Category Archives: Arizona Stem Cells

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Travel ban in the courts In the latest arguments over President Donald Trumps travel ban, a three-judge panel of a federal appeals court in Seattle indicated Monday it would continue allowing grandparents and other relatives of U.S. residents to travel to the U.S. from six predominantly Muslim countries. But the judges were less forthcoming about their views on exceptions to a second part of the ban, suspending the nations refugee program. In July in a provisional ruling, the Supreme Court allowed exceptions to the ban for many relatives but not for most refugees. The Supreme Court will hear arguments in the case in October.

Stem cell clinic crackdown The Food and Drug Administration announced a crackdown on dangerous stem cell clinics Monday, while pledging to ease the path to approval for companies and doctors with legitimate treatments in the field. The agency reported actions against two large stem cell clinics and a biotech company, saying it was critical to shut down unscrupulous actors in regenerative medicine, which includes stem cell and gene therapies and immunotherapies. Stem cells can develop into many different types of cells, and are thought to have the potential to repair or replace damaged tissue. But the FDA has approved only a few stem-cell products.

Trump timed Arpaio pardon for storm ratings President Donald Trump offered a fiery defense Monday of his decision to pardon former Arizona Sheriff Joe Arpaio as Hurricane Harvey made landfall in Texas last week and claimed he timed it to attract maximum attention as television viewers were glued to storm coverage. Trump also suggested the Justice Department had political motives during the Obama administration for charging the former sheriff in a case concerning his illegal profiling of Hispanics. Actually, in the middle of a hurricane, even though it was a Friday evening, I assumed the ratings would be far higher than they were normally, Trump said.

European migrant influx Measures intended to stop migrants from trying to cross the Mediterranean were at the center of discussions in Paris among four European leaders who met with the leaders of three African countries Monday. The meeting, billed as a minisummit, brought together the leaders of France, Germany, Italy and Spain as well as Chad and Niger and one of Libyas leaders. Chad and Niger are transit countries for people fleeing war or poverty, while Libya is a departure point for crossing the Mediterranean and a center for traffickers who promise to get people to Europe.

Kenyas strict plastic bag ban Kenya will now punish with up to four years in jail anyone making, selling or importing plastic bags, putting in place one of the worlds toughest bans on the ubiquitous item that is blamed for clogging oceans and killing marine life. The rule, announced in March and put into effect Monday, also means garbage bags will be taken off supermarket shelves and visitors entering Kenya will be required to leave duty-free shopping bags at the airport. Kenya joins more than 40 other countries including China, the Netherlands and France that have introduced taxes on bags or limited their use.

German nurse suspect in 86 deaths A German nurse serving a life sentence for murdering two of his patients is believed to have killed at least 86 people entrusted to his care, officials said Monday, in what they described as an imagination-defying series of crimes. The nurse, identified as Niels Hoegel, was sentenced to life in February 2015, after a court found him guilty of administering overdoses of heart medication to some patients in an intensive care ward where he worked from 1999 to 2001. He was convicted of two counts of murder, two counts of attempted murder and causing bodily harm to patients and is serving his sentence. During his trial, the former nurse confessed to intentionally inducing cardiac crises in 90 of his patients, 30 of whom he said had died. That prompted officials to launch an investigation into the deaths of some 130 of Hoegels former patients. The results were presented Monday in Oldenburg. Authorities are waiting for the results of 41 toxicology reports, the results of which could drive the number of confirmed deaths even higher

Indian guru rape sentencing An Indian court sentenced a well-known guru to at least 10 years in prison for rape Monday, three days after followers angered by his conviction engaged in violent protests. Gurmeet Ram Rahim Singh was found guilty Friday of having raped two women more than a decade ago. Thousands of Singhs followers had gathered in the state where the verdict was announced. They responded by smashing cars, setting fire to buildings and attacking police officers, and the violence later spread to other cities in northern India. At least 38 people were killed, and more than 250 were injured.

Border dispute in Asia India and China agreed Monday to back away from their confrontation over a tiny slice of territory high in the Himalayas, easing tensions between the worlds two most populous countries. Both sides agreed to give some ground in order to end the standoff. In a short statement, the Indian government said it had reached an understanding with Beijing. China seemed willing to compromise but still claims the territory.

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Around the world - Bend Bulletin

The stem cell wizards of ASUs Brafman Lab. Left to right: Sreedevi Raman, Josh Cutts, Nick Brookhouser and Christopher Potts. Photo by Marco-Alexis Chaira/ASU Download Full Image

If you guessed through the use of pluripotent stem cells so named because they have the ability to turn into other types of cells then youre right on the money.

ASUs Brafman Labis on the cutting edge of this branch of research, recently earning a $1.5 million grant from the National Institutes of Health to study the mechanisms of early human neurodevelopment, and $225,000 from the Arizona Biomedical Research Commission to study the effects of aging and other risk factors for Alzheimers Disease.

Biomedical engineering Assistant Professor David Brafman, who heads the laboratory, credits his graduate students as crucial in securing these grants

The graduate students hard work, creativity and dedication were critically important for generating the data to convince the reviewers that our approach was feasible and worth funding, Brafman says of his students. Too often the success of a lab is attributed to the [principal investigator] when it is the postdocs, grad students and research technicians who are down in the trenches doing the work.

Graduate students from the Brafman Lab reviewing data. Photo by Marco-Alexis Chaira/ASU

The students working in the Brafman Lab often labor late into the night and sometimes on the weekend. They possess a special mix of a passion for their work and the knowledge that achieving potentially life-altering outcomes dont come with a simple nine-to-five job.

The laboratory they work in combines developmental biology, genetic engineering and bioinformatics to investigate the various factors that can govern a stem cells fate. If they can figure out the mechanisms behind the stem cells multipotential futures, they could use that information to design targeted therapies for ailments like idiopathic pulmonary fibrosis, heart failure and Alzheimers Disease.

Take Josh Cutts, who is pursuing his doctoral degree in biomedical engineering. He knows a thing or three about working in the Brafman Lab. Hes addicted to the thrill of discovery, regardless of any challenges or obstacles that may come his way.

Were working on things that havent been done before so its challenging sometimes frustrating to complete certain experiments or understand the results, he said.

The shapeshifting nature of the stem cells can make working with them seem like biological wizardry. In the lab the research team has made stem cells into brain cells, heart cells, lung cells and more.

Now we are working with cutting-edge brain organoids known colloquially as mini brains, which sounds a little eerie, to address many different research questions, said Cutts, who earned his bachelors and masters degrees in biomedical engineering at California Polytechnic State University, San Luis Obispo. Its miraculous to work with these every day.

Cutts work generated the preliminary data that helped the lab secure the NIH grant. After finishing his graduate work, this pluripotent scholar plans to earn a post doctorate degree to expand his knowledge and expertise. Long term, he hopes to contribute to translating stem cell technology to patients, in academia or industry.

Researcher Nick Brookhouser is working toward his doctorate in clinical translational sciences at the University of Arizonas College of Medicine in Phoenix. His research in the Brafman Lab is focused on Alzheimers Disease and investigating the contribution of the Apolipoprotein E gene, or APOE, towards the diseases progression.

He has successfully generated a set of stem cell lines from Alzheimers patients as well as other stem cell lines that serve as the control group in his research. He is currently working with gene editing techniques to investigate APOEs relationship to Alzheimers.

Brookhousers work is also supported by an Arizona Biomedical Research Commission grant. He developed patient-specific pluripotent stem cell lines and brain cell lines, and with those lines he created a 3-D neural culture system that models a brain for study. He has also been involved in testing and optimizing gene editing technologies.

In the future, he hopes to transition to more clinical-based research in the biotechnology industry. Long term he hopes to contribute to the development of cell-based therapies and work in clinical trials.

Doctoral student Sreedevi Raman has also been working on research related to Alzheimers Disease. Instead of experimenting with stem cells at their genesis, Raman is trying to make them old. She is intentionally accelerating the aging process of cells in a dish so that they may be used to model various age-related disorders.

Her work with induced pluripotent stem cells specifically has helped the Brafman Lab attain the ABRC grant. Raman can take adult stem cells and program them back into state where their fate is not yet assigned.

Christopher Potts, a research specialist with a professional science masters degree from ASU, works with gene editing. His contribution to the team is comparable to using copy and paste for genes, but a bit more complicated. Hes using technologies like CRISPR (Clustered regularly interspaced short palindromic repeats) to edit stem cell genomes.

I am changing the DNA of stem cells. Thats pretty cool, right? Potts said. I think one of the coolest things about our lab is how each student has their own project and functions basically independently, but we all help each other and are able to do much more than we could on our own.

Hes enjoying his research, but also looks forward to teaching a new generation of students in the future. He has a masters degree in science education and taught high school for four years before joining the lab.

Potts has aspirations of starting a new line of scientists through a, career in outreach or other high-level science education.

The cells he works on use signaling pathways to regulate what they will become like his multiple career options. Right now, I am just hoping for some signals to help me differentiate, he said.

Just as Brafman relies on the hard work of his students, the entire lab team relies on one another to succeed.

Our lab is pretty close-knit. We like to hang out together to socialize and I think that support system makes our lab more effective, Cutts said. If any of us are having a hard time with experiments or anything at all, you can rely on your lab members and especially [Brafman] to help you work it out.

Like Cutts, Brookhouser values the highly collaborative environment in the lab that has fostered strong professional relationships as well as lasting friendships.

Just as patient somatic cells can be reprogrammed to a pluripotent state, I feel that the skills and mentorship I have gained in this lab have allowed me to reach a pluripotent state and primed me to differentiate down many different career paths in the future, Brookhouser said.

Raman credits her positive collaborative learning experiences in the lab with helping her to make advances in research as well as open career possibilities for her future. Since she just started her doctoral work, shes got a lot of research ahead of her. Luckily, she found a good place to start.

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ASU grad students' lab skills help earn funding for cutting-edge biomedical research - Arizona State University

Most nights, Marcia Dunlap attaches seven or eight leeches around her husband John's eyes as part of an effort to restore some of his vision. Tom Bailey/The Commercial Appeal

With the help of his wife Marcia, John Dunlap receives his nightly leech treatment at his home in East Memphis. Marcia places several leeches on his face in an effort to increase pressure in his left eye. In conjunction with stem cell treatment, the Dunlaps hope that one day John may be a viable candidate for a procedure that could return some of his vision.(Photo: Jim Weber/The Commercial Appeal)

At home most evenings, Memphis, Tennessee, attorney John Dunlap, 80, unbuttons and removes his white dress shirt and counting his steps and remembering which way to turn carefullywalks with a tall white canefrom the living room to the dining table, where his wife Marcia has a plastic container of leeches.

Twenty-six months ago,the couple's schizophrenic sonAndrewattacked them in theirhome. The injuries blinded Dunlap. He's in total darkness.

After drapinga large, peach-colored towel around John's neck, Marcia reaches into the water for the skinniest leeches. Those are the hungriest and most likely to latchonto John's face.

One at a time, she gently presses four leeches to the skin around John's left eye and three around the right. She waits patiently wait for eachto bite and stay connected to John's skin.

"You can feel a bite,'' he says. "A little, stinging bite... And then after awhile you don't feel anything.''

The Dunlaps have carried out this unusualroutine60 or so times since December. It's a type of therapy prescribed by a Los Angeles doctor who offers experimental stem cell therapy designed to regenerate tissue.

"In the beginning he made it very clear he's not anophthalmologist and not an eye surgeon but he had had some success with stem cells in treating blindness. It's experimental,'' Dunlap said.

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The doctor prescribed the leech therapy as a preliminary step because, Dunlap said, the leech enzymesenhance the blood supply to the eye and nourishthe eye tissue.

The left eye had atrophied, or withered. The idea wasto restore health to the eyebefore the stem cell treatment. There is no right eye, but the hope is that the leech enzymes will help revive that optic nerve in case a transplant is ever possible.

Since the leech therapy,the pressure in the right eye has improved significantly, Dunlapsaid, referring to follow-upexams. The retina, which had folded into an ice-cream cone shape after the trauma, has begun returning to its normal shape, he said.

Even though he still cannot see out of the left eye and the optic nerve remains severed from the retina, Dunlap said, "I now have a live eye.''

The Dunlaps decline to identify the California doctor, describing him as a"humble'' person whodoes not seek the publicity.

With the help of his wife Marcia, John Dunlap receives his nightly leech treatment at his home in East Memphis. Marcia places several leeches on his face in an effort to increase pressure in his left eye. In conjunction with stem cell treatment, the Dunlaps hope that one day John may be a viable candidate for a procedure that could return some of his vision.(Photo: Jim Weber/The Commercial Appeal)

Andrew, the Dunlaps' mentally ill son, is charged with attempted murder and domestic assault, and remains in jail awaiting trial. Thecouplehave told authorities that they mainly want Andrew to receive mental health treatment.

The Dunlapshave experienced tragedy long before the 2015 assault.

Their son Jeff, one of four children, was a St. Jude Children's Research Hospital patient who died of cancer at age 10, in September 1974.

Dunlap recalls a return car tripfrom Knoxville, where he and Marcia had been visiting grandchildren shortly after he was released from rehab.

"As we were driving back I started thinking of all the things I won't get to do again. In my mind, I was going down the list,'' he said.

It would be a long list, including some leisure activities he loves. An avid Cubs fan, heenjoyed attending spring training games in Arizona. A passionate golfer, he enjoyedwatching how the ball flew when he struck it well.

But Dunlap stopped himself from completing the list of losses, telling himself, " 'You don't want to dwell on that'. . . It's as if the Lord sent me a message that hit me across my forehead, saying, 'John, get over it. It could be a whole lot worse.'

"Anytime I want to start thinking about the things I'm missing or not doing what I used to do, I think 'Get over it. Move on'.''

Sudden blindness is such a change in lifestyle. "I guess some people may feel the world has ended for them, but it hasn't,'' he said.

Marcia Dunlap gets special leeches for her husband John's nightly treatment from the laundry room where she keeps it out of sight. Marcia places several leeches on his face in an effort to increase pressure in his left eye. In conjunction with stem cell treatment, the Dunlaps hope that one day John may be a viable candidate for a procedure that could return some of his vision.(Photo: Jim Weber/The Commercial Appeal)

The stem cell and leech therapy is expensive and not covered by health insurance. Some have expressed their skepticism about the legitimacy of the experimental treatments.

"You have some people who are concerned for you, that your approach is not going to be effective,'' Dunlap said.

"Yet, several folks up herehave said, 'John, I'd take a shot at it. It is expensive but you're the one with the white cane and the one who is blind and has to live with it. You have everything to gain and nothing to lose.'''

While some might be concerned about the unusual treatments, many others are inspired by the Dunlaps,saidBlanche Tosh, a fellow church member and friend since high school.

"I have told them so many times, 'You just can't begin to know the lives you have affected,'' Tosh said.

"I know so many people who look at the way they are dealing with multiple things. How could anybody endure that and just go on and be pleasant and make it from day to day with the consistent attitude that the world sees.

"You are not going to find many people whoever see one of them without a smile,'' Tosh said.

She was inspired to start a gofundme account (gofundme.com/johndunlapvision) to help coverthe Dunlaps' expenses. As of midweek, $8,795 of the $100,000 goal had been raised.

Memphis lawyer John Dunlap and his wife Marcia continue to search for some medical procedure to restore at least partial vision after John was blinded a few years ago when their mentally ill son attacked him. (Photo: Jim Weber/The Commercial Appeal)

Since December, Dunlap has undergone two-and-a-half rounds of leech therapy and two series ofstem cell treatments. The couple traveled to California in June for the most recent stem cell procedures, and returned home with stem-cell eye drops and injections.

Nowthey are in the middle of the leech therapy they resumed this summer.

John has a follow-up exam next week, when he will learn if there's been continued progress from the stem cell and leech therapies.

The California doctor "indicated it would take two to three months to see if we were getting any results from stem cell therapy out there,'' Dunlap said. That time could come sometime this month or in September.

If the stem cell therapy has not worked by then, he said,"We'll just have to see what any third plan looks like, and the cost involved.''

Late in life, Dunlap has been forced to learn to type, work a computer, navigate with a cane, count the steps and memorize the turns from one spot to another, communicate with Siri, and smile as blood-sucking leeches dangle from his cheeks.

Asked about his sources of inner-strength, he responded, "I don't know I'd call it inner-strength.

"I can tell you I certainly believe in the Lord. We pray daily. I appreciate the prayers of others. I think it certainly is a faithissue.''

He also credits his late mother, Cora, a single parentwho managed a grocery. "She was a very optimistic, loving person,'' he recalled.

"And I've had Marcia's support. Marcia wasn't going to let me give up, just sit down and do nothing.''

The Dunlaps are starting to consider resuming their annual trips to Cubs spring training in Arizona. Maybe next spring.

"You may have your vision by then,'' Marcia told John.

"I might,'' he responded."We'll see.''

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Will putting leeches on his face help this blind man see? - USA TODAY

HACKENSACK, N.J. and PETACH TIKVAH, Israel, Aug. 7, 2017 /PRNewswire/ --BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of adult stem cell technologies for neurodegenerative diseases, announced today the appointment of Mary Kay Turner to the position of Vice President of Patient Advocacy and Government Affairs, effective August 7, 2017. Ms. Turner joins BrainStorm from Mitsubishi Tanabe Pharma America, where she was Head of Patient Advocacy and Communications supporting the commercialization of edaravone (Radicava) for amyotrophic lateral sclerosis (ALS). Her prior industry experience includes senior sales leadership roles and she was Head of State Government Affairs and Advocacy for Bristol-Myers Squibb Company.

"We are pleased to have Mary Kay join our company as we advance our ALS clinical program and prepare to initiate Phase 3 testing of NurOwn," said Chaim Lebovits, President and Chief Executive Officer of BrainStorm Cell Therapeutics. "Having a strong patient advocacy perspective and voice in the community is integral to our mission of advancing tomorrow's medicines. Mary Kay brings an extensive background in patient advocacy, government affairs and health policy. We are fortunate to have someone with her biopharma expertise and dedication to the patient community join our team."

"Mary Kay will lead the development and implementation of external collaborations that will address and support the needs of people living with ALS", said Dr. Ralph Z. Kern, MD, MHSc, Chief Operating Officer and Chief Medical Officer of BrainStorm. "Working directly with patient advocacy groups deepens our understanding of patients' needs and aligns our efforts with the broader ALS community."

"I have been impressed by the progress BrainStorm has made with NurOwn, particularly the outstanding Phase 2 clinical data which showed meaningful improvements in disease symptoms," said Mary Kay Turner. "Joining the company at this exciting juncture provides a great opportunity to work with respected leaders in neurology and cell therapy and to contribute to the development of a new treatment that could potentially transform the ALS landscape."

Mary Kay is recognized as a leader within the biopharma industry for developing advocacy and government affairs strategies. Most recently she worked at Mitsubishi Tanabe Pharma America as Head of Patient Advocacy and Communications. Prior to this, Mary Kay spent 26 years at Bristol Myers Squibb Company where she played an essential role in establishing the company's advocacy function and held various positions of increasing responsibility in sales leadership, patient advocacy and government affairs. From 2010 to 2016, she was Head of State Government Affairs and Advocacy at Bristol-Myers. In this role she led a team of government affairs professionals that focused on significant legislative and regulatory issues that promoted and protected the discovery and development of innovative therapies. Mary Kay helped to define the company's advocacy strategy and engagement for each of its key therapeutic areas.

In 2016, Mary Kay was appointed to the Arizona Biomedical Research Commission by Arizona Governor Doug Ducey and served a one-year term.She was on the Board of Advisers for the International Cancer Advocacy Network (ICAN).Currently, Mary Kay is a member of the Board of Directors for the ALS Hope Foundation. She also served on the Board of Directors for Mental Health America for 3 years. Mary Kay has a Bachelor of Arts degree in Political Science and History from the University of Oregon.

About BrainStorm Cell Therapeutics Inc.

BrainStorm Cell Therapeutics Inc. is a biotechnology company engaged in the development of first-of-its-kind adult stem cell therapies derived from autologous bone marrow cells for the treatment of neurodegenerative diseases. The Company holds the rights to develop and commercialize its NurOwn technology through an exclusive, worldwide licensing agreement with Ramot, the technology transfer company of Tel Aviv University. NurOwn has been administered to approximately 75 patients with ALS in clinical trials conducted in the United States and Israel. In a randomized, double-blind, placebo-controlled clinical trial conducted in the U. S., a clinically meaningful benefit was demonstrated by higher response to NurOwn compared with placebo. For more information, visit the company's website at http://www.brainstorm-cell.com.

Radicava is a registered trademark of Mitsubishi Tanabe Pharma America.

ContactsMedia:Uri YablonkaChief Business OfficerBrainStorm Cell Therapeutics Inc.Phone: 646-666-3188rel="nofollow">uri@brainstorm-cell.com

Investors:Michael RiceLifeSci Advisors, LLCPhone: 646-597-6979rel="nofollow">mrice@lifesciadvisors.com

View original content with multimedia:http://www.prnewswire.com/news-releases/brainstorm-supports-commitment-to-als-patient-community-with-appointment-of-a-vice-president-of-patient-advocacy-and-government-affairs-300499934.html

SOURCE BrainStorm Cell Therapeutics Inc.

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BrainStorm Supports Commitment to ALS Patient Community with ... - Markets Insider

THURSDAY, Aug. 3, 2017 (HealthDay News) -- Scientists have created genetically altered skin cells that may control type 2 diabetes in lab mice. And they believe the general concept could someday be used to treat various diseases.

Using a combination of stem cells and "gene editing," the researchers created patches of skin cells that were able to release a hormone called GLP1 in a controlled manner.

The hormone, which is normally produced in the digestive tract, spurs the production of insulin -- the body's key regulator of blood sugar levels.

The scientists found that transplanting the engineered skin patches onto diabetic lab mice helped regulate their blood sugar levels over four months.

Xiaoyang Wu, a stem cell biologist at the University of Chicago, led the "proof of concept" study. He said it raises the possibility that "therapeutic skin grafts" could be used to treat a range of diseases -- from hemophilia to drug dependence.

Wu's team focused on type 2 diabetes in these initial experiments because it's a common condition.

However, a researcher not involved in the study doubted the usefulness of the approach for diabetes specifically.

People with type 2 diabetes already manage the disease with diet, exercise and medications -- including ones that target GLP1, said Juan Dominguez-Bendala.

Using high-tech gene therapy to get the same result seems unlikely, said Dominguez-Bendala, an associate professor at the University of Miami's Diabetes Research Institute.

"I don't see something like this coming to the clinic for diabetes," he said.

But Dominguez-Bendala also pointed to what's "cool" about the experiments.

Wu's team used a recently developed technology called CRISPR (pronounced "crisper") to create the skin patches. The technique, heralded as a major breakthrough in genetic engineering, allows scientists to make precision "edits" in DNA -- such as clipping a particular defect or inserting a gene at a specific location.

Before CRISPR, scientists could not control where an inserted gene would be integrated into the genome. It might end up in a "bad" location, Dominguez-Bendala explained, where it could, for example, "awaken" a tumor-promoting gene.

Wu and colleauges used CRISPR to make specific edits in GLP1, including one that allowed the gene to be turned "on" or "off" as needed, by using the antibiotic doxycycline.

The modified gene was inserted into mouse stem cells, which were then cultured into skin grafts in the lab. Finally, those grafts were transplanted onto lab mice.

The researchers found that when the mice were fed food with tiny amounts of doxycycline, the transplanted skin released GLP1 into the bloodstream. In turn, the animals' insulin levels rose and their blood sugar dipped.

The engineered skin also seemed to protect the mice from the ravages of a high-fat diet. When the mice were fed a fat-laden diet, along with doxycycline, they gained less weight versus normal mice given the same diet. They also showed less resistance to the effects of insulin, and lower blood sugar levels.

According to Wu, the study lays the groundwork for more research into using skin cells as a way to deliver "therapeutic proteins."

For instance, he said, skin cells could be engineered to provide an essential protein that is missing because of a genetic defect. As an example, he cited hemophilia -- a genetic disorder in which people lack a protein that allows the blood to clot properly.

Skin cells could be an ideal way to deliver such therapies, Wu said.

For one, the safety of skin grafts in humans is well-established, he pointed out. Since the 1970s, doctors have known how to harvest skin stem cells from burn victims, then use those cells to create lab-grown skin tissue.

Because the skin is generated from a patient's own stem cells, that minimizes the issue of an immune system attack on the tissue.

Dominguez-Bendala agreed that using skin cells has advantages. For one, he noted, the skin graft can be easily removed if something goes awry.

But a lot of work remains before therapeutic skin grafts could become a reality for any human disease. And research in animals doesn't always pan out in humans.

A next step, Wu said, is to see whether the skin grafts maintain their effects in lab mice over a longer period. The researchers will also monitor the animals for any immune system reactions against the GLP1 protein itself.

The findings were published online Aug. 3 in Cell Stem Cell.

The U.S. National Institutes of Health has a primer on gene therapy.

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Engineered Skin Cells Control Type 2 Diabetes in Mice: Study ... - Arizona Daily Star

Arizona researchers, educators, students and representatives of industry, government agencies and health care institutions gathered at the annual ASU Molecular, Cellular and Tissue Bioengineering Symposium in 2016 and 2017 to discuss the potential these fields hold for sparking medical advances. Photo by: Marco-Alexia Chaira/ASU Download Full Image

The main thrust of biomedical engineering has long involved the hardware that the field produces devices, tools, machines, electronics and prosthetic apparatuses.

Now the spotlight is rapidly being shared by engineers and scientists who are seeking to solve medical challenges through their increasing ability to manipulate cells, molecules, genes, proteins and neural systems those so-called soft, pliant and sometimes living biomaterials.

So, about four years ago, it really started to make sense to form a group to strategize about how we could grow this area at ASU, both in the labs and the classrooms, said Haynes, a synthetic biologist and assistant professor of biomedical engineering in ASUs Ira A. Fulton Schools of Engineering.

We needed to start connecting with each other, to share knowledge and to collaborate to bring these new things happening in the biomedical field to the forefront here, said Rege, a professor of chemical engineering in the Fulton Schools.

The Molecular, Cellular and Tissue Bioengineering Group made its public debut of sorts with the inaugural Molecular, Cellular and Tissue Bioengineering Symposium at ASU in 2016, followed by a second symposium last spring that drew almost 150 participants, nearly doubling attendance at the first event.

The gatherings included not only university faculty and graduate students from across Arizona but also representatives from industry and state health agencies.

Audiences saw presentations and heard talks about an expanding array of biomedical techniques being developed that hold promise for treating diseases, healing damaged organs and alleviating various disorders.

There are therapeutic gene editing and DNA sequencing techniques being developed with the aim of curing disease.

Researchers are exploring the use of certain proteins produced by our bodies to treat diseases proteins that could potentially be more effective than the chemical compounds in the drugs that are now widely used.

With our ability to figure out how DNA is expressed and translated into a protein, we now have a much clearer picture of all the different types of coding sequences in DNA and the proteins that are produced by the body, Haynes explained.

Assistant Professor Karmella Haynes (right) says a stronger emphasis on educating students about the biological side of biomedical engineering can broaden their skills and boost their career prospects. Photo by: Jessica Hochreiter/ASU

That capability, she said, enables us to take a healthy cell and compare it to a diseased cell, and then say This is what is right in the healthy cell and these are the things that are wrong in the unhealthy cell. Then we could introduce the right things into the diseased area to try to fix it.

Reges research team is investigating other aspects of such regenerative medicine.

One project involves experimentation with efficiently delivering therapeutic molecules into cells that could target areas of disease.

Techniques like that could also be part of new processes to perform body tissue repair, helping to seal internal organs after surgical incisions in conjunction with the use of laser light to activate sealing and even healing organ tissues damaged by injury or disease.

Other Fulton Schools faculty members are doing work that demonstrates the myriad possibilities of applying new bioengineering skills to improve human health.

Assistant Professor Jeffrey La Belles team is developing implantable and wearable point-of-care sensing systems for disease diagnosis and management.

The technologies utilize molecular recognition of such things as enzymes, antibodies and DNA for sensing particular molecular targets that provide information about certain health conditions.

By sensing multiple biomarkers, the devices can help medical professionals better determine proper care by more accurately assessing patients conditions, La Belle said. They can be particularly effective in enabling people with diabetes, cardiovascular disease and abdominal organ transplants to monitor their health, and for improving evaluation of the status of trauma patients.

Associate Professor Xiao Wang is involved in the design and construction of gene circuits. That entails deeper understanding of the bodys complex gene-regulation networks and what triggers the cell differentiation process, by which stem cells transform into a range of specialized cells critical to the functioning of essential bodily systems.

The aim is to find ways to more effectively determine cell fate, Wang said. Controlling those transitions would make it possible to produce cells designed to help treat infections and diseases, and repair tissues and organs.

Achieving that could help reduce the need for transplants and improve therapies and treatments for spinal injuries and perhaps even Alzheimers Disease and blindness.

Associate Professor Sarah Stabenfeldt is focusing on new and improved therapeutics and diagnostics for brain injury, employing techniques springing from discoveries in molecular biology, neuroscience and materials science to develop and evaluate those diagnostic and treatment systems.

She is experimenting with the use of engineered nanobodies therapeutic proteins derived from antibodies that contain structural and functional properties of naturally occurring antibodies.

The goal is to develop nanoparticle systems that can be introduced into the bloodstream as targeting probes that locate the molecular and cellular source of brain damage.

Those tiny probes would be able to recognize the complexity and severity of neural injury to the brain at the molecular level, thus providing more relevant information to guide treatment of traumatic brain injury, Stabenfeldt said.

Assistant Professor Rachael Sirianni is employing similar approaches to develop more effective treatments for cancer and other degenerative diseases.

Sirianni is an adjunct biomedical engineering faculty member with the Fulton Schools whose primary appointment is with the Barrow Neurological Institute at St. Josephs Hospital and Medical Center in Phoenix, where she runs an academic research program that includes joint ASU/BNI neuroscience endeavors.

She is exploring the use of biomaterials for targeted drug delivery. tissue engineering and medical imaging. Shes confident that work in in these and related areas will eventually help bring about significant medical advances.

The range of problems we can tackle and the knowledge we can gain through these emerging aspects of bioengineering will eventually lead to better therapeutics and a big overall impact on the future of clinical care, she said.

Professor Kaushal Rege (second from left) says the Molecular, Cellular and Technology Group will work to earn more support for research training programs for graduate and postdoctoral students. Photo by: Nora Skrodenis/ASU

There are obstacles that must be overcome to achieve the scientific and engineering capabilities necessary to fulfill that promise, she added, but she believes collaborations like those being fostered by the Molecular, Cellular and Tissue Bioengineering Group could speed progress.

Along with about a half dozen other Fulton Schools faculty, colleagues in ASUs School of Life Sciences, the School of Molecular Sciences and research specialists with the Biodesign Institute are also engaged in advancing knowledge in molecular, cell and tissue biology.

Much of that work has drawn support from the likes of the National Science Foundation, the National Institutes of Health, the ASU Foundations Women & Philanthropy program, the American Heart Association and the Arizona Biomedical Research Commission, which also provided $20,000 to help fund this years ASU Molecular, Cellular and Tissue Bioengineering Symposium.

The ABRC, a part of the Arizona Department of Health Services, sees significant benefits for the state in helping to create a shared sense of community among engineers, scientists, industries and healthcare institutions interested in making medical advances, said Jennifer Botsford, the commissions program manager.

The faculty group has the potential to create opportunities for cross-fertilization of ideas that push the boundaries of science, said Betsy Cantwell,vice president of research for ASUs Knowledge Enterprise Development office

Their work is not only necessary, but genuinely innovative and inclusive, as demonstrated by their national stature and international connections, Cantwell said.

Such endorsements are motivating the group to put plans into action to more solidly establish its identity and pursue its long-range goals.

Haynes is hoping that by next year the symposium will start to become more of a regional event and draw prominent experts and industry leaders from throughout the Southwest.

She and Rege also hope to encourage more serious discussion with ASU leaders about ideas for a future lab complex or even a building where the universitys biomedical researchers could be headquartered.

To optimize our resources and make full use of our talents, its important to have an environment that allows us to see and talk to each other about our individual work, Rege said. That is how ideas get generated and collaborations happen.

On one front, the groups aspirations are already taking shape.

The Fulton Schools biomedical engineering program is in the process of launching a new curriculum track that will make this soft, squishy side of the field more of an educational focal point at ASU.

This is a huge deal, Haynes said, because we can offer more to students who want a stronger combination of medical education and engineering thats going to open up their career possibilities.

The group seeks to not only attract more funding for faculty research but also for research training programs for graduate students and postdoctoral students.

That would be a significant step toward elevating ASU among medical science and engineering education leaders.

Said Rege: We want this to be a place where people can come to see and learn about and contribute to really big things happening in all these fields. Thats our vision.

Go here to read the rest:
'Soft' side of bioengineering poised to make big impacts - Arizona State University

June 21, 2017

Improving the quality and quantity of research into cancers with the poorest survival rates remains a key priority across all aspects of our research activity from funding breakthroughs in biology, to growing a sustainable community of world-leading researchers.

In the three years since we pledged to increase research funding in cancers of unmet need, we have increased spend in our four identified priority cancers lung, pancreatic, oesophageal and brain. We invested 85.8m across these four disease types in 2016/17, more than doubling our spend since 2013/14.

But our ambitions in tackling these hard-to-treat diseases go far beyond funding research, as each of these intractable diseases has its own unique challenges.

We have been working closely with the community to determine the critical scientific questions or identify gaps in infrastructure standing in the way of progress, with a view to taking proactive, bespoke approaches to each disease type. Activities have ranged from specialist symposia and conferences bringing the research community in these fields together, to looking at ways to fund large-scale international research initiatives in partnership with others. A second symposium on oesophageal cancer took place in spring 2017, followed by a workshop with key members of the international research community to identify priority areas for research. And with the long-term view of building a sustainable community working on each disease, it is encouraging that this year we have seen an increase in the number of career development awards focused on the unmet need cancers, particularly in brain tumours.

In lung cancer, a notable highlight this year is a collaboration through our partnership with the US Cancer Moonshot Initiative which will see Professor Caroline Dive at our Manchester Institute and Professor Peter Kuhn's team at the University of Southern California apply their combined expertise and technology in circulating tumour cell analysis to study the blood of patients with early-stage lung (and bowel) cancer, to see if they can identify those who will relapse.

Here, we focus on two of the toughest cancers pancreatic and brain and share some of the exciting investments, initiatives and new research we're funding in the UK and internationally.

Tackling pancreatic cancer

Every year around 9,500 people are diagnosed with pancreatic cancer in the UK; only 1% survive their disease for 10 years or more. Surgery can significantly extend overall survival, but only 1015% of patients are diagnosed early enough for surgery to even be an option. Other treatments only prolong life by a matter of months. Now the 11th most common cancer in the UK, new approaches are urgently needed to combat this devastating disease.

A new era of precision

As for all cancers, molecular stratification of tumours is key to our basic understanding of pancreatic ductal adenocarcinoma (PDAC), and its prognosis and treatment. Professor Andrew Biankin, at the University of Glasgow, is a leader in molecular analysis and next generation sequencing of pancreatic cancers: besides confirming known mutations, his work has uncovered new genes and pathways mutated at lower frequencies, some of which are potential therapeutic targets. He is lead investigator on PRECISION-Panc, an ambitious programme of research that seeks to uncover the molecular profile of individual patients with pancreatic cancer, to learn more about the disease and to facilitate patients entering clinical trials for treatments that match their tumour biology. CRUK is investing 10m in this flagship initiative, to date our largest stand-alone investment in pancreatic cancer research. He also co-chairs Precision Promise, a sister programme to PRECISION-Panc, that will bring precision medicine to pancreatic cancer patients in the US.

Andrew's aim is to pull together a knowledge bank about PDAC, taking in information not just from the US and the UK, but from many other partners around the world. His hope is that, eventually, a newly-diagnosed patient's tumour characteristics can be run against the knowledge bank database, enabling the best treatment option to be offered as part of a clinical trial: "There'll be a day in the future, if we harmonise and align our methodology, that we can address specific issues through running international multicentre studies", he says, "but for that, we'll have to better integrate research with the clinic. We want a patient to know when experimental medicine is the best option for them, and make sure that they have trials to enter."

Targeting the molecular basis of pancreatic cancer

From the work of Andrew and others, we know that the KRAS oncogene is mutated in 80100% of PDACs, and has a frequent partner in crime: the MYC oncogene. Amplification of MYC in PDAC makes the tumours more aggressive, and, as in many other tumour types, MYC expression is critical for KRAS-driven tumour maintenance. Recently, it's been shown that MYC regulates so-called super-enhancers clusters of DNAprotein complexes that coordinate the expression of large banks of genes critical for specifying cell identity and behaviour. This may be how MYC can reprogramme cells at the flick of a switch. Because of its importance, MYC is one of the lead molecules being studied by the Pancreatic Cancer Dream Team, funded through a partnership between CRUK, Stand Up To Cancer (SU2C) and the US Lustgarten Foundation.

Led by Professor Gerard Evan at the University of Cambridge, Professor Daniel von Hoff at the Translational Genomics Research Institute in Arizona and Professor Ronald Evans at the Salk Institute for Biological Sciences in California, the Pancreatic Cancer Dream Team aims to map super-enhancer 'hotspots' in pancreatic cancers. They hope to understand how MYC 'hacks' into the normal regenerative programme of the pancreas, driving relentless proliferation and, eventually, pancreatic cancer. In particular, they are studying how MYC engages with the super-enhancers in pancreas cancer cells and how disabling that interaction triggers regression of pancreatic cancers. This knowledge will inform the use of super-enhancer-targeted drugs, some of which are already available, and has the potential to enhance responses to chemo- and immunotherapy.

One year in, Gerard has found the collaboration immensely rewarding: "The notion of looking at transcriptional changes would probably not have been something we'd have gone for in our own lab, as we didn't have the necessary expertise," he says, "so this was, and is, a game-changing opportunity for us and, we hope, for pancreatic cancer patients."

Targeting the microenvironment

One of the hallmarks of PDAC is extensive desmoplasia the formation of rigid fibrotic tissue or extracellular matrix, wrapped like a corset around the tumour. In some PDACs, as much as 90% of the tumour mass comprises non-tumour cells, and this stromal tissue shapes the tumour, both literally and metaphorically, toughening it up by starving it of oxygen and nutrients, and impeding treatment by reducing the access of drugs and immune cells.

These stromal and tumour cells talk extensively to each other. Dr Claus Jrgensen, at the CRUK Manchester Institute, made the crucial discovery last year that oncogenic KRAS ramps up tumour cell signalling by coercing the stroma into feeding paracrine signals back to the tumour. And this communication extends into 'mechanotransduction' too where cells sense their rigidity and that of their surroundings and convert that information into signals that control behaviours such as proliferation and invasion.

Building on this, Claus has set up a collaboration with Professor Martin Humphries at the University of Manchester, who has made fundamental discoveries about the basic mechanisms of cell adhesion, to determine how stromal rigidity drives proliferation. "Adhesion has evolved over hundreds of millions of years to control cell fate it's not simply a way of sticking cells together," says Martin. They will be studying how the adhesion nexus a cluster of receptors, extracellular matrix fibres and cytoskeletal polymers works as a sensor of stromal rigidity in PDAC, and hope to unpick exactly how desmoplasia forces proliferation under unfavourable circumstances, thereby accelerating tumour progression.

Tackling brain cancers

CRUK's spend on brain tumour research has more than doubled in the last five years. But growth since the launch of the Research Strategy in 2014 has been modest, suggesting more needs to be done. Brain cancer remains a challenging area in which there is limited research activity. To address this we held an international workshop in 2016 with a panel of expert leaders in the field. The meeting identified key research areas seen as crucial for the progress of brain tumour research and improving patient outcomes. We are now looking at ways to highlight these questions to the research community and to fund research to address them.

Like pancreatic cancer, glioblastoma, the most aggressive form of brain cancer, is intractable and rapidly lethal. Though thankfully rare, with around 2,300 cases in England each year, survival is low with less than 5% surviving for at least five years.

Clinician scientist Dr Paul Brennan, a recent Pioneer Award recipient, works on the frontline of glioblastoma, combining his work as a consultant neurosurgeon at Edinburgh's Western General Hospital with research at the CRUK Edinburgh Centre. When it comes to brain cancer, being a surgeon is peculiarly frustrating: "This is a disease that can't be cured surgically. In the brain, there's no natural containment barrier; glioblastomas spread quickly along the normal white matter tracts, so removing the mass isn't curative," he explains. "Eventually I'd hope only to offer surgery to people with no alternative. Frustratingly, at the moment, that's everyone."

Paul's Pioneer Award relies on a collaboration with two colleagues at the CRUK Edinburgh Centre Dr Dirk Sieger, who models brain cancer in zebrafish, and Dr Asier Unciti-Broceta, a medicinal chemist. Asier's work on palladium catalysts drives the project, and came to Paul's notice during a thesis committee meeting for one of Asier's students: "I remember thinking that although this is a pure chemistry PhD and I don't understand the aromatic chemistry, I do understand how this would be applicable to brain tumours", Paul says.

Glioblastomas tend to recur at their original site, implying that, post-surgery, residual cells remain. The Pioneer Award will be used to study the potential of implanting inert palladium beads at the time of surgery, and then treating patients with a prodrug that the palladium catalyst will activate. "We should be able to give people a higher concentration of the drug and avoid some of the side effects," Paul says. They hope to develop prodrugs that work in Dirk's zebrafish glioma model, providing proof-of-principle evidence needed to scale up the project and take it into pre-clinical development.

Developing research resources

Moving the brain cancer field forward will require the development of communal research resources to mine the knowledge gleaned from patient cell lines and samples, something that Dr Steve Pollard, also at the CRUK Edinburgh Centre, is passionate about. As well as having his own glioblastoma research programme, Steve is the principal investigator for the Glioma Cellular Genetics Resource (GCGR), funded by CRUK in 2016 through an Accelerator Award. The GCGR will be a centralised resource for the generation, cataloguing and curation of glioblastoma cell lines, accessed via an open source database. Genome editing tools and novel engineered patient-derived cellular models will also be on offer Steve's already receiving plenty of requests for the CRISPR tools he's developed in the last year for modifying target genes of interest.

There's a training and recruitment component too: a new generation of scientists will be nurtured via the PhD programme associated with the award, and the participation of the developmental neurobiologists at the Francis Crick Institute is a route for bringing some excellent basic scientists into the glioblastoma field: "We hope to tempt them in with the unique resources we can offer," he says, "Our cell lines, for example, contain a whole spectrum of glioblastoma mutations, many of which may have profound implications for normal neural development."

Taking a global view

International cooperation is vital for rare cancers, where national patient numbers are frequently too low to permit meaningful studies, and this is especially so in the challenging field of paediatric brain tumours. Professor Richard Gilbertson, at our Cambridge Centre, believes that the availability of big data means that the global community can now work together in a more purposeful way: "Next generation sequencing has allowed us to look into the biology of childhood cancer in a way we've never done before," he says. "It's like looking for keys in a dark room. What next generation sequencing has done is switched the light on so you can see the keys. You don't necessarily know what lock the keys fit but at least you've found them."

The tumour transcriptome has meant that paediatric brain cancers are now beginning to be stratified, but Richard says the challenge is to transfer this knowledge into the clinic: "We now know, for example, that in medulloblastoma there are four distinct subgroups, one of which does really well and should probably be spared radiotherapy. There are things we're armed with now that will make an impact, and I have a lot of hope for the next five years."

Major advances

In his own lab, Richard has had a long-standing preoccupation with the paradox that tissues grow faster during childhood than at any other time, and yet childhood cancers are so rare: "If you have a tissue with this massive mitotic process going on there has to be a mechanism in there to stop it becoming malignant," In what he believes is the most significant work of his career, CRUK-funded work from his lab published last year in Cell showed this to be true: stem cells that give rise to adult cancers are about seven-fold more sensitive to generating cancer than paediatric stem cells.

The results have profound implications: "Because we know precisely what those cells are, we can interrogate them at the molecular level in adults and neonates across all organs to find whether there is a particular biological cassette in a neonatal cell that is protecting it from cancer," Richard says. "And if you could pharmacologically activate that in adults, you'd have a system that was no longer susceptible to cancer."

Major discoveries draw people and resources into a field, and cause a build-up of momentum that pushes the field forward. Up until now, such advances have been few and far between in the cancers identified by CRUK as unmet needs. Now, though, thanks to the influx of new blood synergising with the expertise and dedication of long-term researchers, those discoveries are starting to come; and as some of the work profiled here shows, the consequences may be profound, not just for single cancers, but for the whole spectrum of disease.

Explore further: Improving radiotherapy for brain cancers

Journal reference: Cell

Provided by: Cancer Research UK

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For several months I had noticed tremors in my right hand and the shaking of my right foot when I was sitting. My normally beautiful cursive writing was now small cramped printing. And I tended to lose my balance. Neurologist had me walk down the hall and said I didn't swing my right arm. I had never noticed! I was in denial for a while as there is no history in my family of parents and five older siblings, but now accept I had classic symptoms. I was taking pramipexole (Sifrol), carbidopa/levodopa and Biperiden, 2 mg. and started physical therapy to strengthen muscles. nothing was really working to help my condition.I went off the Siferol (with the doctor's knowledge) and started on parkinson's herbal formula i ordered from Health Herbal Clinic, my symptoms totally declined over a 5 weeks use of the Parkinsons disease natural herbal formula. i am now almost 70 and doing very well, the disease is totally reversed!! Visit there website www. healthherbalclinic. net

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Tackling hard-to-treat cancers from every angle - Medical Xpress

Testing stem cell therapies unilaterally?A side-by-side comparison of strength of key muscles may enable scientists to evaluate stem cell therapies for the disease. The approach aims to control for the variability of the disease internally, without historical cohorts and/or the use of a placebo (see Donofrio and Bedlack, 2011; Glass et al., 2016).The biceps and triceps appear to be most reliable muscles to monitor progression in people with ALS according to this analysis (Rushton et al., 2017). [Neural progenitor cells. Courtesy of Nature Cell Biology. Reproduced with permission.]

Motor neurons degenerate in ALS. Why these cells are destroyed remains unclear. Therefore, how to slow or stop this destruction of motor neurons in ALS remains an open question.

In the meantime, a growing number of scientists are turning to stem cells in hopes to promote motor neuron survival in people with ALS and/or reduce their toxicity (see December 2015 conference news). But how to evaluate these strategies in the clinic remains hotly debated.

Now, a research team at Cedar Sinai Medical Center in Los Angeles, California reports that an emerging outcome measure, which involves monitoring muscle strength, may facilitate the evaluation of stem cell therapies for the disease (Rushton et al., 2017). The study, led by Clive Svendsen, found that functional decline of key muscles on the left and right side of people with ALS progressed at a similar rate. The results suggest that at least some stem cell therapies could be evaluated unilaterally by comparing the strength of muscles on the treated and untreated side for each of these muscle groups.

This side-by-side comparison, according to a subsequent power analysis, may enable clinicians to evaluate stem cell therapies for ALS in a smaller sample size without the need for sham surgeries and/or placebo injections.

This unilateral approach is emerging as an alternative to evaluate a growing number of potential neuroprotective strategies for neurodegenerative diseases including ALS (see NCT02943850, NCT02478450; Glass et al., 2016).

The study is published on June 9 in Neurology.

The retrospective analysis, performed in collaboration with Cedar Sinais Robert Baloh, studied the rates of decline of 6 upper and lower muscle groups in nearly 750 people with ALS determined by fixed dynamometry. These longitudinal datasets, previously collected by physical therapist Pat Andres and colleagues, now at Massachusetts General Hospital, capture the decline in strength of key muscles in people with ALS during at least a 16-month period measured by either the TUFTS Quantitative Neuromuscular Exam (TQNE) or more recently, the Accurate Test of Limb Isometric Strength (ATLIS) system (Andres et al., 1986; Shields et al., 1998; Andres et al., 2012.

Analyzing therapies by hand. Meanwhile, Biogen scientists in Cambridge, Massachusetts are turning to hand-held dynamometry to evaluate potential therapies for ALS. The emerging strength-based measure highly correlates with the progressive loss of motor function (ALS-FRS-R) and breathing capacity (FVC) according to a retrospective analysis of 924 people with ALS presented at the 2017 meeting of the American Academy of Neurology (see May 2017 news). And, according to a subsequent side-by-side comparison, these musclesdecline at similar rates. [Image: Douma et al., 2014 under CC BY 2.0 license.]

The study builds on previous work, led by Barrow Institutes Jeremy Shefner in Phoenix, Arizona and Biogens Toby Ferguson in Cambridge, Massachusetts, which found that monitoring the strength of key muscles using hand-held dynamometry is a reliable and reproducible approach to measure progression of ALS in a clinical setting and thereby, may facilitate the evaluation of potential therapies (see May 2017 conference news; Shefner et al., 2014).

Now, Svendsens team is gearing up to evaluate their potential stem cell therapy for ALS. The strategy uses genetically engineered neural progenitor cells (NPCs) to deliver GDNF into the CNS in hopes to protect motor neurons in people with the disease (see April 2017 news; Gowing et al., 2014). The approach is at the phase 1 stage. Stay tuned.

Featured Paper

RushtonDJ, Andres PL, Allred P, Baloh RH,SvendsenCN. Patients with ALS show highly correlated progression rates in left and right limb muscles. Neurology. 2017 Jun 9. [PubMed].

References

ShefnerJM, Liu D, Leitner ML, Schoenfeld D, Johns DR, Ferguson T, Cudkowicz M.Quantitativestrengthtesting in ALS clinical trials. Neurology. 2016 Aug 9;87(6):617-24. [PubMed].

Andres PL, Skerry LM, Munsat TL, Thornell BJ, Szymonifka J, Schoenfeld DA, Cudkowicz ME. Validation of a new strength measurement device for amyotrophic lateral sclerosis clinical trials. Muscle Nerve. 2012 Jan;45(1):81-5. [PubMed].

Andres PL, Hedlund W, Finison L, Conlon T, Felmus M, Munsat TL.Quantitative motor assessment in amyotrophic lateral sclerosis. Neurology. 1986 Jul;36(7):937-41.[PubMed].

Glass JD, Hertzberg VS, Boulis NM, Riley J, Federici T, Polak M, Bordeau J, Fournier C, Johe K, Hazel T, Cudkowicz M, Atassi N, Borges LF, Rutkove SB, Duell J, Patil PG, Goutman SA, Feldman EL. Transplantation of spinal cord-derived neural stem cells forALS: Analysis of phase 1 and 2 trials. Neurology. 2016 Jul 26;87(4):392-400.[PubMed].

Gowing G, Shelley B, Staggenborg K, Hurley A, Avalos P, Victoroff J, Latter J, Garcia L, Svendsen CN. Glial cell line-derived neurotrophic factor-secreting human neural progenitors show long-term survival, maturation into astrocytes, and no tumor formation following transplantation into the spinal cord of immunocompromised rats. Neuroreport.2014 Apr 16;25(6):367-72. [PubMed].

Further Reading

Atassi N, Beghi E, Blanquer M, Boulis NM, Cantello R, Caponnetto C, Chi A, Dunnett SB, Feldman EL, Vescovi A1, Mazzini L; attendees of the International Workshop on Progress in Stem Cells Research for ALS/MND. Intraspinal stem cell transplantation for amyotrophic lateral sclerosis: Ready for efficacy clinical trials? Cytotherapy.2016 Dec;18(12):1471-1475. [PubMed].

Donofrio PD, Bedlack R. Historical controls in ALS trials: a high seas rescue? Neurology. 2011 Sep 6;77(10):936-7. [PubMed].

clinical trial clinical trial design disease-als gdnf neuralstem neuroprotection stem cell topic-clinical topic-randd

Excerpt from:
ALS Research Forum | To Evaluate Stem Cell Therapies, Think ... - ALS Research Forum

June 13, 2017

Evolution is a propulsive force, working incessantly to reshape life on earth, from the lowliest single-celled organisms to the planets vast forests, insect and bird populations, oceanic life and diverse mammalian species.

Like all living things, cancer cells are also subject to the stringent dictates of evolution. Indeed, cancer has proven to be among the most adept players in natures ceaseless game. Evolution is the reason humans and other life forms are vulnerable to cancer and why the disease has been so challenging to cure. Carlo Maley's research focuses on evolution and cancer biology. He is a researcher in the Biodesign Center for Personalized Diagnostics and an associate professor in the School of Life Sciences at ASU. Download Full Image

In a new book, "Frontiers in Cancer Research: Evolutionary Foundations, Revolutionary Directions," (Springer, 2017), Carlo Maley, a researcher at Arizona State University's Biodesign Institute, illuminates some of the central issues in current cancer study, from the vantage point of evolutionary and ecological theory. The book features chapters written by a range of researchers at the vanguard of the field. Their aim is to highlight some of the most intriguing unanswered questions in cancer research and to propose evolution-based strategies for addressing them.

Ignoring evolutionary transformation cancers primary weapon of destruction has limited progress toward the successful treatment and possible prevention of cancer. By the same token, the authors argue, the rules of evolution, if properly understood and applied, may help science to outwit cancer, either driving it to extinction or curtailing its lethality.

The book begins with a call to arms in the fight against cancer: Nearly everyone working on cancer biology is actually working on evolutionary biology, even if they do not realize it, Maley said. Unfortunately, we suffer from a paucity of evolutionary biologists and ecologists who are studying cancer. The following chapters deliver a rallying cry for other innovative researchers to enter the field and contribute their talents.

Historically, biology has been a largely experimental discipline. Charles Darwin, however, provided a theoretical framework for understanding living systems, a master narrative capable of accounting for the diversity of earthly life, through simple laws. Intriguingly, the twin forces of chance mutation and natural selection also provide cancer cells with their tenacious ability to carve out a hospitable niche, compete for resources and expand their reign at the expense of their host.

The wide-ranging text covers the genetics of cancer populations, genetic diversity within tumors (intra-tumor heterogeneity), the expansion of mutant clones, cancer stem cells in the dynamics of tumors, the evolution of metastasis, and techniques for improving cancer therapy through monitoring cancers evolutionary response to treatment.

Additional chapters address the patterns of human cancer susceptibility due to a mismatch between modern environments and those in which our species evolved, as well as the evolution of cancer suppression mechanisms that have emerged in different species; particularly the large long-lived animals like elephants and whales that are better at suppressing cancers than humans. Perhaps these adaptations can provide new sights relevant for human therapy and cancer prevention.

The topic of cancer heterogeneity is a central theme of the book. The existence of a wide variety of mutant cells usually present in the patient before initial diagnosis presents the most formidable challenge to effective treatment. The authors propose that such diversity is so ubiquitous that it may be applied as a universal biomarker an early warning beacon indicating the propensity for cancer development or the severity of the particular cancer diagnosis. Diversity may therefore provide a common denominator, useful for tracking and characterizing cancers through all their bewildering subtypes.

In addition to disease diagnosis, measures of cancer cell diversity may also help guide the course of therapy. Here, the authors stress a central misconception in conventional cancer treatment one which persists in spite of evolutionary theory. Efforts to eradicate all cancerous cells in a diverse population effectively select for those cells resistant to treatment. Eliminating evolutionary competition between varying cell types allows resistant post-treatment cells to expand without limit, forming a sort of super-charged cancer, less susceptible to management.

The authors trace the history of the current impasse in cancer treatment, attributing it in part to the revolution in molecular biology, which may have unwittingly acted to sideline evolutionary approaches. Clinical methods that met with enormous success in treating viral and bacterial infections have proven largely impotent against the protean nature of cancer, which, unlike a foreign pathogen, is a moving target comprised of the hosts own cells.

As John W. Pepper of the National Cancer Institute writes in the book: ... cancer cells are genetically heterogeneous but fundamentally human, as opposed to infectious cellular diseases that are homogeneous and fundamentally non-human. Clearly, a reevaluation of reductionist tactics will be critical in breaking the treatment stalemate. Magic-bullet approaches to cancer, the authors argue, have dominated clinical thinking but have largely amounted to dead ends.

The dynamic nature of evolution poses particular challenges for cancer research and treatment. Cancers are often diagnosed at a single time point, with one sample per tumor, an approach that masks the subtle evolutionary processes driving cancer progression. A transition to multiple sampling to yield a more representative, time-sensitive picture of tumor evolution is encouraged, though at present, this is often cost- and time-prohibitive.

A popular theory declares that not all cancer cells are created equal. Even cells that are genetically identical may behave differently. In this view, so-called cancer stem cells, which are distinct from neighboring cancer cells in that they are self-restoring, act to drive the progression of the disease, with surrounding cells acting merely as bystanders. From the standpoint of treatment, cancer stem cells are of central concern and a failure to eradicate them will inevitably lead to regrowth of the tumor.

Chapter 8 is devoted to cancers most lethal attribute, its ability to spread from the region of primary malignancy to other areas of the body, a phenomenon known as metastasis. Indeed, most cancer fatalities are the result of metastasis. Here again, research has only scratched the surface in terms of understanding the subtle particulars driving this aspect of cancer. What seems clear is that metastasizing cells often display greater aggressiveness and adaptability compared with their primary tumor counterparts. Thwarting metastasis is therefore among the primary objectives of ongoing research, with evolutionary models paving the way for new insights.

Given the selective pressure exerted by anti-cancer drugs, which cause Darwinian dynamics to select for treatment-resistant cells, what alternatives exist? One of the most exiting clinical innovations resulting from an evolutionary re-thinking of cancer is described by Robert Gatenby, a pioneer in what is known as adaptive therapy.

The basic idea is to maintain cells in the tumor that remain sensitive to the therapy so that they can out-compete resistance cells. The goal is to maintain the tumor at a stable size. So, when the tumor shrinks in response to therapy, the oncologist lowers the dose, but when it grows, she raises the dose. The aim is to stabilize the tumor by insuring active intra-tumor competition, rather than attempt to kill a maximum number of cells via conventional chemotherapy or radiation. The method is likened by Gatenby to the predator-prey arms race often seen in adaptive landscapes of differing species.

How can we deal with the evolutionary resilience of cancer? The sobering conclusion of the book stresses cancers virtually limitless capacity to reemerge in new, resistant guises due to compulsive evolution, a fact that may continue to sabotage our best efforts to shut it down. Prevention and the earliest possible interventions when heterogeneity may still be limited offer the best chances in the near term for beating this implacable illness. Time is the enemy.

Link:
New book by ASU researcher explores cancer's pervasive mysteries - Arizona State University

Glassholic/FoterIn considering the rights of Native American foster children, should the emphasis be placed on their status as Native Americans or as children?

The Arizona Supreme Court chose the latter, clearing a non-native couple to adopt their foster daughter over objections of a local Indian tribe.

The court's ruling is a challenge to the controversial 1978 Indian Child Welfare Act (ICWA). Proponents say the act is essential to keep Native American communities together. Critics contend it establishes a racially discriminatory system that negatively affects the safety and welfare of Indian children.

At the time of ICWA's passage, removal of Native American children from their homes was "truly an epidemic that threatened native American children and their families," David E. Simmons, Government Affairs Director for the National Indian Child Welfare Association, tells Reason.

ICWA sought to stem this so-called epidemic by conferring upon sovereign tribal nations the right to be involved in the adoption process of their citizens. Tribes were free to employ "community-based services and community-based knowledge" in deciding on the placement of children.

ICWA, however, has little do with the legal or cultural attachment of a child to a tribal community, and everything to do with a biological attachment to a racial group, Timothy Sandefur, Vice President for Litigation at the Goldwater Institute, says.

The Goldwater Institute has intervened in a number of ICWA cases including this most recent one in Arizona.

"If you have the right blood cells in your veins, then ICWA applies a separate and substandard set of rules that makes it harder to protect you from abuse and neglect, and harder to find you an adoptive home," Sanderfur says.

In 2014 an infant identified as A.D. in court documents was born to a member of the Gila River Indian Community. Both A.D. and her mother tested positive for amphetamines and opiates and the Arizona Department of Child Services ordered the child placed her current non-native foster parents.

Sarah and Jeremy H., according to the court documents, moved to adopt A.D in Arizona state court in June 2015. But despite repeated failures to find a suitable tribal family for A.D., the Gila River Indian Community blocked the adoption claiming tribal court jurisdiction through ICWA.

The Arizona Supreme Court unanimously rejected the Gila River Indian Community's argument, but broader concerns about the authority of ICWA remain. The act's departure from standard adoption law has exposed Native American children to parents who have systemically physically and sexually abused them, Sandefur says.

Laws that govern foster care for children of all other races, by contrast, require "reasonable efforts" be made to reunite children and parents, but draw the line at trying to return kids to homes where they have experienced "systemic abuse."

One example was the case of Shayla H. Under the ICWA requirement she was returned to a sexually abusive fathera member of the Rosebud Sioux Tribeonly to be removed a month later after further incidences of sexual abuse.

In Minnesota, three siblings were removed and returned to their alcoholic parents so many times child services workers stopped counting at 500.

At the behest of the North Dakota Spirit Lake tribe, Laurynn Whiteshield and her twin sister, were taken from a non-native foster family and placed with her Native American grandfather and a step-grandmother charged eight total with child abuse.

A little more than a month later the step-grandmother was charged with murdering Laurynn Whiteshield.

The most recent Arizona case, Sandefur says, was a narrow victory decided on more technical and procedural grounds. The Goldwater Institute has brought a class action suit in federal court on behalf of off-reservation Indian children subject to ICWA to broaden its impact.

The case is currently before the Ninth Circuit Court of Appeal.

The goal, Sandefur says, is not to strike down the entire law or undermine the authority of Indian tribes.

"It [ICWA] needs to be amended," he says, "with the principle in mind that all Indian children are citizens of the United States entitled to equal protection of the laws, and that means no separate rules based on biology."

More:
Arizona Supreme Court Clears Way For Adoption of American Indian Child by Non-Native Parents - Reason (blog)