Psoriasis: New Treatments Help Millions Manage Common Skin Condition – Newsmax

For years, psoriasis suffers have battled patches of rough, reddened, and intensely itchy skin that can cause pain as well embarrassment, with little hope of relief.

But major breakthroughs have been logged in the treatment of this potentially debilitating disorder that affects almost 10 million Americans, including small children. And if you are suffering from the disease, its time to take action.

To spotlight the treatments that have emerged in recent years, the National Psoriasis Foundation is observing National Psoriasis Action month in August.

The NPF Foundation wants to spread the word that there have been tremendous advancements in the number of treatment options for people living with the condition. The NPF has even launched a website to educate patients, caregivers and health care professionals about the resources to treat psoriatic disease.

Throughout August, people impacted by psoriasis can participate in interactive quizzes that will help them better understand and manage their disease, Dr. Michael Siegel, Ph.D, vice president of Research Programs at the NPF tells Newsmax Health.

Psoriasis often develops between the ages of 15 and 35, but it can develop at any age. While scientists do not know exactly what causes psoriasis, it is known that the immune system and genetics play major roles in its development.

Usually, something triggers the condition to flare. The skin cells in people with psoriasis grow at an abnormally fast rate, which leads to painful lesions on the body.

The genetic link is clear, says Siegal.

If one parent has psoriasis, there is about a 10 percent chance of a child contracting it. If both parents have psoriasis, the chance increases to 50 percent, he notes.

Dr. Kenneth Beer, associate clinical professor of dermatology at the University of Miami, tells Newsmax Health that the No. 1 myth about psoriasis is that it is just dry skin.

Its far more than that, he says. Psoriasis is an immune disease in which the body stimulates growth of skin cells in an abnormal way. It is largely genetic and may be associated with stress, infection medication or a range of other issues. In addition to affecting the skin, it can frequently affect the joints of the body.

Another myth is that the condition is contagious. Not so, says Beer. And while it is not curable at this point in time, it is manageable and treatable. But if you dont take care of your psoriasis, it can lead to serious medical conditions.

According to the Mayo Clinic, people with psoriasis are at a great risk for Type 2 diabetes as well as vision problems and heart disease. About 30 percent of people who have psoriasis will develop psoriatic arthritis, according to the NPF.

Reality TV star Kim Kardashian revealed that she suffers from the condition and that stress plays a key role in her flare-ups of psoriasis. Two-time Grammy winning songstress LeAnn Rimes kept her struggle hidden until 2008 when she decided to open up about her experience as part of the Stop Hiding, Start Living awareness campaign sponsored by Abbott, which makes the psoriasis drug, Humira.

Other celebs with psoriasis include comedian Jon Lovitz and Leave it to Beaver star Jerry Mathers, who admits that the condition is no laughing matter.

Siegel says that treating psoriasis involves good disease management and paying attention overall health.

With advances in the number of treatment options available today for people living with psoriasis its easier than ever to treat the condition, he says. The biggest breakthrough came 10 years ago with the introduction of injectable biologics which changed the lives of patients and their providers.

By targeting specific pathways in the immune system, these biologics have demonstrated remarkable outcomes in clinical trials. Moving forward, scientists are likely to reveal even more effective treatments and will be able to harness the same targeted therapy for oral and topical treatments as well.

Some examples of biologic drugs to treat psoriasis include Humira, Enbrel, and Remicade.

Siegel says that some people believe that eliminating certain foods from their diet, such as gluten, dairy, sugar, or red meat can reduce inflammation and therefore lower their chances of a psoriatic flare.

Others believe that consuming certain vitamins, herbs and supplements, such as fish oil or turmeric, can do the same, he says. The truth is that there is not enough scientific evidence to substantiate these claims, and the medical community doesnt know for sure how diet impacts psoriatic disease.

What the medical community does agree on, however, is that people with psoriatic disease should maintain a healthy weight, and thats where diet and exercise can play and important role. Research has found that maintaining a healthy weight lowers the risk of developing co-morbidities or related health conditions like diabetes or cardiovascular disease.

Siegel says that another big myth about psoriasis is that there isnt a treatment available for patients to achieve clear or nearly clear skin.

This is simply not true, he says. There have been tremendous advancements and there are currently a number of safe, effective and affordable options. The first step people living with psoriasis should take is to work with their health care provider to discuss a treatment strategy. By following a goal-oriented, trackable treatment strategy, people living with psoriasis should expect to begin seeing results in three to six months.

Adds Beer: Psoriasis is now one of the most researched skin diseases and each year we get better and better treatments. See your dermatologist to get more information.

2017 NewsmaxHealth. All rights reserved.

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Psoriasis: New Treatments Help Millions Manage Common Skin Condition – Newsmax

Mouse model of human immune system inadequate for stem cell studies – Medical Xpress

August 22, 2017 Credit: Martha Sexton/public domain

A type of mouse widely used to assess how the human immune system responds to transplanted stem cells does not reflect what is likely to occur in patients, according to a study by researchers at the Stanford University School of Medicine. The researchers urge further optimization of this animal model before making decisions about whether and when to begin wide-scale stem cell transplants in humans.

Known as “humanized” mice, the animals have been engineered to have a human, rather than a murine, immune system. Researchers have relied upon the animals for decades to study, among other things, the immune response to the transplantation of pancreatic islet cells for diabetes and skin grafts for burn victims.

However, the Stanford researchers found that, unlike what would occur in a human patient, the humanized mice are unable to robustly reject the transplantation of genetically mismatched human stem cells. As a result, they can’t be used to study the immunosuppressive drugs that patients will likely require after transplant. The researchers conclude that the humanized mouse model is not suitable for studying the human immune response to transplanted stem cells or cells derived from them.

“In an ideal situation, these humanized mice would reject foreign stem cells just as a human patient would,” said Joseph Wu, MD, PhD, director of Stanford’s Cardiovascular Institute and professor of cardiovascular medicine and of radiology. “We could then test a variety of immunosuppressive drugs to learn which might work best in patients, or to screen for new drugs that could inhibit this rejection. We can’t do that with these animals.”

Wu shares senior authorship of the research, which will be published Aug. 22 in Cell Reports, with Dale Greiner, PhD, professor in the Program in Molecular Medicine at the University of Massachusetts Medical School, and Leonard Shultz, PhD, professor at the Jackson Laboratory. Former postdoctoral scholars Nigel Kooreman, MD, and Patricia de Almeida, PhD, and graduate student Jonathan Stack, DVM, share lead authorship of the study.

“Although these mice are fully functional in their immune response to HIV infection or after transplantation of other tissues, they are unable to completely reject the stem cells,” said Kooreman. “Understanding why this is, and whether we can overcome this deficiency, is a critical step in advancing stem cell therapies in humans.”

“Humanized mice are critical preclinical models in many biomedical fields helping to bring basic science into the clinic, but as this work shows, it is critical to frame the question properly,” said Greiner. “Multiple laboratories remain committed to advancing our understanding and enhancing the function of engrafted human immune systems.”

Greiner and Shultz helped to pioneer the use of humanized mice in the 1990s to model human diseases and they provided the mice used in the study.

Understanding stem cell transplants

The researchers were studying pluripotent stem cells, which can become any tissue in the body. They tested the animals’ immune response to human embryonic stem cells, which are naturally pluripotent, and to induced pluripotent stem cells. Although iPS cells can be made from a patient’s own tissues, future clinical applications will likely rely on pre-screened, FDA-approved banks of stem cell-derived products developed for specific clinical situations, such as heart muscle cells to repair tissue damaged by a heart attack, or endothelial cells to stimulate new blood vessel growth. Unlike patient-specific iPS cells, these cells would be reliable and immediately available for clinical use. But because they won’t genetically match each patient, it’s likely that they would be rejected without giving the recipients immunosuppressive drugs.

Humanized mice were first developed in the 1980s. Researchers genetically engineered the mice to be unable to develop their own immune system. They then used human immune and bone marrow precursor cells to reconstitute the animals’ immune system. Over the years subsequent studies have shown that the human immune cells survive better when fragments of the human thymus and liver are also implanted into the animals.

Kooreman and his colleagues found that two varieties of humanized mice were unable to completely reject unrelated human embryonic stem cells or iPS cells, despite the fact that some human immune cells homed to and were active in the transplanted stem cell grafts. In some cases, the cells not only thrived, but grew rapidly to form cancers called teratomas. In contrast, mice with unaltered immune systems quickly dispatched both forms of human pluripotent stem cells.

The researchers obtained similar results when they transplanted endothelial cells derived from the pluripotent stem cells.

A new mouse model

To understand more about what was happening, Kooreman and his colleagues created a new mouse model similar to the humanized mice. Instead of reconstituting the animals’ nonexistent immune systems with human cells, however, they used immune and bone marrow cells from a different strain of mice. They then performed the same set of experiments again.

Unlike the humanized mice, these new mice robustly rejected human pluripotent stem cells as well as mouse stem cells from a genetically mismatched strain of mice. In other words, their newly acquired immune systems appeared to be in much better working order.

Although more research needs to be done to identify the cause of the discrepancy between the two types of animals, the researchers speculate it may have something to do with the complexity of the immune system and the need to further optimize the humanized mouse model to perhaps include other types of cells or signaling molecules. In the meantime, they are warning other researchers of potential pitfalls in using this model to screen for immunosuppressive drugs that could be effective after human stem cell transplants.

“Many in the fields of pluripotent stem cell research and regenerative medicine are pushing the use of the humanized mice to study the human immune response,” said Kooreman. “But if we start to make claims using this model, assuming that these cells won’t be rejected by patients, it could be worrisome. Our work clearly shows that, although there is some human immune cell activity, these animals don’t fully reconstitute the human immune system.”

The researchers are hopeful that recent advances may overcome some of the current model’s limitations.

“The immune system is highly complex and there still remains much we need to learn,” said Shultz. “Each roadblock we identify will only serve as a landmark as we navigate the future. Already, we’ve seen recent improvements in humanized mouse models that foster enhancement of human immune function.”

Explore further: Study provides hope for some human stem cell therapies

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Mouse model of human immune system inadequate for stem cell studies – Medical Xpress

Immunotherapy, Nanotech Combine to Kill Cancer Cells More … – Genetic Engineering & Biotechnology News

Scientists at Duke University say they have combined a cancer immunotherapeutic with nanotechnology to improve the efficacy of both therapies in a mouse study. They published their work, “Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) for the Treatment of Unresectable and Metastatic Cancers,” in Scientific Reports.

The new approach also attacked satellite tumors and distant cancerous cells, leading to two mice being cured of the disease and one being vaccinated against it.

Using a combination of immune-checkpoint inhibition and plasmonic gold nanostar (GNS)-mediated photothermal therapy, we were able to achieve complete eradication of primary treated tumors and distant untreated tumors in some mice implanted with the MB49 bladder cancer cells, wrote the investigators. Delayed rechallenge with MB49 cancer cells injection in mice that appeared cured by SYMPHONY did not lead to new tumor formation after 60 days observation, indicating that SYMPHONY treatment induced effective long-lasting immunity against MB49 cancer cells.

“The ideal cancer treatment is noninvasive, safe, and uses multiple approaches,” said Tuan Vo-Dinh, Ph.D., the R. Eugene and Susie E. Goodson Professor of Biomedical Engineering, professor of chemistry, and director of the Fitzpatrick Institute for Photonics at Duke University. “We also aim at activating the patient’s own immune system to eradicate residual metastatic tumors. If we can create a long-term anticancer immunity, then we’d truly have a cure.”

The specific photothermal immunotherapy was developed by Duke researchers and uses lasers and gold nanostars to heat and kill tumors in combination with an immunotherapeutic drug. The technique works based on the ability of nanoparticles to accumulate preferentially within a tumor due to its leaky vasculature, according to the scientists, who add that gold nanostars have the advantage of geometry. With many sharp spikes, they can capture the laser’s energy more efficiently, thus permitting them to work with less exposure, making them more effective deeper within a tissue.

“The nanostar spikes work like lightning rods, concentrating the electromagnetic energy at their tips,” said Dr. Vo-Dinh. “We’ve experimented with these gold nanostars to treat tumors before, but we wanted to know if we could also treat tumors we didn’t even know were there or tumors that have spread throughout the body.”

Dr. Vo-Dinh explained that the body’s immune system protects against the growth of cancerous cells. Many tumors, however, overproduce the programmed death-ligand 1 (PD-L1) molecule, which disables T cells so they cannot attack the tumor. A number of drugs are being developed to block the action of PD-L1.

In the study, the Duke team injected bladder cancer cells into both hind legs of a group of mice. After waiting for the tumors to grow, the researchers explored a number of therapies, but only on one of the legs.

Those that received no treatments all quickly succumbed to the cancer, as did those receiving only the gold nanostar phototherapy, because the treatment did nothing to affect the tumor in the untreated leg. While a few mice responded well to the immunotherapy alone, with the drug stalling both tumors, none survived more than 49 days.

The group treated with both the anti-PD-L1 immunotherapy and the gold nanostar phototherapy fared much better, with two of the five mice surviving more than 55 days.

“When a tumor dies, it releases particles that trigger the immune system to attack the remnants,” said Dr. Vo-Dinh. “By destroying the primary tumor, we activated the immune system against the remaining cancerous cells, and the immunotherapy prevented them from hiding.”

According to Dr. Vo-Dinh, one mouse is still alive almost a year out with zero recurrence of the cancer. When more cancerous cells were injected, the mouse’s immune system attacked and destroyed them, demonstrating a vaccine effect in the cured mouse.

The Duke team has plans to follow up with larger cohorts of mice and to work with other clinical researchers to test the treatment on mouse models of brain, breast, and lung cancers.

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Immunotherapy, Nanotech Combine to Kill Cancer Cells More … – Genetic Engineering & Biotechnology News

Immunotherapy, Nanotech Combine to Kill Cancer Cells More … – Genetic Engineering & Biotechnology News

Scientists at Duke University say they have combined a cancer immunotherapeutic with nanotechnology to improve the efficacy of both therapies in a mouse study. They published their work, “Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) for the Treatment of Unresectable and Metastatic Cancers,” in Scientific Reports.

The new approach also attacked satellite tumors and distant cancerous cells, leading to two mice being cured of the disease and one being vaccinated against it.

Using a combination of immune-checkpoint inhibition and plasmonic gold nanostar (GNS)-mediated photothermal therapy, we were able to achieve complete eradication of primary treated tumors and distant untreated tumors in some mice implanted with the MB49 bladder cancer cells, wrote the investigators. Delayed rechallenge with MB49 cancer cells injection in mice that appeared cured by SYMPHONY did not lead to new tumor formation after 60 days observation, indicating that SYMPHONY treatment induced effective long-lasting immunity against MB49 cancer cells.

“The ideal cancer treatment is noninvasive, safe, and uses multiple approaches,” said Tuan Vo-Dinh, Ph.D., the R. Eugene and Susie E. Goodson Professor of Biomedical Engineering, professor of chemistry, and director of the Fitzpatrick Institute for Photonics at Duke University. “We also aim at activating the patient’s own immune system to eradicate residual metastatic tumors. If we can create a long-term anticancer immunity, then we’d truly have a cure.”

The specific photothermal immunotherapy was developed by Duke researchers and uses lasers and gold nanostars to heat and kill tumors in combination with an immunotherapeutic drug. The technique works based on the ability of nanoparticles to accumulate preferentially within a tumor due to its leaky vasculature, according to the scientists, who add that gold nanostars have the advantage of geometry. With many sharp spikes, they can capture the laser’s energy more efficiently, thus permitting them to work with less exposure, making them more effective deeper within a tissue.

“The nanostar spikes work like lightning rods, concentrating the electromagnetic energy at their tips,” said Dr. Vo-Dinh. “We’ve experimented with these gold nanostars to treat tumors before, but we wanted to know if we could also treat tumors we didn’t even know were there or tumors that have spread throughout the body.”

Dr. Vo-Dinh explained that the body’s immune system protects against the growth of cancerous cells. Many tumors, however, overproduce the programmed death-ligand 1 (PD-L1) molecule, which disables T cells so they cannot attack the tumor. A number of drugs are being developed to block the action of PD-L1.

In the study, the Duke team injected bladder cancer cells into both hind legs of a group of mice. After waiting for the tumors to grow, the researchers explored a number of therapies, but only on one of the legs.

Those that received no treatments all quickly succumbed to the cancer, as did those receiving only the gold nanostar phototherapy, because the treatment did nothing to affect the tumor in the untreated leg. While a few mice responded well to the immunotherapy alone, with the drug stalling both tumors, none survived more than 49 days.

The group treated with both the anti-PD-L1 immunotherapy and the gold nanostar phototherapy fared much better, with two of the five mice surviving more than 55 days.

“When a tumor dies, it releases particles that trigger the immune system to attack the remnants,” said Dr. Vo-Dinh. “By destroying the primary tumor, we activated the immune system against the remaining cancerous cells, and the immunotherapy prevented them from hiding.”

According to Dr. Vo-Dinh, one mouse is still alive almost a year out with zero recurrence of the cancer. When more cancerous cells were injected, the mouse’s immune system attacked and destroyed them, demonstrating a vaccine effect in the cured mouse.

The Duke team has plans to follow up with larger cohorts of mice and to work with other clinical researchers to test the treatment on mouse models of brain, breast, and lung cancers.

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Immunotherapy, Nanotech Combine to Kill Cancer Cells More … – Genetic Engineering & Biotechnology News

Genetic Variance is Key to Individual Immune Response – Genetic Engineering & Biotechnology News

Ever wonder why your friend, co-worker, or partner doesnt get as sick as you, even though they caught the same bug you did? Maybe they made some Faustian bargain that affords them greater protection to infections, or perhaps they are part of some top-secret government experiment that injects them with an array of antigens isolated from an alien race living in Area 51. While both theories are potential explanations, it seems likely that differences in response to infection lie in something a bit more scientificlike genetics. Now, a collaborative team of investigators from the University of Bonn, Germany, and the New York Genome Center has just published findings that map several genetic variants that affect how much gene expression changes in response to an immune stimulus.

Results from the new studypublished in Nature Communications in an article entitled Genetic Regulatory Effects Modified by Immune Activation Contribute to Autoimmune Disease Associationsoffer novel insights into the genetic contribution to varying immune responses among individuals and its consequences on immune-mediated diseases.

Our defense mechanisms against microbial pathogens rely on white blood cells that are specialized to detect infection,” explained co-senior study investigator Veit Hornung, Ph.D., chair of immunobiochemistry at the Ludwig-Maxmilians-Universitt in Munich. Upon encounter of microbes, these cells trigger cellular defense programs via activating and repressing the expression of hundreds of genes.

We wanted to understand how genetic differences between individuals affect this cellular response to infection,” added co-senior study investigator Johannes Schumacher, Ph.D., a research scientist at the Institute of Human Genetics within the University of Bonn.

The human immune system plays a central role in autoimmune and inflammatory diseases, cancer, metabolism, and aging. The researchers discovered hundreds of genes where the response to immune stimulus depended on the genetic variants carried by the individual.

“These genes include many of the well-known genes of the human immune system, demonstrating that genetic variation has an important role in how the human immune system works,” noted lead study investigator Sarah Kim-Hellmuth, Ph.D., a postdoctoral researcher at the New York Genome Center. “While earlier studies have mapped some of these effects, this study is particularly comprehensive, with three stimuli and two-time points analyzed.”

In the current study, the research team captured genetic variants whose effects on gene regulation were different depending on the different infectious state of the cells. These included four associations to diseases such as cholesterol level and celiac disease. Moreover, the researchers discovered a trend of genetic risk for autoimmune diseases such as lupus and celiac disease to be enriched for gene regulatory effects modified by the immune state.

“Here, we isolate monocytes from 134 genotyped individuals, stimulate these cells with three defined microbe-associated molecular patterns (LPS, MDP, and 5-ppp-dsRNA) [lipopolysaccharide, muramyl dipeptide, and 5′ triphosphate double-stranded RNA], and profile the transcriptomes at three-time points, the authors wrote. Mapping expression quantitative trait loci (eQTL), we identify 417 response eQTLs (reQTLs) with varying effects between conditions. We characterize the dynamics of genetic regulation on early and late immune response and observe an enrichment of reQTLs in distal cis-regulatory elements. In addition, reQTLs are enriched for recent positive selection with an evolutionary trend towards enhanced immune response. Finally, we uncover reQTL effects in multiple GWAS [genome-wide association study] loci and showed a stronger enrichment for response than constant eQTLs in GWAS signals of several autoimmune diseases.

Co-senior author Tuuli Lappalainen, Ph.D., assistant professor at Columbia University and core member of the New York Genome Center added that this data supports a paradigm where genetic disease risk is sometimes driven not by genetic variants causing constant cellular dysregulation, but by causing a failure to respond properly to environmental conditions such as infection.”

Using the collected monocyte samples, the researchers treated the cells with three components that mimic infection with bacteria or a virus. They then analyzed how cells from different individuals respond to infection by measuring gene expression both during the early and late immune response. Integrating the gene expression profiles with genome-wide genetic data of each individual, they were able to map how genetic variants affect gene expression, and how this genetic effect changes with the immune stimulus.

Findings from this new study provide a highly robust and comprehensive dataset of innate immune responses and show wide variation among individuals exposed to diverse pathogens over multiple time points. The investigators identified population differences in immune response and demonstrated that immune response modifies genetic associations to disease. The research sheds light on the genomic elements underlying response to environmental stimuli and the dynamics and evolution of immune response.

“It’s been known for a long time that most diseases have both genetic and environmental risk factors, concluded Dr. Lappalainen. But it’s actually more complicated than that because genes and environment interact. As demonstrated in our study, a genetic risk factor may manifest only in certain environments. We are still in early stages of understanding the interplay of genetics and environment, but our results indicate that this is a key component of human biology and disease. The molecular approach that we took in our study can be a particularly powerful way for researchers to delve deeper into this question.”

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Genetic Variance is Key to Individual Immune Response – Genetic Engineering & Biotechnology News

Expert dispels myths about psoriasis – Gulf Times

The Hamad Medical Corporation (HMC) has launched a campaign as part of Psoriasis Awareness Month this month. It is estimated that 3% of Qatars population is affected by the disease. Men and women develop psoriasis at equal rates. The condition is often diagnosed between the ages of 15 and 35, but it can develop at any age. The main goal of Psoriasis Awareness Month is to raise awareness, encourage research and advocate for better care for individuals who have the disease. The month is also an opportunity to educate the public about the disease and to dispel common myths. Psoriasis is a chronic, genetic autoimmune disease that causes red, scaly patches on the skin. It causes cells to rapidly build up on the surface of the skin. It typically occurs on the knees, elbows, and scalp but can affect the torso, palms and soles of the feet or any other part of the skin. According to Dr Ahmad Hazem Takiddin, dermatology and venereology consultant at HMC, there are a number of common misconceptions about psoriasis, ranging from the condition being contagious to occurring due to poor hygiene. Psoriasis is an autoimmune disease which affects the skin. The patches can crack and bleed and this causes some people to think the condition is contagious. This is not true. Genetics and the immune system of a person play a vital role in the development of the disease. In those with psoriasis, the immune system sends abnormal signals that significantly accelerate the growth process of skin cells, Takiddin said. He emphasised that psoriasis is not caused or worsened by poor personal hygiene. People with the disease have a genetic tendency to develop it. There are certain things that can trigger flare-ups, including skin injury, stress, hormonal changes, infections and some medications. Most people with the disease experience cycles of clear skin and outbreaks, he said.

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Expert dispels myths about psoriasis – Gulf Times

Stem-cell treatment may harm heart disease patients – ISRAEL21c

For patients with severe and end-stage heart failure there are few treatment options left apart from transplants and stem-cell therapy. But a new Israeli study finds that stem-cell therapy may harm heart-disease patients.

The research, led by Prof. Jonathan Leor of Tel Aviv Universitys Sackler Faculty of Medicineand Sheba Medical Center and conducted by TAUs Dr. Nili Naftali-Shani, explores the current practice of using cells from the host patient to repair tissue and contends that this can prove toxic for patients.

We found that, contrary to popular belief, tissue stem cells derived from sick hearts do not contribute to heart healing after injury, said Leor. Furthermore, we found that these cells are affected by the inflammatory environment and develop inflammatory properties. The affected stem cells may even exacerbate damage to the already diseased heart muscle.

Tissue or adult stem cells blank cells that can act as a repair kit for the body by replacing damaged tissue encourage the regeneration of blood vessel cells and new heart muscle tissue. Faced with a worse survival rate than many cancers, many heart-failure patients have turned to stem-cell therapy as a last resort.

But our findings suggest that stem cells, like any drug, can have adverse effects, said Leor. We concluded that stem cells used in cardiac therapy should be drawn from healthy donors or be better genetically engineered for the patient.

The researchers, who published their study in the journal Circulation, also discovered the molecular pathway involved in the negative interaction between stem cells and the immune system as they isolated stem cells in mouse models of heart disease. Afterward, they focused on cardiac stem cells in patients with heart disease.

The results could help improve the use of autologous stem cells those drawn from the patients themselves in cardiac therapy, Leor said.

We showed that the deletion of the gene responsible for this pathway can restore the original therapeutic function of the cells, said Leor. Our findings determine the potential negative effects of inflammation on stem-cell function as theyre currently used. The use of autologous stem cells from patients with heart disease should be modified. Only stem cells from healthy donors or genetically engineered cells should be used in treating cardiac conditions.

The researchers are currently testing a gene editing technique (CRISPER) to inhibit the gene responsible for the negative inflammatory properties of the cardiac stem cells of heart disease patients. We hope our engineered stem cells will be resistant to the negative effects of the immune system, said Leor.

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Stem-cell treatment may harm heart disease patients – ISRAEL21c

Rare leukemia targeted by modifying patients’ immune cells – New Haven Register

Photo: Arnold Gold / Hearst Connecticut Media

Dr. Steven Gore at the Advanced Cell Therapy Lab at Smilow Cancer Hospital in New Haven, where cells are manufactured that fight a rare form of leukemia.

Dr. Steven Gore at the Advanced Cell Therapy Lab at Smilow Cancer Hospital in New Haven, where cells are manufactured that fight a rare form of leukemia.

Rare leukemia targeted by modifying patients immune cells

NEW HAVEN >> Young patients with a particular type of leukemia who have relapsed after going into remission may find new hope through a treatment that involves modifying a patients own T cells, an important part of the immune system, to destroy cancer cells.

While the therapy, in which genes are inserted into a patients T cells, is expected to receive Food and Drug Administration approval soon for pediatric patients, researchers hope that it will be effective for adult patients as well and for more types of cancers, according to Dr. Steven Gore, director of hematologic malignancies at the Yale Cancer Center.

The cancer thats the focus of this T cell therapy is B-lineage acute lymphoblastic leukemia, which is the most common leukemia in kids and its commonly cured in the 2- to 10-year-old age group, Gore said. He said about 70 percent of children with the cancer are cured.

However, the rest suffer a recurrence of the disease even after treatment with chemotherapy and stem cell transplants.

Its getting to be a difficult situation, Gore said.

There are 3,100 cases of children with B-lineage ALL each year, he said.

B cells, also known as B lymphocytes, are white blood cells that produce antibodies, which fight infection. A characteristic of B cells is that they have a protein on their surface called CD19, which is the key to the new treatment.

The new process, marketed by Novartis and first developed at the University of Pennsylvania, involves harvesting T cells from the patient. Novartis then introduces DNA into these T cells, introducing new genes into the T cells, [which] include a receptor that will recognize CD19, Gore said. The genes that are fused into the T cells are manufactured in the lab but are copies of normal human genes, Gore said. The new cell is called a chimeric antigen receptor T cell, or CAR-T cell.

Normal T cells fight disease, and we know that T cells can attack cancer cells as well, but getting them to do so in the host where the cancer has developed is tricky, Gore said. Cancer cells are very similar [to] normal cells from which they derive.

Turning the T cells into CAR-T cells helps by targeting the CD19 marker on the B cells. CD19 happens to be a pretty good target for cancer technology because its only on B cells, Gore said. These new CAR-T cells latch onto the leukemia cells.

Reproducing cells

Then, once they see that theyre needed, the CAR-T cells are going to make more of themselves. Theyre going to make a whole army-full beside what we gave the patient, Gore said. Other genes in the introduced DNA give the immune system the go-ahead to kill these leukemia cells.

The CAR-T cells target both healthy and malignant B cells, but people live all the time without B cells, Gore said, by relying on drugs such as rituximab.

The treatment is not easy on the patient, however. When this massive influx of these new T cells attack all these leukemia cells, youre basically setting up a jihad in your body, Gore said. People can get very critically ill after this therapy, even needing to be treated in the intensive care unit.

Despite the hardship, the FDAs Oncologic Drugs Advisory Committee voted 10-0 on July 12 to recommend approval of CAR-T therapy, and it is very rare that an ODAC approval does not end up in an FDA approval, Gore said.

In one trial, 41 of 50 patients with relapsed or refractory B-lineage ALL each achieved complete remission after three months, Gore said, and 60 percent of those patients were still in remission six months later.

It will be rapidly opened up to adults as well, theres no question about it, he said. Some people think this therapy may replace stem cell therapy and doctors hope it can be given before a patient relapses, avoiding stem cell transplants.

We dont have long-term follow-up to know if these patients are cured, Gore said. Theyve certainly been rescued from otherwise-certain death.

Gore said the Yale School of Medicine has been approached by Novartis to be one of the rollout sites for this therapy.

While the new treatment targets a relatively rare cancer, its likely to be effective in other cancers involving B cells, including other types of leukemia and lymphoma, Gore said. (Not all lymphomas and leukemias are B cell cancers, however.) This rare leukemia has been the subject of all this investigation because CD19 is such a low-hanging fruit, because we can live without B cells, he said.

But the technology can theoretically be adapted to any kind of tumor, he said. Theoretically, you could make a CAR-T to target any particular kind of cancer provided that that cancer expresses certain proteins that are predominantly limited to the cancer and not important vital organs.

Call Ed Stannard at 203-680-9382.

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Rare leukemia targeted by modifying patients’ immune cells – New Haven Register

Researchers reprogram immune cells to treat psoriasis and more – SlashGear

A new study details the successful reprogramming of certain immune cells that could lead to treatments for autoimmune diseases like psoriasis. The work was performed by researchers with the Gladstone Institutes, and it is made possible by a small-molecule drug that essentially converts immune cells from the type that attack the body to the type that keep things in check. It could also prove effect for treating cancers.

Immune cells are known as T cells, and they come in two varieties: regulatory, which keeps the immune system from running rogue and attacking a healthy body, and effector, which trigger the immune system into action. Autoimmune disorders are the result of a dysfunction with these cells, often resulting in the body attacking some healthy part of itself, such as causing inflamed, scaly skin in the case of psoriasis.

Immune system dysfunction can go the other way, as well, resulting from a suppression of it that causes different sorts of diseases or cancers. Because these T cells are so greatly involved in the function of the immune system and its balance, it makes sense that tweaking the presence of these cells in the body could address diseases, and thats exactly what researchers have done for the first time ever.

Using the aforementioned drug, the potentially damaging effector cells can be reprogrammed into regulatory T cells, which would then bring the immune system under control and stop it from attacking a healthy body. It is thought that producing more regulatory T cells in the body could also keep the immune system from rejecting transplanted cells in the case of stem cell therapies.

As far as cancer is concerned, the drug could also be used to boost regulatory T cells so that the immune system can better find and attack cancer cells, the aim being to treat or prevent cancers. Future plans for this research werent stated, however, it is a milestone discovery that could lead to treatments for many diseases.

SOURCE: Nature, EurekAlert

Link:

Researchers reprogram immune cells to treat psoriasis and more – SlashGear

Genetic risk for lupus tied to ancestry – Medical Xpress

August 4, 2017 by Will Doss Credit: CC0 Public Domain

Northwestern Medicine collaborated with international colleagues in a study that identified two dozen new genes linked to lupus after analyzing genetic samples from over 27,000 individuals across the globe.

The study, published in Nature Communications, was co-authored by Rosalind Ramsey-Goldman, MD, DrPH, the Solovy/Arthritis Research Society Research Professor of Medicine in the Division of Rheumatology, part of a group of authors from more than 70 universities.

“These new observations will help direct future research to better diagnose and treat the disease while also providing insights into why lupus disproportionately affects certain ethnicities at higher rates and more severely,” said Ramsey-Goldman, also a member of the Robert H. Lurie Comprehensive Center Cancer and Northwestern University Clinical and Translational Sciences Institute.

Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women during their childbearing years, and is more common in African-American, Native American and Hispanic patients. In SLE, the immune system produces antibodies that cause inflammation and damage the body’s own organs and tissues, but it can be difficult to diagnose because its symptoms are similar to those of other immune system diseases.

The study revealed 24 genomic regions that contribute to an accelerating pattern of risk for SLE, leading the investigators to propose what they call the “cumulative hit hypothesis.”

According to the authors, an immune system can normally absorb the effect of a modest amount of these risky genes, but as the number of genes climbs the immune system becomes overwhelmedresulting in disorders such as SLE.

The ancestral distribution of these genes may explain the ethnic disparities in SLE, according to the study. One cluster of risky genes has a greater frequency in people with African-American ancestry, a population with a higher incidence of SLE. On the other hand, a different risky cluster was less common in those with a mix of African-American and Central European ancestry, reflecting how a complex demographic history can affect the risk of developing SLE.

“There is a genetic predisposition to developing lupus and this study will help scientists decipher the heterogeneous manifestations of the disease, which is hard to diagnose and treat,” Ramsey-Goldman said. “The hope is that these discoveries lead to better diagnostic tools, such as biomarkers, and assist in the development of targeted therapies.”

While large-scale population screening may not be financially practical, it may be more realistic to accelerate the diagnosis of suspected lupus by testing narrowly for genetic markers such as those uncovered in the current study, according to the authors.

“Understanding the implications and not just cataloguing the overlap of genetic variation that predicts multiple autoimmune diseases is a key next set of questions these investigators are pursuing,” said lead author Carl Langefeld, PhD, professor of Biostatistics at Wake Forest Medicine.

Explore further: Large multi-ethnic study identifies many new genetic markers for lupus

More information: Carl D. Langefeld et al. Transancestral mapping and genetic load in systemic lupus erythematosus, Nature Communications (2017). DOI: 10.1038/ncomms16021

Leading rheumatologist and Feinstein Institute for Medical Research Professor Betty Diamond, MD, may have identified a protein as a cause for the adverse reaction of the immune system in patients suffering from lupus. A better …

A new study by researchers from Brigham and Women’s Hospital in Boston, Massachusetts reveals that Asian and Hispanic patients with systemic lupus erythematosus (SLE) have lower mortality rates compared to Black, White, or …

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Genetic risk for lupus tied to ancestry – Medical Xpress

Big Data shows big promise in medicine – Livemint

Physicians arent likely to be replaced by algorithms, at least not right away, but their skill sets might have to change. Photo: iStock

In handling some life-or-death medical judgements, computers have already surpassed the abilities of doctors. Were looking at the promise of self-driving cars, according to Zak Kohane, a doctor and researcher at Harvard Medical School. On the roads, replacing drivers with computers could save lives that would otherwise be lost to human error. In medicine, replacing intuition with machine intelligence might save patients from drug side effects or otherwise incurable cancers.

Consider precision medicine, which involves tailoring drugs to individual patients. And to understand its promise, look to Shirley Pepke, a physicist who migrated into computational biology. When she developed a deadly cancer, she responded like a scientist and fought it using Big Data. And she is winning. She shared her story at a recent conference organized by Kohane.

In 2013, Pepke was diagnosed with advanced ovarian cancer. She was 46, and her children were nine and three years old. It was just two months after her annual gynaecological exam. She had symptoms, which the doctors brushed off, until her bloating got so bad she insisted on an ultrasound. She was carrying six litres of fluid caused by the cancer, which had metastasized.

She did what most people do in her position. She agreed to a course of chemotherapy. She also did something most people wouldnt know how to doshe started looking for useful data. After all, tumours are full of data. They carry DNA with various abnormalities, some of which make them malignant or resistant to certain drugs. Armed with that information, doctors design more effective, individualized treatments. Already, breast cancers are treated differently depending on whether they have a mutation in a gene called HER2. So far, scientists have found no such genetic divisions for ovarian cancers.

But there was some data. Years earlier, scientists had started a data bank called the Cancer Genome Atlas. There were genetic sequences on about 400 ovarian tumours. To help her extract information, she turned to Greg ver Steeg, a professor at the University of Southern California, who was working on an automated pattern-recognition technique called correlation explanation (CorEx). It had not been used to evaluate cancer, but she and Ver Steeg thought it might work. She also got genetic sequencing done on her tumour.

In the meantime, she found out she was not one of the lucky patients cured by chemotherapy. The cancer came back.

But CorEx had turned up a clue. Her tumour had something common with those of the luckier women who responded to the chemotherapyan off-the-charts signal for an immune system product called cytokines. She reasoned that in those luckier patients, the immune system was helping kill the cancer, but in her case, there was something blocking it.

Eventually she concluded that her one shot at survival would be to take a drug called a checkpoint inhibitor, which is geared to break down cancer cells defences against the immune system. At the same time, she went in for another round of chemotherapy.

The checkpoint inhibitor destroyed her thyroid gland, she said, and the chemotherapy was damaging her kidneys. She stopped, not knowing whether her cancer was still there or not. To the surprise of her doctors, she started to get better. Her cancer became undetectable. Still healthy today, she works on ways to allow other cancer patients to benefit from Big Data the way she did.

Kohane, the Harvard Medical School researcher, said similar data-driven efforts might help find side effects of approved drugs. Clinical trials are often not big enough or long-running enough to pick up even deadly side effects that show up when a drug is released to millions of people. Thousands died from heart attacks associated with the painkiller Vioxx before it was taken off the market.

Last month, an analysis by another health site suggested a connection between the rheumatoid arthritis drug Actemra and heart attack deaths, though the drug had been sold to doctors and their patients without warning of any added risk of death. Kohane suspects there could be many other unnecessary deaths from drugs whose side effects didnt show up in testing.

So whats holding this technology back? Others are putting big money into Big Data with the aim of selling things and influencing votes. Why not use it to save lives?

First theres the barrier of tradition, said Kohane, whose academic specialty is bioinformatics, a combination of math, medicine and computer science. Medicine does not understand itself as an information-processing discipline, he said. It still sees itself as a combination of intuitive leaps and hard science. And doctors arent collecting the right kinds of data. Were investing in information technology thats not optimized to do anything medically interesting, he said. Its there to maximize income but not to make us better doctors.

Physicians arent likely to be replaced by algorithms, at least not right away, but their skill sets might have to change. Already, machines have proven themselves better than humans in the ability to read scans and evaluate skin lesions. Pepke ended her talk by saying that in the future, doctors may have to think less statistically and more scientifically. Her doctors made decisions based on rote statistical information about what would benefit the average patientbut Pepke was not the average patient. The status quo is an advance over guessing or tradition, but medicine has the potential to do so much better. Bloomberg View

Faye Flam is a Bloomberg View columnist.

Comments are welcome at views@livemint.com

First Published: Tue, Aug 01 2017. 02 03 AM IST

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Big Data shows big promise in medicine – Livemint