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For stem cell treatments, patients, doctors, scientists, must collaborate – The San Diego Union-Tribune

Posted: April 20, 2017 at 8:44 pm

Stem cell research begins with scientists, passes on to physicians and ends up with patients.

But those roles arent as separate as they seem, said speakers Thursday at a special meeting held by the California Institute for Regenerative Medicine, the states stem cell agency, and UC San Diego.

The agency is beginning a statewide tour to discuss the progress of its treatments through the lengthy research and clinical trial process. One priority is to make sure all those involved understand each others needs, and how they can help.

Speaker David Higgins has multiple roles built into his life. A San Diegan with Parkinsons disease, Higgins sits on CIRMs governing board.

Patient input is heard throughout CIRM, Higgins said, addressing the audience of more than 100 at the Sanford Consortium for Regenerative Medicine on Torrey Pines Mesa.

Patient advocates sit on reviews for grant funding, Higgins said. Nothing ever goes out the door without it being screened through the eyes of a patient advocate.

Patients can now take a much more active role in managing their illness and advocate for others, Higgins said, because doctors now recognize that treating disease is a partnership.

Now were looking at a two-way relationship, Higgins said. I dont know a single physician that Ive ever talked to who doesnt welcome this, Higgins said.

And in the long run, nobody can escape patienthood, said Dr. Catriona Jamieson, an oncologist-researcher at UCSD Moores Cancer Center.

Were all going to be patients, were all going to be health care users, Jamieson said. I dont see the patient term as in any way stigmatizing, because its part of using our health care system.

Making sure these roles are harmonized is important to CIRM, which has about $800 million left of the $3 billion given by California voters in 2004 in Proposition 71.

And while CIRM cant formally lobby on the issue, those who support the agency recognize they need public support if they want more money from taxpayers.

Jamieson said CIRM has helped her research, her UCSD colleagues and patients by grants and funding alpha stem cell clinics, including one at UCSD. These clinics help translate science into patient care, and help scientists and doctors share ideas and resources.

What we know so far is that great medicine requires great science, said Jamieson, who specializes in blood cancers.

Audience member Adrienne Shapiro was there as a patient advocate for sickle cell disease. Shes a carrier of the trait, and her daughter, Marissa Cors, has the disease. CIRM has funded a program to develop a better bone marrow transplant to treat the disease.

Cors said one of her main issues is dealing with the pain sickle cell disease causes her.

The pain medications are really the key at this particular point in the journey, Cors said, hesitating slightly in discussing the course of her disease.

Cors said shes hopeful that the CIRM program helps others.

Im looking for something effective for the community, Cors said.

bradley.fikes@sduniontribune.com

(619) 293-1020

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UNC researchers ID cell where HIV persists despite treatment, new target for cure research – News & Observer

Posted: April 20, 2017 at 8:44 pm


News & Observer
UNC researchers ID cell where HIV persists despite treatment, new target for cure research
News & Observer
But researchers in the Division of Infectious Diseases at the UNC School of Medicine have found that the virus still persists in HIV-infested macrophages large white blood cells found in tissues throughout the body, including the liver, lungs, bone ...

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Immune cells play surprising role in steady heartbeat – Science News

Posted: April 20, 2017 at 8:44 pm

Immune system cells may help your heart keep the beat. These cells, called macrophages, usually protect the body from invading pathogens. But a new study published April 20 in Cell shows that in mice, the immune cells help electricity flow between muscle cells to keep the organ pumping.

Macrophages squeeze in between heart muscle cells, called cardiomyocytes. These muscle cells rhythmically contract in response to electrical signals, pumping blood through the heart. By plugging in to the cardiomyocytes, macrophages help the heart cells receive the signals and stay on beat.

Researchers have known for a couple of years that macrophages live in healthy heart tissue. But their specific functions were still very much a mystery, says Edward Thorp, an immunologist at Northwestern Universitys Feinberg School of Medicine in Chicago. He calls the studys conclusion that macrophages electrically couple with cardiomyocytes paradigm shifting. It highlights the functional diversity and physiologic importance of macrophages, beyond their role in host defense, Thorp says.

Matthias Nahrendorf, a cell biologist at Harvard Medical School, stumbled onto this electrifying find by accident.

Curious about how macrophages impact the heart, he tried to perform a cardiac MRI on a mouse genetically engineered to not have the immune cells. But the rodents heartbeat was too slow and irregular to perform the scan.

Immune cells called macrophages (green) squeeze in between heart cells (red) in an area of the heart called the atrioventricular node, as seen in this reconstruction of a human AV node. This node is a cluster of muscle fibers that electrically connects the upper and lower chambers of the heart.

These symptoms pointed to a problem in the mouses atrioventricular node, a bundle of muscle fibers that electrically connects the upper and lower chambers of the heart. Humans with AV node irregularities may need a pacemaker to keep their heart beating in time. In healthy mice, researchers discovered macrophages concentrated in the AV node, but what the cells were doing there was unknown.

Isolating a heart macrophage and testing it for electrical activity didnt solve the mystery. But when the researchers coupled a macrophage with a cardiomyocyte, the two cells began communicating electrically. Thats important, because the heart muscle cells contract thanks to electrical signals.

Cardiomyocytes have an imbalance of ions. While in the resting state, there are more positive ions outside the cell than inside, but when a cardiomyocyte receives an electrical signal from a neighboring heart cell, that distribution switches. This momentary change causes the cell to contract and send the signal on to the next cardiomyocyte.

Scientists previously thought that cardiomyocytes were capable of this electrical shift, called depolarization, on their own. But Nahrendorf and his team found that macrophages aid in the process. Using a protein, a macrophage hooks up to a cardiomyocyte. This protein directly connects the inside of these cells to each other, allowing macrophages to transfer positive charges, giving cardiomyocytes a boost kind of like with a jumper cable. This makes it easier for the heart cells to depolarize and trigger the heart contraction, Nahrendorf says.

With the help of the macrophages, the conduction system becomes more reliable, and it is able to conduct faster, he says.

Nahrendorf and colleagues found macrophages within the AV node in human hearts as well but dont know if the cells play the same role in people. The next step is to confirm that role and explore whether or not the immune cells could be behind heart problems like arrhythmia, says Nahrendorf.

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HER2-Specific CAR T-Cell Therapy Active in Progressive Glioblastoma – Cancer Network

Posted: April 20, 2017 at 8:44 pm

Administration of autologous HER2-specific chimeric antigen receptor (CAR)-modified virus specific T Cells (VSTs) was safe and had clinical benefit for some patients with progressive glioblastoma, a disease with limited effective therapeutic options.

Results of a small phase I study of this monotherapy were published in JAMA Oncology, by Nabil Ahmed, MD, MPH, of Baylor College of Medicine in Houston, and colleagues.

CAR T-cell therapies are an attractive strategy to improve the outcomes for patients with glioblastoma, they wrote. In our study, we infused HER2-CAR VSTs intravenously because T cells can travel to the brain after intravenous injections, as evidenced by clinical responses after the infusion of tumor-infiltrating lymphocytes for melanoma brain metastasis and by detection of CD19-CAR T cells in the cerebrospinal fluid of patients with B-precursor leukemia.

The study included 17 patients with progressive HER2-positive glioblastoma (10 patients aged 18 or older; 7 patients younger than 18). Patients were given one or more infusions of autologous VSTs specific for cytomegalovirus, Epstein-Barr virus, or adenovirus and genetically modified to express HER2-CARs. Six patients were given multiple infusions.

Infusions were well tolerated with no dose limiting toxicities presenting. Two patients had grade 2 seizures and/or headaches, which the researchers wrote were probably related to the T-cell infusion.

Although HER2-CAR VSTs did not expand, they were detected in the peripheral blood for up to 12 months after the infusion.

Although we did not observe an expansion of HER2-CAR VSTs in the peripheral blood, T cells could have expanded at glioblastoma sites. At 6 weeks after T-cell infusion, the MRI scans of patients 3, 7, 10, 16, and 17 showed an increase in peritumoral edema, the researchers wrote. Although these patients were classified as having a progressive disease, it is likely that the imaging changes for some of these patients were due to inflammatory responses, indicative of local T-cell expansion, especially since these patients survived for more than 6 months.

Only 16 of the 17 patients were evaluable for response. Patients underwent brain MRI 6 weeks after T-cell infusion. One patient had a partial response for longer than 9 months and seven patients had stable disease for between 8 weeks to 29 months. Three patients with stable disease are alive without any evidence of progression from 24 to 29 months of follow-up. Eight patients progressed after the infusion.

The median overall survival was 11.1 months from the first T-cell infusion and 24.5 months from diagnosis.

The researchers noted that the inclusion of children in the study, who have a better prognosis than adults, may have affected the results; however, there was no significant difference between the survival probability for children and that for adults in this clinical study.

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PolarityTE (COOL) Signs Manufacturing Agreement with Cell Therapy and Regenerative Medicine – StreetInsider.com

Posted: April 20, 2017 at 8:44 pm

News and research before you hear about it on CNBC and others. Claim your 2-week free trial to StreetInsider Premium here.

PolarityTE, Inc. (NASDAQ: COOL) announces the signing of a manufacturing agreement with Cell Therapy and Regenerative Medicine at the University of Utah School of Medicine. CTRM is the established manufacturer of hematopoietic stem cell transplants for renowned institutions of the Salt Lake region such as the Huntsman Cancer Institute and Primary Children's Hospital. In addition, CTRM manufactures a variety of regenerative medicine products, is FACT accredited, and has technical expertise in current Good Tissue Practice (cGTP) and current Good Manufacturing Practice (cGMP).

Denver Lough, MD, PhD, Chairman and CEO, stated, "This agreement with CTRM should provide PolarityTE with rapid clinical translation of the promising products we are developing, and takes us one step closer to achieving our goal of clinical application of our launch product, SkinTE. As we prepare for market entry in 2018, our established relationship with CTRM creates a springboard for the anticipated scale-up to address the large burn and chronic wound markets, with the pursuit of our own independent manufacturing facility. Plans are solidifying for a unique solution to both commercial and emergent relief manufacturing of SkinTE and future Polarity products. Our goal is not only to meet demand, but also to be able to deliver promptly around the globe when urgent response is needed."

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Novartis CAR-T Cell Therapy Receives FDA Breakthrough … – Pharmaceutical Processing

Posted: April 20, 2017 at 8:44 pm

Novartis CAR-T cell therapy CTL019 receives FDA Breakthrough Therapy designation for treatment of adult patients with r/r DLBCL.

Novartis announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to CTL019, an investigational chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of adult patients with relapsed and refractory (r/r) diffuse large B-cell lymphoma (DLBCL), who have failed two or more prior therapies.

This is the second indication for which CTL019 has received this designation; the first being for the treatment of r/r B-cell acute lymphoblastic leukemia (ALL) in pediatric and young adult patients.

"At Novartis, we are eager to unlock the full potential of CTL019, including the potential to help patients with r/r DLBCL," said Vas Narasimhan, Global Head of Drug Development and Chief Medical Officer, Novartis. "We look forward to working closely with the FDA to help bring this potential new treatment option to patients as soon as possible."

CAR-T cell therapy is different from typical small molecule or biologic therapies currently on the market because it is manufactured for each individual patient. During the treatment process, T cells are drawn from a patient's blood and reprogrammed in the laboratory to create T cells that are genetically coded to hunt the patient's cancer cells and other B-cells expressing a particular antigen.

CTL019 was first developed by the University of Pennsylvania (Penn). In 2012, Novartis and Penn entered into a global collaboration to further research, develop and then commercialize CAR-T cell therapies, including CTL019, for the investigational treatment of cancers. Through the collaboration, Novartis holds the worldwide rights to CARs developed with Penn for all cancer indications.

In March 2017, Novartis announced that the FDA accepted the company's Biologics License Application filing and granted priority review for CTL019 in the treatment of r/r pediatric and young adult patients with B-cell ALL.

The Breakthrough Therapy designation is based on data from the multi-center phase II JULIET study (NCT02445248), which is evaluating the efficacy and safety of CTL019 in adult patients with r/r DLBCL. JULIET is the second global CAR-T trial, following the Novartis ELIANA study (NCT02435849) investigating CTL019 in r/r B-cell ALL. Findings from JULIET are expected to be presented at an upcoming medical congress.

"We are encouraged by the FDA's recognition in the potential of CTL019 for this indication, which follows our promising studies of this therapy for ALL and the FDA filing by Novartis in pediatric and young adult ALL that received priority review," said the Penn team's leader, Carl June, M.D., director of the Center for Cellular Immunotherapies in the Perelman School of Medicine at the University of Pennsylvania. "Work with our collaborators at trial sites across the world is paving a path to bring personalized cell therapies to more patients with these devastating blood cancers."

According to FDA guidelines, treatments that receive Breakthrough Therapy designation are those that treat a serious or life threatening disease or condition and demonstrate a substantial improvement over existing therapies on one or more clinically significant endpoints based on preliminary clinical evidence. The designation also indicates that the agency will expedite the development and review of CTL019 in adults with r/r DLBCL.

This marks the 14thBreakthrough Therapy designation for Novartis since the FDA initiated the program in 2013, underscoring an emphasis to develop innovative treatments in disease areas with significant unmet need.

DLBCL is the most common form of lymphoma and accounts for approximately 30 percent of all non-Hodgkin lymphoma cases1. Ten to 15 percent of DLBCL patients fail to respond to initial therapy or relapse within three months of treatment, and an additional 20 to 25 percent relapse after initial response to therapy2.

Because CTL019 is an investigational therapy, the safety and efficacy profile has not yet been established. Access to investigational therapies is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the therapy. Because of the uncertainty of clinical trials, there is no guarantee that CTL019 will ever be commercially available anywhere in the world. ____________________________________________________

References:

1 American Society of Clinical Oncology. Lymphoma - Non-Hodgkin: Subtypes (Dec. 2016 revision).http://www.cancer.net/cancer-types/lymphoma-non-hodgkin/subtypes. Accessed March 2017.

2 Sehn, L. Paramount prognostic factors that guide therapeutic strategies in diffuse large B-cell lymphoma. Hematology, December 2012; 1; 402-409.

(Source: GlobeNewswire)

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Diabetes control tied to heart stent outcomes – WHTC

Posted: April 20, 2017 at 8:43 pm

Thursday, April 20, 2017 5:03 p.m. EDT

By Will Boggs MD

(Reuters Health) - For people with type 2 diabetes, maintaining good blood sugar control in the years after receiving a coronary artery stent is associated with a lower risk of heart attack and stroke, according to a recent study.

Although intensive glucose control had no benefit on the rate of major cardiovascular events in previous studies, our data suggest that strict glucose control after PCI (heart catheterization) can improve long-term clinical outcomes in diabetic patients, Dr. Joo-Yong Hahn from Samsung Medical Center in Seoul told Reuters Health.

Heart disease is the major cause of death among people with type 2 diabetes, Hahns team writes in Circulation: Cardiovascular Interventions. Although intensive blood sugar control is known to reduce damage to tiny blood vessels that are involved in many of the nerve and circulatory effects of diabetes, its not clear if the same is true for major arteries such as the ones that carry blood to the heart.

The researchers studied 980 patients with type 2 diabetes who had undergone percutaneous cardiac intervention (PCI) to clear a blocked coronary artery and place a supportive mesh tube known as a stent. Hahns team followed the patients health for up to seven years.

They looked at long-term blood sugar control using a measurement known as hemoglobin A1c (HbA1c or A1C), and used it to compare the patients risks of death, heart attack, repeat catheterizations and stroke over the study period.

The researchers defined good control as an A1C score below 7.0 and poor control as A1C of 7.0 or higher. Then they matched patients according to other risk factors and ended up with 322 pairs of patients for comparison.

In the overall group of 980 patients, the risk of all bad outcomes was 25 percent lower with good blood glucose control than with poor blood glucose control.

In the matched comparison, some 37 percent of patients with poor control had bad outcomes (heart attack, stroke, and so on) over the next seven years, versus less than 28 percent of patients with good control. Most of the difference in bad outcomes between the groups resulted from a higher rate of repeat stenting in the group with poor blood glucose control.

PCI is not the end of treatment for coronary artery disease, Hahn said by email. Optimal medical treatment, including glycemic control, is a cornerstone therapy after PCI, he said.

The effects of glucose control in type 2 diabetes may differ according to patient characteristics, such as recent cardiovascular events, baseline glycemic control status and duration of diabetes, Hahn added.

The researchers write that more study is needed before they can conclude strict glucose control after stenting will improve long-term clinical outcomes in people with diabetes.

Its important to underscore the message of good glycemic control, said Dr. Azfar G. Zaman from Newcastle University in the UK. He was not involved in the study but has done similar research. In patients with PCI there is evidence to support better outcomes and need for fewer interventions, Zaman said by email.

This is a single center study with limited numbers, but the findings support data from other studies, he noted.

SOURCE: http://bit.ly/2pjU0al Circulation: Cardiovascular Interventions, online April 3, 2017.

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Good 4 You: Mental fitness for diabetes – WOAI

Posted: April 20, 2017 at 8:43 pm

by Delaine Mathieu, News 4 San Antonio

Good 4 You: Mental fitness for diabetes

There's a unique new therapy group in San Antonio designed to help people living with diabetes cope with the disease. It's called Mental Fitness for Diabetes. The goal of the program is to help treat mental side-effects that come along with diabetes. "I remember when I was diagnosed with diabetes," said Sarah Villegas. "March 31 for 2016. So, it's been a year."

The 71-year-old registered nurse was completely surprised when she was diagnosed with type two diabetes. "When the doctor came in and showed me my lab results," she explained. "I looked at the paper and I said, are you kidding me?"

Villegas lost seventeen pounds and got her condition under control. When she heard about this new mental fitness group, she was pleasantly surprised. "Never in my 49 years as a registered nurse -- to combine diabetes, a major chronic illness with a major mental health illness, which is chronic, and put them together -- that is an awesome concept," she said.

Valerie Moczgemba, with Alamo Wellness Group, will be running the sessions. "A lot of times, people who have been diagnosed with diabetes experience depression anxiety," she said. "There also may be anger or irritability. She said they'll be focusing on disease management and how mental health symptoms play into disease management.

Villegas says it's high time a treatment like this is made available for people with diabetes. "It cannot be ignored," she said. "We need to address their physical health issues as well as the mental issues. They both go hand-in-hand."

April 30th is the last day to register. If you're interested in signing up, go to alamowellnessgroup.com.

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Researchers discover technique that could lead to diabetes cure – FOX 29

Posted: April 20, 2017 at 8:43 pm

by Zack Hedrick, Fox San Antonio

Researchers discover technique that could lead to diabetes cure

SAN ANTONIO Doctors in San Antonio have made a breakthrough discovery which could mean a potential cure for people with diabetes.

Tom Mathieu is a fanatical bike rider.

He believes he's pedaled more than 20,000 miles since he began riding in his early thirties.

He started riding because of a condition he was diagnosed with as a teenager.

Doctors told me it'd be a miracle that you see 60," said Mathieu.

Mathieu is a type 1 diabetic and his doctors tell him his body produces zero insulin.

He and his doctors believe his bike riding has helped keep his diabetes in check.

Well I'm 73 and I've had [diabetes] since I was 14," said Mathieu.

Researchers at UT Health San Antonio have discovered a strategy that could mean a cure.

It's a game changer, said Dr. Bruno Doiron. It change drastically the life of a patient that's diabetic."

Using a technique called gene transfer, doctors can alter other cells so they start to secrete insulin but only in response to sugar.

"Im using already what's naturally in your body," said Dr. Doiron.

The University Health System says diabetes is the 4th leading cause of death in Bexar County.

Mathieu calls the potential therapy revolutionary.

He says diabetes is a condition that requires discipline, but says this discovery would give a lot of freedom back to people dealing with diabetes.

People won't be burdened by what diabetes causes and then the cost of those causes, said Mathieu. I think it's miraculous."

Doctors say the therapy has cured diabetes in mice for one year without any side effects, which has never been done.

The goal is to conduct large-animal studies and human clinical trials in the next three to five years.

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Family members of diabetes patients plead for law to limit … – Las Vegas Review-Journal

Posted: April 20, 2017 at 8:43 pm

CARSON CITY Patients and family members of those who suffer from diabetes shared stories of struggle and heartbreak Wednesday and urged support for a bill to rein in the escalating costs of diabetes medication.

Bonnie Sedich knows the pain all too well. Four of her five children were diagnosed with juvenile diabetes. There was no family history. Two children died when in adulthood. Two others live with the disease.

One son, Jeffrey, was diagnosed at age 3. His body was found in a rural California region in 1981, a bottle of insulin by his side. He died at 19.

Another daughter, Elizabeth, was diagnosed when she was 8. She died in November at 51 of complications from the disease. Over the years, the cost of her drugs skyrocketed from about $10 a bottle to more than $300. Toward the end, she was paying more than $2,100 a month if she could afford it, Sedich said.

If you cant afford your diabetes medications then you just suffer and die, Sedich said.

She and others spoke at a press conference to urge support for Senate Bill 265. Sponsored by state Sen. Yvanna Cancela, D-Las Vegas, the bill would establish a list of insulin-related diabetic products to be treated as essential medications. It also would create a refund when insulin costs exceed the medical consumer price index.

The bill would require drug makers to divulge how prices are set, including the cost of medications, as well as amounts spent on marketing and research. It would set registration and reporting requirements on pharmaceutical sales representatives.

Diabetes is a serious disease that affects people for a lifetime, Cancela said. Medical costs are twice as high for people with diabetes.

Deadly and common

Diabetes is the eighth-leading cause of death in Nevada, where 12.4 percent of adults have the disease and 38 percent are pre-diabetic, she said.

Senate Majority Leader Aaron Ford, D-Las Vegas, is one of those who have been determined to be pre-diabetic. He said he received he diagnosis about a year ago.

Diabetes has become one of the largest public health crises in our time, and the medication to treat this disease must be affordable and accessible, he said. In this time of crisis, we have to come together.

Keyonna Lawrence said she was diagnosed as diabetic three years ago. A personal care assistant, she tries to control the disease through diet, and she stretches mediations when she can afford it by taking a half-dose.

My biggest fear is my 11-year-old son is going to wake up, say, Mom? and Moms as cold as ice, Lawrence said.

SB265 was granted an exemption and waiver from deadlines and remains pending in the Senate.

Contact Sandra Chereb at schereb@reviewjournal.com or 775-461-3821. Follow @SandraChereb on Twitter.

Sen. Yvanna Cancela, sponsor of Senate Bill 265, said diabetes care cost Nevadans about $2.4 billiion annually in medical costs.

Over the last 20 years, vials of the most commonn insulin products have gone from $17 to $138; and $21 to $255.

According to the American Diabetes Association, 281,355 people in Nevada, or 12.4 percent of the adult population, have diabetes. Another 787,000, or 38.5 percent of the adult population are pre-diabetic with blood glucose levels higher than normal.

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