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Archive - Mar 3, 2017

Progeria-on-a-Chip Model Offers Insights into Premature Aging and Vascular Disease

Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic condition that causes premature and accelerated aging. Recently, researchers have been able to generate induced pluripotent stem cells from patients with HGPS to better understand the mechanisms of aging and look for new treatments. HGPS primarily affects vascular cells, which undergo biomechanical strains in blood vessels. However, the impact of these biomechanical strains on aging and vascular diseases has been challenging to study in the lab as most models fail to mimic the biomechanics that cells experience in the body. Using a new progeria-on-a-chip model, investigators from Brigham and Women's Hospital, led by João Ribas, Ph.D. candidate, and Ali Khademhosseini, Ph.D., of the Biomaterials Innovation Research Center, have developed a way to recapitulate blood vessel dynamics to better understand vascular disease and aging. The new organ-on-a-chip device consists of a top fluidic channel and underlying vacuum channel, which mimics, upon pressure, the mechanical stretching that cells experience within blood vessels. The team found that cells derived from HGPS donors, but not from healthy donors, showed an exacerbated response to biomechanical strain, with an increase in markers of inflammation, which are strongly associated with vascular disease and aging. "Vascular diseases and aging are intimately linked yet rarely studied in an integrated approach," the authors write. "Gaining a deeper understanding of the molecular pathways regulating inflammation during vascular aging might pave the way for new strategies to minimizing cardiovascular risk with age." The open-access article, titled “Biomechanical Strain Exacerbates Inflammation on a Progeria-on-a-Chip Model," was published on February 17, 2017 in the journal Small.

Ten Million Lives Saved Globally by Vaccination Since Hayflick’s 1962 Development of Normal Human Cell Strain for Safe Vaccine Production; Data Marshalled in Opposition to Anti-Vaccine Movement

Nearly 200 million cases of polio, measles, mumps, rubella, varicella, adenovirus, rabies, and hepatitis A (and approximately 450,000 deaths from these diseases) were prevented in the U.S. alone between 1963 and 2015 by vaccination, researchers estimate. The study was published online on February 28, 2017 in AIMS Public Health. In 1963, vaccination against these infections became widespread, thanks to the development of a human cell strain that allowed vaccines to be produced safely. Globally, the vaccines developed from this strain and its derivatives prevented an estimated 4.5 billion cases of disease and saved more than 10 million lives. Author S. Jay Olshansky, Ph.D., Professor of Epidemiology and Biostatistics at the University of Illinois at Chicago (UIC) School of Public Health, was approached by co-author Leonard Hayflick, Ph.D., of the University of California, San Francisco (UCSF), who wanted to know how many lives had been saved by his development of cell strain WI-38. Hayflick developed the normal human cell strain in 1962, and it has been used ever since to safely grow the viruses needed to produce vaccines against more than 10 diseases. Before then, many viral vaccines had been grown in monkey cells, but contamination with potentially dangerous monkey viruses forced an end to this form of production, leaving millions vulnerable to common diseases. "Given the acknowledged large, positive global health impact of vaccines in general, I was curious what contribution my discovery of WI-38 in 1962 had in saving lives and reducing morbidity, since a large number of viral vaccines in use today are made with my cell strain or its derivatives," Dr. Hayflick said. To determine the number of cases of disease and deaths prevented by vaccines developed using WI-38, Dr.

Why Giant Pandas Are Black and White

The scientists who uncovered why zebras have black and white stripes (to repel biting flies), took the coloration question to giant pandas in a study published on February 28, 2017 in the journal Behavioral Ecology. The study, a collaboration between the University of California (UC), Davis, and California State University (CSU), Long Beach, determined that the giant panda's distinct black-and-white markings have two functions: camouflage and communication. "Understanding why the giant panda has such striking coloration has been a long-standing problem in biology that has been difficult to tackle because virtually no other mammal has this appearance, making analogies difficult," said lead author Tim Caro, a professor in the UC Davis Department of Wildlife, Fish and Conservation Biology. "The breakthrough in the study was treating each part of the body as an independent area." This enabled the team to compare different regions of fur across the giant panda's body to the dark and light coloring of 195 other carnivore species and 39 bear subspecies, to which it is related. Then they tried to match the darkness of these regions to various ecological and behavioral variables to determine their function. Through these comparisons, the study found that most of the panda - its face, neck, belly, rump -- is white to help it hide in snowy habitats. The arms and legs are black, helping it to hide in shade. The scientists suggest that this dual coloration stems from its poor diet of bamboo and inability to digest a broader variety of plants. This means it can never store enough fat to go dormant during the winter, as do some bears. So it has to be active year-round, traveling across long distances and habitat types that range from snowy mountains to tropical forests.

“Red Hair” Gene Variant May Underlie Association Between Melanoma & Parkinson's Disease

A gene variant that produces red hair and fair skin in humans and in mice, and which increases the risk of the dangerous skin cancer melanoma, may also contribute to the known association between melanoma and Parkinson's disease. In a paper appearing in the March 2017 issue of Annals of Neurology and previously published online (January 23, 2017), Massachusetts General Hospital (MGH) investigators report that mice carrying the red-hair variant of the melanocortin 1 receptor (MC1R) gene have reduced production of the neurotransmitter dopamine in the substantia nigra [the brain structure in which dopamine-producing neurons are destroyed in Parkinson's disease (PD)] and are more susceptible to toxins known to damage those neurons. "This study is the first to show direct influences of the melanoma-linked MC1R gene on dopaminergic neurons in the brain and may provide evidence for targeting MC1R as a novel therapeutic strategy for PD," says Xiqun Chen, M.D., Ph.D., of the MassGeneral Institute for Neurodegenerative Disease (MGH-MIND), lead and corresponding author of the report. "It also forms a foundation for further interdisciplinary investigations into the dual role of this gene in tumorigenesis within melanocytes (the pigment cells in which melanoma develops) and the degeneration of dopaminergic neurons, improving our understanding of why and how melanoma and Parkinson's disease are linked." Inherited variants of the MC1R gene determine skin pigmentation, with the most common form leading to greater production of the darker pigment called eumelanin and the red-hair-associated variant, which inactivates the gene's function, increasing production of the lighter pigment called pheomelanin.

New Technique Removes Cause of Allergic Asthma: IgE Antibodies Immuno-Adsorbed on Sepharose Column

Allergies are the most common cause of asthma. The immune system over-reacts to harmless substances such as birch or grass pollen, for example, forming immunoglobulin E antibodies (IgE). Together with the inflammatory cells in the skin and mucous membranes (the "mast cells"), IgE antibodies are responsible for certain allergic diseases, such as asthma and hay fever, for example, and are also partly responsible for the development of neurodermatitis. Scientists from MedUni Vienna have now successfully developed a technique for suctioning the IgE antibodies out of the blood, thereby significantly improving the quality of life for people who suffer from severe allergic asthma. The "IgEnio" column was developed for this purpose. This one-way adsorber, which has been specifically developed for treating IgE-related diseases, reduces the plasma IgE level by running the patient's blood through a "column" that traps the IgE antibodies – by means of Sepharose beads carrying IgE-binding proteins. These beads bind IgE in the column, thereby adsorbing the antibodies as the blood flows through during "dialysis." There is also a similar absorber for IgG antibodies, for treating autoimmune diseases. In the first study conducted with IgEnio, the MedUni Vienna researchers at the Institute of Pathophysiology and Allergy Research, led by Dr. Rudolf Valenta and lead author Dr. Christian Lupinek, Dr. Kurt Derfler from the Division of Nephrology and Dialysis (Department of Medicine III), and Dr. Ventzislav Petkov from the Division of Pulmonology (Department of Medicine II), were able to show that this absorption technique brings about a significant improvement in the quality of life for sufferers during the pollen season – even those with a greatly elevated IgE levels. The technique removes approximately 80% of the IgE antibodies.

Sickle Cell Disease: Remission of Signs of Disease in First Patient in World Treated with Gene Therapy; NEJM Publishes Case Study; Patient Treated with LentiGlobin Drug Product Is Free from Severe Symptoms & Has Resumed Normal Activities

On March 1, 2017. Bluebird Bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic diseases and T cell-based immunotherapies for cancer, announced publication in the New England Journal of Medicine of positive results of a case study on Patient 1204, the first patient with severe sickle cell disease (SCD) to be treated with gene therapy. The NEJM article is titled ““Gene Therapy in a Patient with Sickle Cell Disease.” This patient, who was 13 years old at the time of treatment, was treated with LentiGlobin drug product in the HGB-205 clinical study conducted in Necker Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France. The data in the publication reflects 15 months of follow-up. A brief summary of this patient’s outcomes with 21 months of follow-up was presented at the 58th American Society of Hematology Annual Meeting in December 2016. “We have managed this patient at Necker for more than 10 years, and standard treatments were not able to control his SCD symptoms. He had to receive blood transfusions every month to prevent severe pain crises,” said Professor Marina Cavazzana, M.D., Ph.D., principal investigator of this study and Professor of Hematology at Paris Descartes University, Head of the Department of Biotherapy Hospital, the clinical research center of Biotherapy at Necker Enfants Malades - Greater Paris University Hospital, AP-HP and INSERM, and of the Lymphohematopoiesis Laboratory, Imagine Institute of Genetic Diseases, Paris, France.