April 17, 2017 12:36 ET | Source: Research and Markets

Dublin, April 17, 2017 (GLOBE NEWSWIRE) -- Research and Markets has announced the addition of Jain PharmaBiotech's new report "Drug Delivery in Central Nervous System Diseases - Technologies, Markets and Companies" to their offering.

The delivery of drugs to central nervous system (CNS) is a challenge in the treatment of neurological disorders. Drugs may be administered directly into the CNS or administered systematically (e.g., by intravenous injection) for targeted action in the CNS. The major challenge to CNS drug delivery is the blood-brain barrier (BBB), which limits the access of drugs to the brain substance.

Advances in understanding of the cell biology of the BBB have opened new avenues and possibilities for improved drug delivery to the CNS. Several carrier or transport systems, enzymes, and receptors that control the penetration of molecules have been identified in the BBB endothelium. Receptor-mediated transcytosis can transport peptides and proteins across the BBB. Methods are available to assess the BBB permeability of drugs at the discovery stage to avoid development of drugs that fail to reach their target site of action in the CNS.

Many of the new developments in the treatment of neurological disorders will be biological therapies and these will require innovative methods for delivery. Cell, gene and antisense therapies are not only innovative treatments for CNS disorders but also involve sophisticated delivery methods. RNA interference (RNAi) as a form of antisense therapy is also described.

The role of drug delivery is depicted in the background of various therapies for neurological diseases including drugs in development and the role of special delivery preparations. Pain is included as it is considered to be a neurological disorder. A special chapter is devoted to drug delivery for brain tumors. Cell and gene therapies will play an important role in the treatment of neurological disorders in the future.

The method of delivery of a drug to the CNS has an impact on the drug's commercial potential. The market for CNS drug delivery technologies is directly linked to the CNS drug market. Values are calculated for the total CNS market and the share of drug delivery technologies. Starting with the market values for the year 2016, projections are made to the years 2021 and 2026. The markets values are tabulated according to therapeutic areas, technologies and geographical areas. Unmet needs for further development in CNS drug delivery technologies are identified according to the important methods of delivery of therapeutic substances to the CNS. Finally suggestions are made for strategies to expand CNS delivery markets. Besides development of new products, these include application of innovative methods of delivery to older drugs to improve their action and extend their patent life.

Profiles of 76 companies involved in drug delivery for CNS disorders are presented along with their technologies, products and 99 collaborations. These include pharmaceutical companies that develop CNS drugs and biotechnology companies that provide technologies for drug delivery. A number of cell and gene therapy companies with products in development for CNS disorders are included. References contains over 420 publications that are cited in the report. The report is supplemented with 53 tables and 13 figures.

Key Topics Covered:

Executive Summary

1. Basics of Drug Delivery to the Central Nervous System

2. Blood Brain Barrier

3. Methods of Drug Delivery to the CNS

4. Delivery of Cell, Gene and Antisense Therapies to the CNS

5. Drug Delivery for Treatment of Neurological Disorders

6. Drug delivery for brain tumors

7. Markets for Drug Delivery in CNS Disorders

8. Companies

9. References

For more information about this report visit http://www.researchandmarkets.com/research/qlbkw6/drug_delivery_in

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Zachary Eklum is pictured with Nancy Zimpher, SUNY chancellor, and Cedric Howard, SUNY Fredonia vice president for student affairs.

FREDONIA Three State University at Fredonia seniors, two from Chautauqua County, who collectively have five majors, two minors and GPAs of 3.9 or higher were among 256 SUNY students from across the state to receive the 2017 SUNY Chancellors Award for Student Excellence.

Maria Gordon from Stephentown, Zachary Eklum of Jamestown and Rebecca Hartling of Falconer were chosen from among eight Fredonia finalists.

The awards ceremony and reception for recipients was held on April 5, at the Empire State Plaza Convention Center in Albany.

It is my honor to celebrate the achievements of students who have surpassed SUNYs highest standards of academic excellence and leadership both on and off campus, said Nancy Zimpher, SUNY chancellor.

Every student recognized has demonstrated a strong commitment to his/her degree program, home campus, greater community and much more, Zimpher added.

Maria, Rebecca, and Zachary are excellent examples of the quality of student Fredonia is preparing for success, said Cedric Howard, SUNY Fredonia vice president for student affairs, who attended the awards ceremony. They are not just leaders in and out of the classroom; they are poised to become future leaders in a global society.

The award was created in 1997 to recognize students who have best demonstrated, and have been recognized for, the integration of academic excellence with accomplishments in the areas of leadership, athletics, community service, creative and performing arts, campus involvement or career achievement.

ZACHARY EKLUM

Eklum, who is majoring in biology and has minors in psychology and chemistry, became the first Fredonia student accepted into the Early Assurance Program at Upstate Medical University, which he will enter this fall. He is a son of Todd and Dawn Eklum and was valedictorian of Jamestown High Schools Class of 2013.

Eklum has been an active member in the Biology Club, Health Professions Club, Golden Key International Honour Society and the Fredonia chapter of Beta Beta Beta, the national biological sciences honor society. He has tutored numerous students in chemistry, biology, psychology and physics and is currently engaged in a research project with Psychology Assistant Professor Catherine Creeley that is studying the effects of NICU neurotoxins on the fetus during the third trimester pregnancy using a mouse model. The effects are quantified by comparing the density of cell death (apoptosis) in various regions of the brain across treatment and control groups.

Job shadowing has been a key part of his undergraduate education. Eklum has conducted observations in a primary care physicians office, an operating room and radiology department. His internship at UPMC Chautauqua WCA included emergency, cardiac, orthopedic and general surgical departments, among others.

Eklums capstone internship focused on cardiology and the assessment of implantable cardioverter defibrillators in relation to pre-discharge assessments.

Eklum has been the recipient of numerous honors: Yunghans-Mirabelli Biology Achievement Scholarship, Walter Gotowka Award for Excellence, ACS General Chemistry Award, Golden Key International Honour Society Award, Fiat-Lux Let There Be Light Award and Adele Maytum-Hunter scholarships.

REBECCA HARTLING

Ms. Hartling, who is majoring in molecular genetics and psychology, has served two years as a student researcher with Dr. Nicholas Quintyne, where she has explored the resolution of mitotic defects induced by carcinogen treatment in cancer and non-cancer cells. She has also served as a teaching assistant with Drs. Scott Ferguson, Scott Medler and Quintyne, all of the Department of Biology. She is a daughter of Richard and Renee Hartling and a graduate of Falconer High School.

Hartling will attend Jacobs School of Medicine and Biomedical Sciences at the State University at Buffalo.

Hartling is a member of the Biology Club, Chemistry Club and Pre-Health Professions Club and an undergraduate member of the American Society of Cell Biology. She has given poster presentations of undergrad research at the American Society of Cell Biology annual meeting in San Francisco, the Beta Beta Beta regional convention in Latrobe, Pa., and at Fredonia.

She has served as president and treasurer of Upsilon Chi, the Fredonia chapter of Beta Beta Beta, the national biological sciences honor society, is a member of Psi Chi, the international honor society in psychology, Golden Key International Honour Society and Student Ambassadors Program, and has served as a teaching assistant. The membership ranks in Beta Beta Beta increased dramatically, from seven to 50, during her tenure.

Hartling was accepted into the Fredonia Honors Program as a first-year student, received an Adele Maytum-Hunter Scholarship, Freshman Deans Scholar Award and Fredonia Faculty Staff Scholarship, has served as a mentor in the Biology and Honors programs, was a volunteer in the Relay for Life benefit for the American Cancer Society and participated in Fall Sweep.

Additional campus finalists for the Chancellors Award included: Dean Bavisotto, Emily Bystrak, Madeleine Goc, Connor Hoffman and Mikayla Kozlowski. Also nominated for the award were: Zachary Beaudoin, Jefferson Dedrick, Katelyn Dietz, Bridget Doyle, Joseph Drake, Margaret Fagan, Jonah Farnum, Melissa Goggin, Korrin Harvey, Chelsea Jones, Ilana Lieberman, Chelsea May, Maggie Papia, Charlotte Passero, Ariana Perez, Burgandi Rakoska, John Secunde and Carolyn Sheridan.

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Two County Students Honored With Chancellor's Award - Jamestown Post Journal

Biologists have long known that bacteria grow faster and bigger when the quality of nutrients becomes better, a principle in microbial physiology known as the "growth law," which describes the relationship between the average cell size of bacteria and how fast they grow.

But the growth law has a major hole: It is unable to explain why bacteria divide when they reach a certain critical size, no matter how much or how little nutrients are available.

By applying mathematical models to a large number of experiments in which bacterial growth is inhibited, however, a team of physicists, biologists and bioengineers from UC San Diego discovered the reason for this and in the process developed a "general growth law" that explains the origin of these idiosyncrasies of bacterial physiology.

The researchers detailed their achievements in a paper published in this week's issue of the journal Current Biology.

"A few years ago, we set out to do extensive growth inhibition experiments to test the growth law using the model organism Escherichia coli," said Suckjoon Jun, an assistant professor of physics and molecular biology at UC San Diego, who headed the research effort. "Perhaps not so surprisingly, the original growth law was unable to explain changes in cell size under growth inhibition. Cell size either increased or decreased depending on the inhibition method. Sometimes, cell size did not change at all despite significant growth inhibition."

Jun and his colleagues discovered that when cells began replicating their genetic material in preparation for cell division, cell size remained remarkably constant despite the many genetic processes and changes in the cell such as protein and DNA synthesis, cell wall synthesis and cell shape.

"We realized that this invariant cell size represents a fundamental unit of cellular resources required to start growth and the cell cycle, or the 'engine' of a car, so to speak," said Jun. "This 'unit cell' is the fundamental building block of cell size, and cell size is the sum of all invariant unit cells for any growth condition, explaining the origin of the growth law."

Jun said the development of high-throughput cell sampling techniques and genetic methods such as "CRISPR interference" made it possible for his team to extract large amounts of physiological data from 10 million bacterial cells in their growth inhibition experiments.

"This allowed detailed and reliable statistics, and led to quantitative modeling that made experimentally testable predictions, helping us to understand the data at a deeper level," he added. "This complements the unexpected 'adder' principle that we discovered a few years ago."

Jun said this process was similar to the manner in which the Danish astronomer Tycho Brahe, by collecting better data of planetary orbits, was able to convince the German astronomer Johannes Kepler four centuries ago that planetary orbits, whose origin is gravity, were ellipses and not circles.

"Kepler's elliptical model said nothing about the physical origins of ellipses, but his kinematic modeling was an essential starting point for Newton's work on dynamics 50 years later," Jun said. "We don't know whether biology is following the footsteps of the history of physics, but examples are accumulating that some branches of biology are becoming as quantitative a science as physics."

Story Source:

Materials provided by University of California - San Diego. Original written by Kim McDonald. Note: Content may be edited for style and length.

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Fundamental unit of cell size in bacteria discovered - Science Daily

The University of California, the University of Vienna and Emmanuelle Charpentier (collectively UC) on Wednesday, April 12, filed an appeal to overturn a decision by the Patent Trial and Appeal Board (PTAB) that terminated the interference between a UC patent application for CRISPR-Cas9 gene-editing technology and the patent applications and issued patents of the Broad Institute, Harvard University and the Massachusetts Institute of Technology (collectively, the Broad).

An interference is a legal proceeding to determine who was the first to invent a given technology. Although UCs patent application and the Broads patents and patent application overlap in scope, the February 15 PTAB decision found that the claims in the interference are separately patentable. Accordingly, the PTAB decided to terminate the interference.

The appeal, filed in the U.S. Court of Appeals for the Federal Circuit in Washington, D.C., seeks to have the PTAB reinstate the interference.

Ultimately, we expect to establish definitively that the team led by Jennifer Doudna and Emmanuelle Charpentier was the first to engineer CRISPR-Cas9 for use in all types of environments, including in non-cellular settings and within plant, animal and even human cells, said Edward Penhoet, a special adviser on CRISPR to the UC president and UC Berkeley chancellor. Penhoet is the associate dean of biology at UC Berkeley and a professor emeritus of molecular and cell biology..

Doudna is a UC Berkeley professor of molecular and cell biology and of chemistry and a Howard Hughes Medical Institute investigator. Charpentier is now director of the Max Planck Institute for Infection Biology in Berlin.

Given the revolutionary nature of the CRISPR-Cas9 technology, UC believes that obtaining a timely confirmation that its scientific team was the first to invent the use of the technology in all environments, including eukaryotic cells, is important for current and potential users of the technology, including academia, industry and the public at large.

In parallel, UC intends to pursue continuing applications in the U.S. and globally to obtain patents claiming the CRISPR-Cas9 technology and its application in non-cellular and cellular settings, including eukaryotic cells. Corresponding patents have already been granted to UC in the United Kingdom, and the European Patent Office has announced that it will grant UCs patent on May 10, 2017.

UCs earliest patent application, which describes the CRISPR-Cas9 genome-editing technology and its use in any type of setting, was filed on May 25, 2012, while the Broads earliest patent application was filed more than six months later, on Dec. 12, 2012.

The law firm of Munger, Tolles & Olson LLP will be handling the appeal, with Don Verrilli, former solicitor general of the United States, as lead counsel.

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UC appeals US patent board decision on CRISPR-Cas9 - UC Berkeley

James E. Rothman, newly appointed as a Sterling Professor of Cell Biology, is one of the world's most distinguished biochemists and cell biologists. For his work on how molecular messages are transmitted inside and outside of human cells, he was awarded a Nobel Prize in 2013.

A Sterling Professorship is one of the universitys highest faculty honors.

Rothman helped reveal the mechanism that allows cellular compartments called vesicles to transmit information both in the interior of the cell and to the surrounding environment. The fusion of vesicles and cellular membranes, a process called exocytosis, is basic to life and occurs in organisms as diverse as yeast and humans. Exocytosis underlies physiological functions ranging from the secretion of insulin to the regulation of the brain neurotransmitters responsible for movement, perception, memory, and mood.

Rothmans current research concerns the biophysics of membrane fusion and its regulation in exocytosis; the dynamics of the Golgi apparatus at super-resolution; and the use of bio-inspired design in nanotechnology.

After graduating from Yale College with a degree in physics, Rothman earned a Ph.D. in biological chemistry from Harvard Medical School. He conducted postdoctoral research at the Massachusetts Institute of Technology before moving to the Stanford School of Medicine as an assistant professor. He continued his research at Princeton University, where he became the founding chair of the Department of Cellular Biochemistry and Biophysics at Memorial Sloan-Kettering Cancer Center and vice chair of the Sloan-Kettering Institute. Prior to coming to Yale in 2008, Rothman served on the faculty of Columbia Universitys College of Physicians and Surgeons, where he was a professor in the Department of Physiology and Biophysics, the Clyde and Helen Wu Professor of Chemical Biology, and director of the Columbia Genome Center.

Rothman serves as chair of the Yale School of Medicines Department of Cell Biology and as director of the Nanobiology Institute on Yales West Campus.

He has received numerous awards and honors in recognition of his work on vesicle trafficking and membrane fusion, including the King Faisal International Prize for Science, the Gairdner Foundation International Award, the Lounsbery Award of the National Academy of Sciences, the Heineken Foundation Prize of the Netherlands Academy of Sciences, the Louisa Gross Horwitz Prize of Columbia University, the Lasker Basic Science Award, the Kavli Prize in Neuroscience, the Massry Prize, and the E.B. Wilson Medal. He is a member of the National Academy of Sciences and its Institute of Medicine, and is a fellow of the American Academy of Arts and Sciences.

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James Rothman appointed Sterling Professor of Cell Biology - Yale News

A mouse pancreas imaged withselective plane illumination microscopy, a technique that will be used at EMBL Barcelona.

Ahlgren, Mayer & Swoger/CRG

By Elisabeth PainApr. 11, 2017 , 3:45 PM

BARCELONA, SPAINYou'd have to go back to the years before the economic crisis to feel so much optimism in the Spanish scientific community. In a lecture hall buzzing with excitement, the European Molecular Biology Laboratory (EMBL) and the Spanish government yesterday presented a plan to open a new lab here for the study of tissues and organs. The center, EMBL's first new outpost in 18 years, will host six to eight research groups; a director has yet to be named but recruitment has begun.

The announcement is welcome news to the Spanish scientific community, which has suffered from years of budget cuts and political neglect. The agreement also strengthens Barcelona's profile as one of southern Europe's premier science hubs, adds Joan Guinovart, director of the Institute for Research in Biomedicine here. Barcelona is already one of the hottest spots in biomedicine in Europe," he says.

Headquartered in Heidelberg, Germany, EMBL is an international organization supported by 22 member states; it's not affiliated with the European Union. Over the decades, EMBL has established specialized franchises for structural biology in Hamburg, Germany, and Grenoble, France; for bioinformatics in Hinxton, U.K.; and finally, in 1999, for mouse biology in Monterotondo, Italy. The new branch, housed at the Barcelona Biomedical Research Park (PRBB), will study how cells organize and interact at the tissue level. For a long time, tissue was not possible to study with molecular biology; now it is becoming possible, thanks to the development of new imaging techniques, Jan Ellenberg, the head of EMBL's Cell Biology & Biophysics Unit, said during yesterday's ceremony.

In 2006, EMBL established a joint research unit at PRBB with Barcelona's Centre for Genomic Regulation (CRG), led by current CRG director and former EMBL department head Luis Serrano. The partnership combined computational biology with genomics and proteomics to tackle complex systems biology problems. The quality of the work that was done here was outstanding, EMBL Director-General Iain Mattaj tells ScienceInsider. That helped convince EMBL's other member states to establish a fully fledged lab here, he says, as did the presence of strong universities, research institutes, and a hospital.

EMBL will invest 16 million in the new site during the first 5 years. Spain, which contributes about 9 million annually to EMBL8.5% of the organization's total budgethas put an additional 6 million on the table until 2021. The Catalan government will foot the 400,000 annual bill for rent and maintenance.

EMBL Barcelona will provide access to state-of-the art technologies for imaging and modelling of tissues and organs, including a facility to grow organoids, mini-versions of real organs produced in vitro. Researchers will also use computers to model diseases in organs and tissues. This opens great opportunities scientifically, says Serrano; for CRG, its a nice way to grow critical mass in the field, he adds. One of the biggest frontiers in biology is trying to understand organ functioning, [both] from an intellectual and medical point of view.

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By Hub staff report

Three Johns Hopkins juniors who have demonstrated outstanding promise in research careers have been recognized by the national Goldwater Scholarship program.

Alfred Chin, Duy Phan, and Fernando Vicente were named Goldwater Scholars. A fourth Johns Hopkins student, Darius Mostaghimi, received honorable mention recognition.

Established in 1986, the Goldwater Scholarship was one of the first significant national scholarships focusing on STEM fields (science, technology, engineering, and math). Winners are nominated by their schools and selected for their academic merit. This year, 250 scholarships were awarded to students from an applicant pool of 1,286.

The program awards winners $7,500 to apply toward tuition, fees, books, and room and board. The national recognition has also been known to give students a competitive edge when pursuing graduate fellowships in their fields.

The four Johns Hopkins students recognized this year are:

Alfred C. Chin, a neuroscience and biophysics double major. He has worked in the lab of neuroscientist Solomon Snyder the School of Medicine since the fall of his freshman year, studying cell signaling pathways involving inositol phosphate kinases. Increasingly curious about the structural and molecular bases of cellular signaling, Chin also joined the lab of biophysicist Albert Lau a year ago to explore the structural biology of ionotropic receptors. He plans to pursue an MD/PhD in pharmacology and eventually to lead a university research lab.

Duy Phan, a neuroscience major and a Woodrow Wilson Research Fellow. Phan has been working in biologist Samer Hattar's lab since his freshman year, focusing on the neural mechanisms by which stressful light environments impair brain function, inspired by previous research at Ohio State on neural development. Phan has also sought out summer research experiences elsewhere to expand his skills in using virus and mouse genetics to study neural circuits, as an HHMI Undergraduate Scholar at Janelia Research Campus and as a Gilman Scholar at the RIKEN Brain Science Institute Summer Program in Tokyo. Last summer, Phan was named an NIH Undergraduate Scholar. He intends to pursue an MD/PhD.

Fernando Vicente, who studies biomedical engineering with a focus in computational biology. Anchored in Jonathan Schneck's lab for the past two years, Fernando has been involved in multiple cell engineering projects, characterizing the interactions of stimulating antigen-presenting cells and immune system T cells. He will soon join Andrew Feinberg's epigenetics lab at the School of Medicine, where he will work on mathematical analysis and predictor models of epigenetics dynamics. Fernando will pursue a PhD in biostatistics and hopes to join the field of epigenetics with an emphasis on big data analysis.

Darius Mostaghimi, a molecular and cellular biology major, who received an honorable mention in the Goldwater competition. Following a summer research experience at Yale, Darius joined John Kim's lab in the Department of Biology during his sophomore year and has worked on small RNAs in nematodes. Darius is also pursuing a second major in history. He intends to pursue an MD/PhD in molecular biology.

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Three Johns Hopkins juniors named Goldwater Scholars - The Hub at Johns Hopkins

April 10, 2017 at 11:03 PM

Like private investigators on a stake out, St. Jude Children's Research Hospital scientists used patience and video surveillance-like tools to identify cells that trigger blood cell development. The findings offer clues for making blood-forming stem cells in the laboratory that may ultimately help improve access to bone marrow transplantation.

"The research will likely open new avenues of investigation in stem cell biology and blood development and provide insight to aid efforts to make transplantable hematopoietic stem cells in the lab," said corresponding author Wilson Clements, Ph.D., an assistant member of the St. Jude Department of Hematology. The research appears today in the journal Nature Cell Biology.

Blood-forming stem cells are capable of making any type of blood cell in the body. They are also used in transplant therapies for cancers like leukemia or other blood diseases like sickle cell. They are starting to be used to deliver gene therapy. However, a shortage of suitable donors limits access to treatment, and efforts to produce blood from pluripotent stem cells in the laboratory have been unsuccessful. Pluripotent stem cells are the master cells capable of making any cell in the body.

All blood-forming stem cells normally arise before birth from certain endothelial cells found in the interior blood vessel lining of the developing aorta. This process--including how endothelial cells are set on the path to becoming blood stem cells--is not completely understood.

Clements and first author Erich Damm, Ph.D., a St. Jude postdoctoral fellow, have identified trunk neural crest cells as key orchestrators of the conversion of endothelial cells to blood stem cells. Trunk neural crest cells are made in the developing spinal cord and migrate throughout the embryo. They eventually give rise to a variety of adult cells, including neurons and glial cells in the sympathetic and parasympathetic nervous system, which control feeding, fighting, fleeing and procreating.

Using time-lapse video, the researchers tracked the migration of neural crest cells in the transparent embryos of zebrafish. Zebrafish and humans share nearly identical blood systems, as well as the programming that makes them during development. After about 20 hours, the neural crest cells had reached the developing aorta. After hour 24, the migrating cells had cozied up to the endothelial cells in the aorta, which then turned on genes, such as runx1, indicating their conversion to blood stem cells.

The investigators used a variety of methods to show that disrupting the normal migration of neural crest cells or otherwise blocking their contact with the aorta endothelial cells prevented the "birth" of blood stem cells. Meanwhile, other aspects of zebrafish development were unaffected.

"Researchers have speculated that the endothelial cells that give rise to blood-forming stem cells are surrounded by a support 'niche' of other cells whose identity and origins were unknown," Damm said. "Our results support the existence of a niche, and identify trunk neural crest cells as an occupant."

Adult bone marrow includes niches that support normal function and notably feature cells derived from trunk neural crest cells.

The findings also suggest that trunk neural crest cells use a signal or signals to launch blood stem cell production during development. The researchers have eliminated adrenaline and noradrenaline as the signaling molecules, but work continues to identify the signaling proteins or small molecules involved.

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Scientists use time-lapse video to identify cells that trigger blood stem cell development - News-Medical.net

M

ice that walk straight and fluidly dont usually make scientists exult, but these did: The lab rodents all had a mouse version of Parkinsons disease and only weeks before had barely been able to lurch and shuffle around their cages.

Using a trick from stem-cell science, researchers managed to restore the kind of brain cells whose death causes Parkinsons. And the mice walked almost normally.The same technique turned human brain cells, growing in a lab dish, into the dopamine-producing neurons that are AWOL in Parkinsons, scientists at Swedens Karolinska Institute reportedon Monday in Nature Biotechnology.

Success in lab mice and human cells is many difficult steps away from success in patients. The study nevertheless injected new life into a promising approach to Parkinsons that has suffered setback after setback replacing the dopamine neurons that are lost in the disease, crippling movement and eventually impairing mental function.

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This is not going to happen in five years or possibly even 10, but Im excited about the potential of this kind of cell replacement therapy, said James Beck, chief scientific officer of the Parkinsons Foundation, which was not involved in the study. It could really give life back to someone with Parkinsons disease.

There is no cure for Parkinsons, a neurodegenerative disease that affects an estimated 10 million people worldwide, most prominently actor Michael J. Fox. Drugs that enable the brain to make dopamine help only somewhat, often causing movement abnormalities called dyskinesia as well as bizarre side effects such as a compulsion to gamble; they do nothing to stop the neurodegeneration.

As Parkinsons patients wait, Fox Foundation and scientist feud over drug trial

Rather than replacing the missing dopamine, scientists led by Karolinskas Ernest Arenas tried to replace dopamine neurons but not in the way that researchers have been trying since the late 1980s. In that approach, scientists obtained tissue containing dopamine neurons from first-trimester aborted fetuses and implanted it intopatients brains.Although a 2001clinical trialfound that the transplants partly alleviated the rigidity and tremors of Parkinsons, the procedure caused serious dyskinesia in about 20 percent of patients, Beck said. More problematic is that fetal issue raises ethical concerns and is in short supply.

It was clear that usable fragments of brain tissue were extremely difficult to recover, said Dr. Curt Freed, of the University of Colorado, who pioneered that work.

Instead, several labs have therefore used stem cells to produce dopamine neurons in dishes. Transplanted into the brains of lab rats with Parkinsons, the neurons reduced rigidity, tremor, and other symptoms. Human studies are expected to begin in the US and Japan this year or next, Beck said.

In the Karolinska approach, there is no need to search for donor cells and no cell transplantation or [need for] immunosuppression to prevent rejection, Arenas told STAT. Instead, he and his team exploited one of the most startling recent discoveries in cell biology: that certain molecules can cause one kind of specialized cell, such as a skin cell, to pull a Benjamin Button, aging in reverse until they become like the embryonic cells called stem cells. Those can be induced to morph into any kind of cell heart, skin, muscle, and more in the body.

Muhammad Ali and Parkinsons disease: Was boxing to blame?

Arenas and his team filled harmless lentiviruses with a cocktail of four such molecules. Injected into the brains of mice with Parkinsons-like damage, the viruses infected plentifulbrain cells called astrocytes. (The brains support cells, astrocytes perform jobs like controlling blood flow.)The viruses also infected other kinds of cells, but their payload was designed to work only in astrocytes, and apparently caused no harm to the other cells.

The molecules, called transcription factors, reprogrammed some of the astrocytes to become dopamine neurons, which were first detected three weeks later in the mouse brains. The dopamine neurons were abundant 15 weeks later, an indication that after changing into dopamine neurons the astrocytes stayed changed.

Five weeks after receiving the injections, the mice, which used to have Parkinsons-like gait abnormalities, walked as well as healthy mice. That suggests that direct reprogramming [of brain cells] has the potential to become a novel therapeutic approach for Parkinsons, Arenas told STAT.

That could have value for preserving the brain circuitry destroyed by Parkinsons, said Colorados Freed.

A lot of hurdles need to be overcome before this becomes a Parkinsons treatment. The Trojan horse system for delivering the reprogramming molecules inside viruseswould need to turn more astrocytes into dopamine neurons and leave other kinds of cells alone: Although viruses getting into mouse brain cells apparently caused no harm, that might not be so in people. We will need to use virus with selective [attraction] for astrocytes, Arenas said.

The morphed cells would presumably be ravaged by whatever produced Parkinsons in the first place. But in other cell transplants, Arenas said, the disease catches up with transplanted cells in 15 to 20 years, buying patients a good period of time. He thinks it might be possible to give patients a single injection but hold off some of the reprogramming with a drug, turning it on when the brain again runs short of dopamine neurons.

The basic technology to develop such strategies currently exists, he said.

The Karolinska lab is working to make the techniquesafer and more effective, including by using viruses that would deliver reprogramming molecules only to astrocytes. We are open to collaborations aimed at human studies, Arenas said.

Would patients be willing to undergo brain injections? People with Parkinsons disease, Beck said, are willing to go through a lot for any hope of improvement.

Sharon Begley can be reached at sharon.begley@statnews.com Follow Sharon on Twitter @sxbegle

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Mighty morphed brain cells cure Parkinson's in mice, but human trials still far off - STAT

At the University of Washingtons Institute for Stem Cell and Regenerative Medicine, scientists and physicians are manipulating stem cells to heal and restore the function of hearts, eyes, kidneys and other tissues.

IF you have a heart attack, hopefully youll survive. But your body will be forever changed. The worlds best doctors cant undo the damage; instead, drugs and devices will help you live with a heart whose function too often dwindles.

The body cannot replace muscle cells that die in heart attacks maladies that help make heart failure the No. 1 global cause of death and our nations biggest health care expense. These patients face daily medication, decreased energy and, for the lucky 0.1 percent, the ability to qualify for an extraordinarily costly heart transplant and anti-rejection medication that also leaves them more vulnerable to other diseases.

Thanks to medical advances, heart failure has become a chronic condition that people are now managing for decades. The same is true for diabetes, kidney disease and arthritis. But with that longevity comes a tether to drug regimens whose costs rise seemingly at whim.

Dr. Charles Murry is interim director of UW Medicines Institute for Stem Cell and Regenerative Medicine.

These chronic diseases are a major reason that health-care costs hold center stage in Americans consciousness.

Amid our collective uncertainty, medical science offers one path of relief. Specifically, the engineering of human cells and tissues to restore vitality to poorly functioning organs.

The medical conditions named above share a common root not addressed by todays best care: The body is missing a population of cells that do critical work. If we could restore that population, we could cure many chronic diseases.

At the University of Washingtons Institute for Stem Cell and Regenerative Medicine (ISCRM), scientists and physicians are manipulating stem cells to heal and restore the function of hearts, eyes, kidneys and other tissues.

This year, we also seek a first-time investment from our state Legislature.

Weve pioneered techniques to grow unlimited human heart muscle cells in the lab. We were the first to transplant these cells into injured hearts and repair the injury with new tissue growth. UW Medicine will begin first-in-human tests of these cells in Seattle in 2019.

If this one and done treatment prevents heart failure in even the sickest 10 percent of heart-attack patients, our nation could save a staggering $3.5 billion per year in health-care costs. More importantly, these patients will lead longer, healthier, more productive lives.

Other ISCRM scientists are pursuing a gene therapy for muscular dystrophy, a devastating illness that often strikes young boys. The therapy, tested in Labrador puppies that were paraplegic as a result of the same, naturally occurring muscle-wasting disease, had the dogs leaping and frolicking in just weeks. A clinical trial is planned for 2018.

We are similarly probing therapies for cancer, kidney failure, diabetes and Alzheimers. And were doing this with the Northwests entrepreneurial spirit: In the past decade, ISCRM has patented 250+ discoveries with commercial potential and started 20 companies.

Legislatures in at least 11 other states, including California, New York, Wisconsin, Minnesota and Maryland, have invested cumulative billions in regenerative medicine. Most of that funding has gone to university-based research centers like ours.

To this point there has been no state investment in ISCRM. Nevertheless we have built a world-class program with federal grants and private philanthropy. But those dollars come in boom-and-bust cycles, and what we need now is stable funding to maintain competitiveness.

For this reason, the UW seeks $6 million in operating funds from the Legislature, starting with the next biennium, to recruit and retain top scientists, fund promising results at early stages, and train young researchers and clinicians.

We are grateful, at this juncture, that the state Senate included us in its initial budget.

We ask all legislators to invest in the health of our residents and in the promise of what weve accomplished so far. With stem-cell biology, we are ready to rebuild solid tissues like the heart and potentially cure our nations greatest cause of death and health-care expense.

Clinical success will make Washington a destination for heart repair and other regenerative therapies. This race is ours to lose.

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Pioneering work on stem-cell therapies at UW deserves state support - The Seattle Times