in any of the groups.

One patient in group 4 (using 4 x 107cells) dropped out of the study due to aMS relapse that took place in the setting of an ongoing URI [upper respiratory tract infection] and possible dental infection, the researchers reported at ECTRIMS.

Safety results showed that across the four planned dose cohorts, ATA188 was well tolerated in patients with progressive forms of MS, with no evidence of cytokine release syndrome, graft versus host disease, or dose-limiting toxicities, they added.

Efficacy data were available from the first two groups, and hints of benefit were seen.

Four of the six patients in group 1 the lowest dose group showed clinical decline at 6 and 12 months, defined as worsening in two or moreMS scales compared to baseline. The other two showed at least partial improvement in these scales at month six, with one of these showing stable disease at 12 months.

In group 2 (1 x 107),all six patients showed either clinical improvement (two people) or partial clinical improvement (four people) at six months, or improvements in two or more or more MS scales. Data for this group did not stretch out 12 months.

Better results in terms of lesser disability were seen in people in group 2, where only one person experienced clinical decline compared to four of the six patients in group 1.

These preliminary results support continuing the trial to identify the dose for both the OLE [open-label extension] and the randomized, double-blind, placebo-controlled portion (part 2) of the study, the researchers wrote.

I am encouraged by the well tolerated safety profile, as well as early findings of potential efficacy in the ongoing ATA188 Phase 1 study, Amit Bar-Or, MD, a principal investigator in the trial and chief of MS Divisionat thePerelman School of Medicine at the University of Pennsylvania, said in apress release.

He also favored this studys innovative approach, that of using multiple MS scales to measure benefit.

I look forward to advancing the study alongside my colleagues for progressive MS patients who have limited treatment options,and where continual clinical decline is expected, Bar-Or added.

These early data support the potential of a T-cell immunotherapy targeting EBV-infected B-cells in progressive MS, said AJ Joshi, MD, Ataras senior vice president and chief medical officer.

Our recent completion of enrollment in the fourth and final dose escalation cohort moves us closer to identifying the dose to be used in the studys placebo-controlled Phase 1b part, Joshi added.We are committed to advancing ATA188 for MS patients, and look forward to presenting additional efficacy and safety results from this study in 2020, including from cohorts 3 and 4.

Of note, eight of the studys 14 authors are employees and stockholders of Atara. One other is a member of the companys Neurology Clinical Advisory Panel.

Jos is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has studied Biochemistry also at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario, in London, Ontario. His work ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimers disease.

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Patrcia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

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#E#ECTRIMS2019 - In Progressive MS, ATA188 Showing Safety and Hints of Effectiveness in Phase 1 Trial - Multiple Sclerosis News Today

Researchers Develop New Class of Lung Cancer Drugs – PharmaLive

Working with a new class of cancer drugs called G12C KRAS inhibitors, researchers at the Francis Crick Institute and The Institute of Cancer Research (ICR), London, developed drug combinations to stay ahead of drug resistant tumors. They published their research in the journal Science Translational Medicine.

Cancer cells often develop resistance to drug treatments. Many are initially susceptible to chemotherapy, but over time develop resistance, causing researchers to work to develop new drugs that attack the cancer by way of different mechanisms or to find combination therapies that simultaneously kill the cells in different ways.

Mutations in the KRAS gene are found in 14% of lung adenocarcinomas, which is the most common type of lung cancer. It is a particularly deadly form with few if any effective treatments for most patients. About eight out of 10 patients die within five years of diagnosis. In the UK alone, about 2,800 people are diagnosed with lung cancers with the G12C KRAS mutation.

Lung adenocarcinoma is a type of non-small cell lung cancer. NSCLCs make up 80% of lung cancers, and of these about 50% are adenocarcinomas. It is the most common lung cancer in women, Asians and individuals under the age of 45. It is also, unexpectedly, more common in non-smokers than people who currently smoke. Contributing factors are genetics, secondhand smoke, and radon exposure.

Its likely that tumors will develop resistance to the new drugs, so we need to stay one step ahead, said Julian Downward, senior author of the study who led the research. We found a three-drug combination that significantly shrank lung tumors in mice and human cancer cells.

Downward added, Tumors treated with the combination shrank and stayed small, whereas those treated with the G12C KRAS inhibitor alone tended to shrink at first but then start growing again after a couple of weeks. Our results suggest that it would be worth trying this combination in human trials in the coming years, to prevent or at least delay drug resistance.

The other two drugs in the cocktail block the mTOR and IGF1R pathways, which had previously been tested in cancer patients. There are mTOR inhibitors on the market, such as rapamycin and temsirolimus (Pfizers Torisel). Currently, IGF1R inhibitors are experimental drugs in the clinical trial stage.

The researchers utilize cancer cells from patients with the G12C KRAS mutation, which they then edited to block the activity of 16,019 different genes. They then treated the edited cells with drugs that KRAS mutational cancer typically respond to.

We found that cell lines without the MTOR gene were significantly more vulnerable to both KRAS and IGF1R inhibitors, said Miriam Molina-Arcas, senior laboratory research scientist at the Crick. When we blocked all three pathways, the mutant cancer cells were simply unable to survive. This makes it a promising avenue for human trials in the coming years, although this is still early research. Promising results in mice and cells can tell us whats worth trying, but its impossible to predict how patients will respond until we actually try.

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Researchers Develop New Class of Lung Cancer Drugs - PharmaLive

Factbox: Animal health sector aims to emulate Zoetis biotech leap – Reuters

FILE PHOTO: Moose, a six-year-old English Bulldog with B-cell lymphoma, receives trial medical treatment at the Tufts Veterinary Medical School by vet technicians Stephanie Pollen (L) and Michele Willett in North Grafton, Massachusetts, U.S., September 13, 2019. REUTERS/Katherine Taylor

(Reuters) - A commercial breakthrough in the field of complex therapeutic proteins for dogs by sector leader Zoetis (ZTS.N) has roused rivals to action in a hunt for biotechnology medicines to treat pets.

Previously reserved for humans, biotech drugs made from genetically engineered living cells are now seen as ripe for the pet health market. The following are some of the recent deals, launches and development projects in the space:

- British animal health company Dechra Pharmaceuticals Inc (DPH.L) agreed to a deal https://www.akstonbio.com in August to utilize development work by U.S. insulin specialist Akston Biosciences for a once weekly shot for diabetic dogs to replace daily injections, with a view to expanding the collaboration to cats. Dechra has said long-acting insulin, which is typically produced from genetically modified bacteria, should become its biggest product.

- U.S. animal health company Kindred Biosciences Inc (KIN.O), which repurposed a human antidepressant to stimulate appetite in underweight cats, has several genetically engineered biologic drugs under development kindredbio.com/pipeline, targeting diseases such as dermatitis in dogs and anemia in cats.

- German early-stage biotech research firm Adivo in April signed a global collaboration deal here with Bayer's (BAYGn.DE) animal health unit a little over a year after Adivo was spun out of human biotech firm Morphosys (MORG.DE) with a mission to develop antibodies for dogs.

- Privately-held German drugmaker Boehringer Ingelheim, the global No. 2 in animal health, in April launched here the first stem cell-based veterinary medicine to treat lameness in horses caused by inflamed joints, a common worry for both recreational and competitive riders.

- Industry leader Zoetis Inc (ZTS.N), which has a successful anti-itch biotech drug for dogs on the market, said here in August it was seeking approval for more antibodies, targeting osteoarthritic pain in cats with plans for a 2021 market launch, drawing on its 2017 acquisition of Nexvet Biopharma. A similar product for dogs is also in the pipeline.

- In June of 2018, Zoetis signed a deal here with human biotech firm Regeneron Pharmaceuticals Inc (REGN.O) to adopt its antibody technology for animals, targeting inflammatory disease and cancer.

Reporting by Ludwig Burger; Edited by Bill Berkrot

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Factbox: Animal health sector aims to emulate Zoetis biotech leap - Reuters

Only hearts harvested from living babies can be used for research, expert tells Daleiden hearing – Lifesite

SAN FRANCISCO, California, September 19, 2019 (LifeSiteNews) An expert in adult stem cell research told a San Francisco court Wednesday that fetal hearts used in research are harvested from living babies.

Dr. Theresa Deisher testified on the last day of the criminal preliminary hearing of David Daleiden and Sandra Merritt that had stretched into three weeks.

The investigative journalists from the Center for Medical Progress (CMP) are charged with 14 felony counts of taping confidential information without consent in connection with the undercover videos CMP released in 2015 exposing Planned Parenthood trafficking in baby body parts.

Public outrage over the groundbreaking videos prompted congressional hearings and calls for the federal defunding of Planned Parenthood.

Daleiden and Merritt are claiming a Section 633.5 defense that allows covert taping when investigating violent crimes. Their lawyers are also arguing the law does not consider as confidential conversations that have a reasonable expectation of being overheard.

A focus of Daleidens early research, a key element in the defenses case and a source of public debate during the hearing, is a 2012 Stanford University study that used human baby hearts supplied by the fetal organ harvesting company StemExpress in a Langendorff apparatus.

Daleiden testified that Deisher was one of the experts he consulted in 2012 about whether the hearts used in the study were harvested from living babies, and Deisher told him that was the case.

She confirmed that in her testimony Wednesday as a defense expert witness.

Deisher, who holds a Ph.D. in Molecular and Cellular Physiology from Stanford University School of Medicine, told the court that a heart requires energy to relax after contracting, and if it contracts after it runs out of energy, it is useless for research.

Once the heart goes into contraction, you cant get it to come out of that position, she told the court.

To be harvested, a heart has to be beating and be arrested in a relaxed position by perfusing it with a potassium solution, she told the court.

The relaxed heart is then transported to the research site, where it is started again electrically, Deisher said.

So to be used in theLangendorff apparatus, the fetal heart would have to be alive when dissected from the fetus? asked Daleidens lawyer Brentford Ferreira.

It has to be beating and immediately go on the Langendorff, Deisher said, or be arrested in a relaxed state while it was still beating and subsequently put on a Langendorff.

Deisher testified that according to scientific protocol, the 2012 Stanford studys citing of StemExpress meant the company supplied the human hearts.

She said Daleiden first called her in 2010 when he learned about the harvesting and selling of aborted baby body parts.

Deisher said she told him then that the most horrific thing about the trafficking in baby body parts was that some of the babies had to have beating hearts when they were harvested.

Between 2010 and 2013, Daleiden called her several times. He wanted to know what a Langendorff was and the vocabulary of stem cell research, she said. I just taught him the science.

Deisher said she is the founder and CEO of a company in Seattle that is developing alternative research methods to eliminate human exploitation in medical research. Her website bio says she is the first person to discover adult stem cells.

She testified that its never necessary to use fetal organs for stem cell research, because there are induced pluripotent stem cells available, which are produced from adult stem cells and can be cultured into any type of body cell.

Deisher said convenience and pressure from animal rights activists motivate researchers to use human fetal organs.

Deputy Attorney General Johnette Jauron asked Deisher if she consulted with Daleiden about his undercover operation before he began the 30-month project.

Deisher said she hadnt heard of CMP until the videos were released and that she only watched them much later.

Judge Christopher Hite also questioned Deisher, asking her if she ever discussed Daleidens undercover investigations with him or any of the Does, if she had performed abortions or worked at a fetal tissue procurement company, or was familiar with abortion techniques. Deisher said no to all questions.

Daleiden and Ferreira lauded Deishers testimony.

I thought it was riveting, especially when she talked about the horror of babies being born alive and having their hearts being torn out of their little bodies,Ferreira said.

Deishers testimony shows why I and my colleagues like Sandra Merritt and others did our undercover work with the Center for Medical Progress, Daleiden told LifeSiteNews.

Because theres very compelling evidence that the most valuable organs and tissues from aborted children are harvested from aborted children while theyre still alive, he said.

Those kids are actually killed through vivisection and that is a human atrocity that has to be exposed.

Deisher reiterated later to LifeSiteNews that in order to obtain a heart for a Langendorff apparatus, the organ harvesters would cut open the babys chest and they would take the heart out beating and drop it in a buffer with potassium.

It would then be transported in a vial with pre-oxygenated buffers and other preservatives to the research site.

Anyone involved in the field would know this is the case.

Of course, if the heart isnt beating, they cant get any of these cells, its impossible, technologically impossible, she said. Nobody wants a stopped heart.

The whole process is beneath the dignity of a civilized society, to cannibalize the bodies of aborted babies, to harvest from a living baby. Theyre not even anesthetized. We dont even do that to mice and rats, Deisher told LifeSiteNews.

Theres no scientific or medical reason that we need to do that and anyone who claims it either does not understand the full science or theyre not telling the truth, she said.

She believes the charges against Daleiden and Merritt will be dropped.

If they dont dismiss the charges, then theyre not following the law, Deisher said.

He was investigating based on the fact that I told him that babies were being harvested alive. Thats a crime, and undercover investigation is, if I understand from what the lawyers told me, perfectly legal if you think theres a crime thats occurring.

Read all LifeSiteNews coverage of Daleiden and Merritts preliminary hearing here.

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Only hearts harvested from living babies can be used for research, expert tells Daleiden hearing - Lifesite

CRISPR/Cas9 Potential in Advancing Parkinson’s Understanding and Treatment Focus of Review Study – Parkinson’s News Today

In a recent review, scientists highlight the potential of gene editing technologies like CRISPR/Cas9 to not only understand the molecular mechanisms behind Parkinsons disease, but also identify new targets for treatment.

The review study, Interrogating Parkinsons disease associated redox targets: Potential application of CRISPR editing, was published in the journal Free Radical Biology and Medicine.

One of the hallmarks of PD is the loss of dopamine-producing neurons in the substantia nigra a brain region involved in the control of voluntary movements, and one of the most affected in PD. This occurs due to the clustering of a protein called alpha-synuclein in structures commonly known as Lewy bodies inside neurons.

Parkinsons is complex and multifactorial disease, with both genetic and environmental factors playing a role in either triggering or exacerbating the disease.

Genetic causes can explain 10% of all cases of PD called familial PD , meaning that in the majority of the cases (sporadic PD) there is an interplay between genetics and environmental risk factors.

Researchers atSechenov Universityin Russia and theUniversity of Pittsburgh reviewed the role of metabolic pathways, especially problems with mitochondria cells powerhouses and iron accumulation, as well as mechanisms in cell death (called apoptosis and ferroptosis) in the development and progression of Parkinsons disease.

These processes were discussed in the context of genome editing technologies, namely CRISPR/Cas9 a technique that allows scientists to edit genomes, inserting or deleting DNA sequences, with precision, efficiency and flexibility.

CRISPR is a promising technology, a strategy to find new effective treatments to neurodegenerative diseases, Margarita Artyukhova, a student at the Institute for Regenerative Medicineat Sechenov and the study first author, said in a press release.

Mitochondria dont work as they should in people withPD, resulting in shortages of cellular energy that cause neurons to fail and ultimately die, particularlydopamine-producing neurons. Faulty mitochondria are also linked to the abnormal production of reactive oxygen species, leading to oxidative stressan imbalance between the production of free radicals and the ability of cells to detoxify them that also damages cells over time.

Because mitochondrial dysfunction is harmful, damaged mitochondria are usually eliminated (literally, consumed and expelled) in a process called mitophagy an important cleansing process in which two genes, called PINK1 and PRKN, play crucialroles. Harmful changes in mitophagy regulation is linked with neurodegeneration in Parkinsons.

Previous studies with animal models carrying mutations in the PINK1and PRKNgenes showed that these animals developed typical features of PD mitochondrial dysfunction, muscle degeneration, and a marked loss of dopamine-producing neurons.

PINK1codes for an enzyme that protects brain cells against oxidative stress, whilePRKNcodes for a protein called parkin. Both are essential for proper mitochondrial function and recycling by mitophagy. Mutations in both the PINK1 and PRKNgene have been linked with early-onset PD.

However, new research suggests that the role of PINK1 and PRKNin Parkinsons could be more complex and involve other genes likePARK7(DJ-1), SNCA (alpha-synuclein) andFBXO7 as well as a fat molecule called cardiolipin.

CRISPR/Cas9 genome editing technology may be used to help assess the role of different genetic players in Parkinsons disease, and to look for unknown genes associated with disease progression and development. Moreover, this technology can help generate animal and cellular models that might help scientists decipher the role of certain proteins in Parkinsons and discover potential new treatment targets.

Iron is another important metabolic cue in Parkinsons. While its essential for normal physiological functions, excessive levels of iron can be toxic and lead to the death of dopamine-producing neurons in the substantia nigra.

Iron may also interact with dopamine, promoting the production of toxic molecules that damage mitochondria and cause alpha-synuclein buildup within neurons.

CRISPR/Cas9 technology can be used to help dissect the role of proteins involved in iron transport inside neurons, which in turn may aid in designing therapies to restore iron levels to normal in the context of Parkinsons disease.

Finally, researchers summarized evidence related to the role of two cell death pathways ferroptosis and apoptosis in PD. Ferroptosis is an iron-dependent cell death mechanism by which iron changes fat (lipid) molecules, turning them toxic to neurons. This process has been implicated in cell death associated with degenerative diseases like Parkinsons, and drugs that work to inhibit ferroptosis have shown an ability to halt neurodegeneration in animal models of the disease.

Apoptosis refers to a programmed cell death mechanism, as opposed to cell death caused by injury. Both apoptosis and ferroptosis speed the death of dopaminergic neurons.

CRISPR/Cas9 may help to pinpoint the key players in cell death that promote the loss of dopaminergic neurons in Parkinsons disease, while understanding the array of proteins that are involved in these processes.

These insights into the mechanisms of PD pathology [disease mechanisms] may be used for the identification of new targets for therapeutic interventions and innovative approaches to genome editing, including CRISPR/Cas9, the researchers wrote.

Genome editing technology is currently being used in clinical trials to treat patients with late-stage cancers and inherited blood disorders, Artyukhova notes in the release.

These studies allow us to see vast potential of genome editing as a therapeutic strategy. Its hard not to be thrilled and excited when you understand that progress of genome editing technologies can completely change our understanding of treatment of Parkinsons disease and other neurodegenerative disorders, she adds.

Patricia holds a Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She has also served as a PhD student research assistant at the Department of Microbiology & Immunology, Columbia University, New York.

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CRISPR/Cas9 Potential in Advancing Parkinson's Understanding and Treatment Focus of Review Study - Parkinson's News Today

Alzheimers Disease May Be Caused by Copper In The Brain – Science Times

Lysette Maurice N. SandovalSep 18, 2019 09:40 AM EDT

Tai-Yen Chen, a chemist from the University of Houston, is conducting a study to explore the link between a person's exposure to molecules of copper protein in the brain cells and the risks of suffering from a neurodegenerative disease like Alzheimer's.

"For 100 years, scientists have continued to search for answers to Alzheimer's disease and the many potential causes, but none of them have been proven successful. Up until today, no one really knows why some people suffer from Alzheimer's and others do not," Chen said. He was recently awarded by the National Institute of General Medical Science funding amounting to $1.9 million dollars to further develop his theory that the copper protein balance in every cell in the brain may be the culprit to people developing and suffering from Alzheimer's disease.

Copper is considered an essential nutrient in the growth of cells in the human brain. They help the neurons receive and deliver messages all throughout the body. Every healthy cells have a certain amount of copper that is strictly regulated to remain at a certain level. Scientists from long ago have already uncovered the fact that patients with Alzheimer's disease have an unusually high level of copper on brain cells, which basically became the signature of the degenerative disease.

"The findings were unusual and we wanted to learn more about it," Chen said. His study will be looking into the biological regulation of copper levels in brain cells to help doctors identify potential cases of Alzheimer's disease. The abnormal growth of copper in the cells will be a clear indicator that will establish the link between the two. There are several other degenerative diseases that are linked to the imbalance of copper in the human brain. Menkes disease, a nervous system disorder that is characterized by low levels of copper, while Wilson disease is a genetic disorder that is caused by having too much copper present in the head.

"We want to know how the cells are able to regulate the copper levels inside them to be able to achieve the optimum amount of copper level," said Chen. He will be working mostly cells from the brain and the liver. "The study will be employing a unique method of looking into individual cells to be able to identify its behavior. The process will be repeated in all the other cells that will become part of the study to get the information needed. The collective behavior of these cells will help us uncover the facts we need to better understand the relationship between copper content in cells."

When the study is able to figure out how the regulation of copper content in cells is done naturally, particularly between normal, healthy cells and diseased ones, the findings will truly shed light on the overall pathology of Alzheimer's disease.

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Alzheimers Disease May Be Caused by Copper In The Brain - Science Times

Toyobo to market RNA Analysis Kit based on RIKEN technology to help develop genomic medicine – BioSpace

OSAKA, Japan, Sept. 18, 2019 /PRNewswire/ -- Toyobo Co., Ltd. has productized a ribonucleic acid (RNA) analysis kit based on a novel system titled RamDA-seq*1,that allows full-length sequencing of the total RNA of a single cell. The Laboratory for Bioinformatics Research at the RIKEN Center for Biosystems Dynamics Research developed this method last year.

As national health insurance programs in Japan have covered genomic medicine since June 2019, medical care is progressing to be tailored to individual patients by selecting suitable treatment and drugs after analyzing a patient's genes. In recent years, genetic information in a single cell has proven to be effective in treating diseases such as cancer caused by gene mutations, because each cell has different genetic properties. However, conventional methods have been unable to reliably detect disease-causing mutations from an extremely small amount of RNA*2 derived from a single cell.

RIKEN, which is based in Wako City, Saitama Prefecture, is one of Japan's largest scientific research institutes. RIKEN has developed a novel method, RamDA-seq, which enables the amplification of RNA in low bias and the detection of an expression level of genes in a single cell. This method allows the comprehensive identification of RNA varieties and their amounts in a single cell. It drastically improved the analytical precision of a disease-causing gene expression level and mutations in various RNAs, including non-polyadenylated RNAs whose functions remain unclear due to the difficulty in their detection.

RNA Analysis Kit, which Toyobo productized under RIKEN's technological guidance, consists of reagents and a user manual necessary to conduct RamDA-seq. The kit makes it possible to prepare samples more smoothly and stably, as described in articles published by RIKEN.

The kit is expected to expand the use of RamDA-seq, to accelerate the development of various medical fields ranging from basic research to regenerative and genomic medicine. Toyobo will launch the product for research institutes including pharmaceutical companies developing drugs for cancer and other diseases on September 30, 2019. The company aims to achieve annual sales of JPY 1 billion in fiscal 2022.

RNA Analysis Kit to be marketed

Genome includes a complete set of genetic information of the cell, which is recorded as sequences of four types of nucleotide in a biological polymer called DNA. Genes are regions that record genetic information in genome. Genetic information is read out by synthesizing RNA using DNA as a template.The cells that constitute our bodies control its gene expression to perform various functions, while having almost the same genetic information. Since this gene expression is mediated by molecules called RNA, a comprehensive analysis of RNA is effective in understanding the individual characters of individual cells.

About Toyobo Co., Ltd.: Toyobo Co., Ltd (Toyobo) is a worldwide specialty chemical company, headquartered in Osaka, Japan. Since its foundation in 1882 as a textile company, Toyobo has expanded the boundaries of its business beyond textiles to specialty business segments such as industrial and packaging films, functional polymers, industrial materials and healthcare with its unique core technologies originated in textiles and chemical fibers.

For more information, contact: https://www.toyobo-global.com/

View original content:http://www.prnewswire.com/news-releases/toyobo-to-market-rna-analysis-kit-based-on-riken-technology-to-help-develop-genomic-medicine-300920735.html

SOURCE Toyobo Co., Ltd.

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Toyobo to market RNA Analysis Kit based on RIKEN technology to help develop genomic medicine - BioSpace

Cancer Cells Devise Way To Survive Chemotherapy – Medical Daily

Cannibalism among cancer cells is one of the major causes of chemotherapy resistance.

Resistance, which occurs when cancers that have been responding to chemo suddenly begin to grow, is normally associated with the massive production by cancer cells of p-glycoprotein pumps, gene amplification and the repair of DNA breaks caused by some anti-cancer drugs such as doxorubicin, among others.

But cannibalism does exist and while uncommon, adds to the burden of curing or mitigating cancer via chemotherapy.

A new study from Tulane University suggests some cancer cells survive chemotherapy by devouring their neighboring tumor cells in a ruthless bid to withstand chemotherapy. This cellular cannibalism is thought to give predatory cancer cells the energy they need to stay alive. It also allows them to begin tumor relapse after the chemotherapy treatment is completed.

Chemotherapy drugs, among them doxorubicin, kill cancer cells by damaging their DNA. Unfortunately, cancer cells that survive the initial treatment give rise to relapsed tumors.

This is an especially thorny problem in breast cancers that retain a normal copy of a gene called TP53. This protein acts as a tumor suppressor. This means it regulates cell division by keeping cells from growing and proliferating too fast or in an uncontrolled way.

Some cancer cells generally stop proliferating and enter a dormant but metabolically active state known as senescence, instead of dying due to chemotherapy-induced DNA damage. Senescent cancer cells also produce large amounts of inflammatory molecules and other factors that can promote the tumors regrowth.

Chemotherapy-treated breast cancer patients with normal TP53 genes become prone to relapse and have poor survival rates.

Understanding the properties of these senescent cancer cells that allow their survival after chemotherapy treatment is extremely important, Crystal A. Tonnessen-Murray, a postdoctoral research fellow at James G. Jacksons laboratory at the Tulane University School of Medicine, who led the research team, said.

Her team also discovered that senescent breast cancer cells frequently engulf neighboring cancer cells following exposure to doxorubicin or other chemotherapy drugs. Researchers observed this surprising behavior in cancer cells grown in the lab and also in tumors growing in mice.

They also found that lung and bone cancer cells are also capable of engulfing their neighbors after becoming senescent.

Tonnessen-Murray and her colleagues found that senescent cancer cells activate a group of genes, which are normally active in white blood cells, that engulf invading microbes or cellular debris. They saw that after eating their neighboring cancer cells, senescent cancer cells digested them by delivering them to lysosomes, which are acidic cellular structures highly active in senescent cells.

But the most important finding was that this process helps senescent cancer cells stay alive. Senescent cancer cells that engulfed neighboring cells survived in culture for longer than senescent cancer cells that didnt.

The blood test could rapidly confirm whether breast cancer is responding to the drug palbociclib. Miguel . Padrin/Pexels

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Cancer Cells Devise Way To Survive Chemotherapy - Medical Daily

Plant used in traditional Chinese medicine is effective against malignant skin cancer – Innovation Origins

Malignant skin cancer is one of the most dangerous types of cancer. 5000 people are diagnosed with it every year in Austria. The number of cases has risen sharply in recent decades. Thirty years ago, there were only five hundred people suffering from malignant melanomas.

In contrast, mortality rates have risen by only a slight margin. If detected early, the chances for recovery are good. But as soon as metastases start to form, the chances for a cure drop rapidly. This is also due to the fact that there are hardly any long-term effective treatment options (source: Austrian Society for Dermatology (GDV).

The Institute for Pharmaceutical Sciences at the University of Graz has been conducting research for many years into natural substances that can be used for the treatment of cancer. The team has now achieved a breakthrough which might also make it possible to cure advanced stages of malignant skin cancer. An active substance from the roots of theOnosma paniculata plant, a subspecies of the borage plant (also known as forget-me-not), has been successfully tested on cancer cells and on mice. The researchers also succeeded in modifying the active ingredient and further improving its effect.

The project was carried out in collaboration with the Technical University of Munich and the Helmholtz Institute Munich (the German Research Center for Environmental Health). The group was led by Rudolf Bauer from the Institute of Pharmaceutical Sciences (Pharmacognosy) at the University of Graz. He has been researching medicinal plants that are used in traditional medicine for fifteen years with the aim of identifying bioactive ingredients and discovering new key substances.

The main purpose of the research was to identify the plants that are used in traditional Chinese medicine (TCM) as cures for cancer-related diseases. Cancer-related, because the definition of cancer in TCM differs from that in Western medicine, Nadine Kretschmer explains. She has worked with the project and is a biologist at the Heidelberg University of Medicine. Another goal was to test their suitability as an active substance for a particular medicine. Approximately eighty percent of all Chemotherapeutic drugs are derived from nature, especially from plants. This figure is as high as seventy percent just for cancer therapies. The active substances on the market are usually synthetically modified even more so that they have an optimal effect. The active substances are then usually produced synthetically or biotechnologically for commercial purposes, Kretschmer says.

The contribution made by the University of Graz to the project was based on a database of several hundred medicinal plants used in traditional medicine which have been accumulated over several years. This project focused on plants from traditional Chinese medicine (TCM). Part of the contribution made by the German partners was the implementation of RNA (ribonucleic acid) sequencing and preliminary evaluations. RNA sequencing serves as a means of determining the nucleotide sequence in the RNA and provides information on how the genetic information of a gene is expressed.

The project included seventy-six of the most promising specimens from the database. These were dried, processed into 253 extracts and tested on various cancer cells. In the end, it was the Onosma Paniculata Bureau & Franch, a type of borage shrub, that offered prospects for further studies. The potent substance --Dimethylacrylshikonin (DMAS) is found in the root of the plant.

During the experiments, the substance was tested on cells of malignant melanomas. The substance destroyed the cells thereby confirming their efficacy. In order to test the substance for side effects, the initial in vivo tests were carried out on mice that were afflicted with skin cancer. - dimethylacrylshikonin was injected directly into the tumor which caused it to change and die off. Two types of cell death were observed:

There were no side effects.

Subsequent trials were conducted expressly with the aim of modifying the substance in order to improve its efficacy. A specific shikonin derivative proved to be especially effective. This demonstrated that the substance is well suited for the development of pharmaceuticals. In the meantime, two more follow-up projects have been planned. More extensive studies are required and the method of application is still an open question, Kretschmer states.

Kretschmer emphasizes that TCM was purely an inspiration for the active substance. It is still not clear how this works within TCM. Normally no singular plants are used in TCM, instead plant mixtures are used. These are prepared like tea. In an attempt to unravel the effect of TCM, the team cooked up the dried plant according to the TCM method and used it in cell cultivation experiments. However, no anti-tumor effect was observed. Kretschmer sees more potential in an oil-based preparation method that is applied to the affected areas of the skin. This is because shikonins are found in higher concentrations in the oil.

Over the course of the project, the identity of the borage plant species sold as TCM remedies was also tested. There are roots that look very similar to the plant we are studying and we have found that the species is often sold under fake names in China. This is problematic because some of the plants that are marketed contain substances that are potentially harmful.

Kretschmer and the research team found a technical solution to the problem: a method which uses thin-layer chromatography for the identification of plants. This innovation is based on a CAMAG system and is simple enough for use in pharmacies.

Thin-layer chromatography (TLC) is a physicochemical separation process that is used to examine the composition of specimens.

The core project was funded by the Austrian Science Fund FWF and was completed in early 2019.

Publications:

Kretschmer, N.; Deutsch, A.; Durchschein, C.; Rinner, B.; Stallinger, A.; Higareda-Almaraz, J.C.; Scheideler, M.; Lohberger, B.; Bauer, R.: Comparative Gene Expression Analysis in WM164 Melanoma Cells Revealed That --Dimethylacrylshikonin Leads to ROS Generation, Loss of Mitochondrial Membrane Potential, and Autophagy Induction, in: Molecules 2018, 23

Durchschein, C.; Hufner, A.; Rinner, B.; Stallinger, A.; Deutsch, A.; Lohberger, B.; Bauer, R.; Kretschmer, N.: Synthesis of Novel Shikonin Derivatives and Pharmacological Effects of Cyclopropylacetylshikonin on Melanoma Cells, in: Molecules 2018, 23

Jahanafrooz, Z; Stallinger, A; Anders, I; Kleinegger, F; Lohberger, B; Durchschein, C; Bauer, R; Deutsch, A; Rinner, B; Kretschmer, N.: Influence of silibinin and --dimethylacrylshikonin on chordoma cells, in: Phytomedicine 2018, 49

Also of interest:

Dual Therapy to Reduce the Relapse Rate in Cancers

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Plant used in traditional Chinese medicine is effective against malignant skin cancer - Innovation Origins

The end of aging: Are you ready to live to 150? – Mashable

Once weve conquered our diets, instituted a regimen of exercise and saunas and cold plunges, doused ourselves in NMN and resveratrol and Metformin and benign viruses, quit smoking and cut down our drinking and remembered to wear our seatbelts, theres one main obstacle remaining in the way of an extra-long and healthy life: our guilt.

Whether its hard-wired or a result of societal expectations, we tend to feel that old farts should not outstay their welcome. Leave some room for future generations, we grumble under our breath, out of earshot of elderly relatives. Youre already taking up too much of the housing stock, making it near-impossible for millennials to buy homes. You want to bankrupt Social Security and Medicare too?

Just last month, Ezekiel Emanuel, the chair of the University of Pennsylvanias department of medical ethics (and a chief architect of Obamacare) confirmed that he stood by his controversial 2014 essay: Why I hope to die at 75. Despite the onslaught of anti-aging research, Emmannuel (now 62) said his main arguments still held water: That people in their 80s who were still vigorous were not doing meaningful work; that authors above 75 were not producing brand-new books but simply re-ploughing old furrows.

Let's leave aside the fact that's a pretty weird metric to judge the worth of a life -- sorry, grandma, time to go, you're not doing meaningful work or writing new books! Emanuel's argument ignores what biologists like Sinclair are telling us. The more we age in good health, the more useful we will be.

Sinclair, as you might expect, could not disagree with Emanuel more. First of all, he says, lets assume everyone stopped dying of age-related causes tomorrow and they wont, even under the most extreme anti-aging regimen. But if they do, thats only 100,000 extra people per day sticking around. (Around 150,000 people die every day, roughly two-thirds of them from age-related causes.)

Compare that to the worlds current growth rate. More than 350,000 babies arrive every 24 hours. Earth's population is growing because of the size of the average family in the developing world, not because more people are living longer. The main way to bring it down is to educate more women and move more families into cities where, by the way, we shouldnt blame Baby Boomers for the lack of housing. We simply need to build more.

Total human population should level off at around 11 billion around the time your century dawns, whether or not the aged continue to die. And as for the threat of climate change well, perhaps the older generation will start to pay more attention when theyre actually going to live with the effects themselves. Or when they have to look their great-great-grandchildren in the eyes and explain their inaction.

Secondly, a healthy longevity boom would actually take an enormous burden off the healthcare system. Reducing just one of the major killers like heart disease, even by 10 percent, could savetrillions of dollars, money that can then be reinvested in medical research or just returned to patients in the form of lower costs. And thats the whole point of treating aging as the ultimate disease, the one that effectively produces all the others. (For example, Sinclair writes, smoking makes lung cancer five times more likely, but just living from 20 to 70 increases your chances of getting the disease a thousandfold, even if youve never sucked on a cancer stick.)

Aging is by far the biggest risk factor in any disease, by an order of magnitude, Sinclair says; having volunteered in nursing homes with his wife, he knows whereof he speaks. Dont delude yourself: Getting old and getting sick is not fun, for you or for your family. So I believe we have an obligation to preserve our health for as long as possible.

Excerpt from:
The end of aging: Are you ready to live to 150? - Mashable