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Archive - Jun 17, 2015

Capricor Therapeutics Appoints Dr. Houmann Hemmati As VP of Medical & Clinical Development for New Therapies; Capricor Efforts Include Working to Bring New Exosome Platforms into Clinical Development in 2016

On June 17, 2015, Capricor Therapeutics, Inc. (Nasdaq:CAPR) (, a Beverly Hills, California biotechnology company focused on the discovery, development, and commercialization of first-in-class therapeutics for the treatment of diseases, announced the appointment of Houman Hemmati (image), M.D., Ph.D., to the newly created position of Vice President of Medical and Clinical Development for New Therapies. In this role, Dr. Hemmati will work to drive promising new therapies such as Capricor's exosome platform into clinical development as he works closely with the R&D, manufacturing, and product development teams. "Dr. Hemmati strengthens our team with valuable clinical development experience having driven multiple key high-profile products through the clinical trial process prior to joining Capricor. This timely addition to our management team comes as we expand our platform and work to bring new exosome therapeutics into clinical development next year," said Linda Marbán, Ph.D., Chief Executive Officer of Capricor. "Our exosomes, which are nanometer-sized vesicles packed full of RNAs, have demonstrated exciting capabilities to date including the ability to enact various structural and functional changes therapeutically beneficial in animal models. Further our exosomes offer a broad spectrum of therapeutic potential primarily focused on their anti-inflammatory and anti-fibrotic properties that we are now poised to further develop." Prior to joining Capricor, Dr. Hemmati, an ophthalmologist, was Director of Clinical Development at Allergan, where his responsibilities included early- to late-stage clinical trial development of high-profile ophthalmic products such as Restasis-X as well as Allegan's androgen-based ophthalmic treatment and AGN 199201 for presbyopia. Prior to his time at Allergan, Dr.

Higher Consumption of Dietary Trans Fats Linked to Worsened Memory Function in Males 45 and Younger; “Trans Fats Prolong Shelf Life of Food, But Reduce Shelf Life of People,” Author States

Higher consumption of dietary trans fatty acids (dTFA), commonly used in processed foods to improve taste, texture, and durability, has been linked to worsened memory function in men 45 years old and younger, according to a University of California (UC), San Diego School of Medicine study published online on June 17, 2015 in the open-access journal PLOS ONE. The article is titled “A Fat to Forget: Trans Fat Consumption and Memory.” Researchers evaluated data from 1,018 men and women who were asked to complete a dietary survey and memory test involving word recall. On average, men aged 45 and younger recalled 86 words; however, for each additional gram of trans fats consumed daily, performance dropped by 0.76 words. This translates to an expected 12 fewer words recalled by young men with dTFA intake levels matching the highest observed in the study, compared to otherwise similar men consuming no trans fats. "Trans fats were most strongly linked to worse memory in men during their high productivity years," said Beatrice A. Golomb, M.D., Ph.D., lead author and Professor of Medicine at the UC San Diego School of Medicine. "Trans fat consumption has previously shown adverse associations to behavior and mood--other pillars of brain function. However, to our knowledge a relation to memory or cognition had not been shown." After adjusting for age, exercise, education, ethnicity and mood, the link between higher dTFA and poorer memory was maintained in men 45 and younger. The study focused predominantly on men because of a small number of women in this age group. However, including women in the analysis did not change the finding, said Dr. Golomb. An association of dTFA to word memory was not observed in older populations. Dr. Golomb said this is likely due to dietary effects showing more clearly in younger adults.

Epigenetic Angle on Melanoma: High Levels of H2A.Z.2 Histone Variant Promote Melanoma Growth; Blocking H2A.Z.2 Function Halts Tumor Growth and Kills Melanoma Cells

Melanoma patients with high levels of a histone variant protein that controls the expression of pro-growth genes are less likely to survive, according to a study led by researchers at the Icahn School of Medicine at Mount Sinai and published online on June 4, 2015 in the journal Molecular Cell. The article is titled “Histone Variant H2A.Z.2 Mediates Proliferation and Drug Sensitivity of Malignant Melanoma.” “The research team found that the protein, a histone variant called H2A.Z.2, promotes the abnormal growth seen in melanoma cells as they develop into difficult-to-treat tumors. H2A.Z.2 is part of the chromosome structure (histones) that packages genes, and has the ability to switch them on and off. Having high levels of this protein aberrantly activates growth-promoting genes in melanoma cells. An emerging theory in cancer research is that abnormal growth may result, not only from unfortunate mutations in patients' genes, but also from epigenetic mechanisms that turn genes on and off. In the current study, the authors found that blocking the functions of H2A.Z.2, either alone or in combination with cancer therapies, effectively blocked tumor growth and killed melanoma cells. "Cancer is a disease consisting of both genetic and epigenetic changes," said Emily Bernstein, Ph.D., Associate Professor of Oncological Sciences and Dermatology, at the Icahn School of Medicine at Mount Sinai, and lead author of the current study. "I believe that the study of epigenetic mechanisms may lead to the development of new approaches for molecular diagnosis and targeted treatments. Here we show that the histone variant H2A.Z.2 drives melanoma progression by affecting chromatin structure," said Dr. Bernstein. "This is the first study to identify a specific role for the histone variant H2A.Z.2 in any tumor type.

Human Brains Are Wired to Convert Smells into Spatial Information, Providing Surprising 3-D Olfactory Orientation Ability; Humans Can Orient & Navigate Themselves Along Highways of Odors

Like homing pigeons, humans have a nose for navigation because our brains are wired to convert smells into spatial information, new research from the University of California (UC), Berkeley, shows. While humans may lack the scent-tracking sophistication of, say, a search-and-rescue dog, we can sniff our way, blindfolded, toward a location whose scent we've smelled only once before, according to the UC Berkeley study published online on June 17, 2015 in the open-access journal PLOS ONE. The article is titled “Olfactory Orientation and Navigation in Humans.” Similar investigations have been conducted on birds and rodents, but this is the first time smell-based navigation has been field-tested in humans. The results evoke a GPS-like superpower one could call an "olfactory positioning system." "What we've found is that we humans have the capability to orient ourselves along highways of odors and crisscross landscapes using only our sense of smell," said study lead author Dr. Lucia Jacobs, a UC Berkeley Psychology Professor who studies evolution and cognition in animals and humans. Smell is a primitive sense that our early ancestors used for foraging, hunting, and mating, among other skills necessary for survival. Early sailors and aviators gave anecdotal reports of using odors to navigate, but there have been no experiential scientific studies on this until now. The process of smelling, or olfaction, is triggered by odor molecules traveling up the nasal passage, where they are identified by receptors that send signals to the olfactory bulb - which is located between the nasal cavity and the brain's frontal lobe - and which processes the information.

Songbird Targets of Brood Parasite Cuckoos Generate Complicated and Unpredictable Color Patterns on Their Eggs to Reduce Interloper Risk; Key Study of Eggs Collected by Retired British Major Occasionally Interrupted by Passing Baboons

There's a high-stakes arms race being waged with colors and patterns in the scrublands of southern Zambia. It's a battle that's probably being fought everywhere that there are birds practicing what is known as "brood parasitism," i.e., laying their eggs in the nests of another bird species. In a new study, published online in an open-access article on June 17, 2015 in the Proceedings of the Royal Society B, current Duke University graduate student Eleanor Caves found that African songbirds that are frequently victimized by brood parasitic cuckoos have taken to creating elaborate patterns on their eggs to help them recognize the forgeries. This article also serves as the cover story for the July 2015 print issue of the Proceedings of the Royal Society B. The article is titled “Hosts of Brood Parasites Have Evolved Egg Phenotypic Signatures with Elevated Information Content.” But of course this host strategy does not work perfectly, or the war would be over. During her master's research at the University of Cambridge in the UK, Caves methodically examined how two kinds of songbirds pattern their eggs to try to stay one step ahead of two species of parasitic birds. "We don't know at what stage of this evolutionary arms race we're seeing these species," Caves said, but her study has found that birds that are heavily parasitized are able to "sign" their eggs with color and pattern traits in unpredictable combinations. The hundreds of eggs used in her study (see image) had been meticulously collected and catalogued by a retired British military officer, Major John F.R. Colebrook-Robjent, on his ranch in the Choma district of Southern Zambia over a 35-year period. He painstakingly drilled and blew out each of the tiny eggs, and marked them with a set number to indicate which ones belonged in the same clutch.

As Insect Societies Evolved, Brain Regions for Central Cognitive Processing Shrank; This Contrasts Sharply with Evolution of Vertebrate Societies That Is Associated with Brain Expansion

The society you live in can shape the complexity of your brain--and it does so differently for social insects than for humans and other vertebrate animals. A new comparative study of social and solitary wasp species suggests that, as social behavior evolved, the brain regions (mushroom bodies) for central cognitive processing in social insect species shrank. This is the opposite of the pattern of brain expansion with sociality that has been documented for several kinds of vertebrate animals, including mammals, birds, and fish. "By relying on group mates, insect colony members may afford to make less individual brain investment. We call this the ‘distributed cognition hypothesis,’" said Sean O'Donnell, Ph.D., a Professor at the Drexel University College of Arts and Sciences in Philadelphia, Pennsylvania, who led the study published on June 17, 2015 in Proceedings of the Royal Society B. The article is titled “Distributed Cognition and Social Brains: Reductions in Mushroom Body Investment Accompanied the Origins of Sociality in Wasps (Hymenoptera: Vespidae).” A highly informative video is also available at the following link: Essentially, Dr. O'Donnell says, the cooperative or integrative aspects of insect colonies, such as information sharing among colony mates, can reduce the need for individual cognition in these societies. The “distributed cognition hypothesis” contrasts sharply with the leading models of how the social complexity of vertebrate animals relates to their cognitive abilities. In vertebrates, more complex social environments generally demand more complex cognitive abilities in individuals.

Stress Can Alter Mother’s Vaginal Microbiome and Have Major Effects on Offspring’s Gut Microbiota, Immune System Maturation, and Brain Development

Changes in the vaginal microbiome are associated with effects on offspring gut microbiota and on the developing brain, according to a new study published online on June 16, 2015 in an open-access article in Endocrinology, a journal of the Endocrine Society. The article is titled “'Alterations in the Vaginal Microbiome by Maternal Stress Are Associated with Metabolic Reprogramming of the Offspring Gut and Brain.” The neonate is exposed to the maternal vaginal microbiota during birth, providing the primary source for normal gut colonization, host immune maturation, and metabolism. These early interactions between the host and microbiota occur during a critical window of neurodevelopment, suggesting that early life is an important period of cross-talk between the developing gut and brain. “Mom's stress during pregnancy can impact her offspring's development, including the brain, through changes in the vaginal microbiome that are passed on during vaginal birth,” said one of the study's authors, Tracy Bale, Ph.D., of the University of Pennsylvania. “As the neonate's gut is initially populated by the maternal vaginal microbiome, changes produced by maternal stress can alter this initial microbe population, as well as determine many aspects of the host's immune system that are also established during this early period.” In this study, researchers utilized an established mouse model of early maternal stress, which included intervals of exposure to a predator odor, restraint, and novel noise as stressors. Two days after birth, tissue was collected from the moms using vaginal lavages, and maternal fecal pellets and offspring distal gut were then analyzed. Offspring brains were examined to measure transport of amino acids.

Urocortin3 Hormone Plays Key Role in Negative Feedback Control of Insulin Secretion; Urocortin3 Levels Reduced in Animal Models of Diabetes and in Beta Cells of Diabetes Patients

Sometimes, listening in on a conversation can tell you a lot. For Dr. Mark Huising, an Assistant Professor in the Department of Neurobiology, Physiology, and Behavior at the University of California (UC) Davis College of Biological Sciences, that crosstalk is between the cells that control your body's response to sugar, and understanding that conversation can help us understand, and perhaps ultimately treat, diabetes. Dr. Huising's laboratory team has now identified a key part of the conversation going on between cells in the pancreas. A hormone called urocortin3, the scientists found, is released at the same time as insulin and acts to damp down insulin production. A paper describing the work was published online on June 15, 2015 in Nature Medicine. The article is titled “Urocortin3 Mediates Somatostatin-Dependent Negative Feedback Control of Insulin Secretion." "It's a beautiful system," Dr. Huising said. "It turns out that there is a lot of crosstalk going on in the islets to balance insulin and glucagon secretion. The negative feedback that urocortin3 provides is necessary to tightly control blood sugar levels at all times." Diabetes affects millions of Americans every year. Both forms of the disease -- type 1, "juvenile" or "insulin-dependent" diabetes, and type 2 or "adult-onset" diabetes – cause the body to be unable to regulate the level of glucose properly. Diabetes is tied to structures called the Islets of Langerhans in the pancreas. Within the islets, so-called “beta cells” make insulin. Increasing blood sugar stimulates insulin production, which is secreted from the pancreas and causes the body's cells to pull sugar out of circulation. The islets also house alpha cells, which make another hormone, glucagon, which acts on the liver, causing it to release more glucose into the bloodstream.

New Mouse Model Developed for Spinocerebellar Ataxia Type 6, a Polyglutamine Disease Like Huntington’s; Simple Eye Blink Conditioning Test May Provide Early Diagnosis

Scientists at the Ruhr-Universität Bochum in Germany have established a mouse model for the human disease spinocerebellar ataxia type 6 (SCA6). SCA6 is characterized by movement deficits and caused by similar genetic alterations as Huntington’s disease. The mouse model will be used to investigate the disease mechanisms. Experiments suggest that an impairment of eye blink conditioning could be an early disease symptom. The team from the Department of Zoology and Neurobiology published its data in the June 10, 2015 issue of The Journal of Neuroscience and the work was highlighted by an editor’s commentary. The article is titled “Spinocerebellar Ataxia Type 6 Protein Aggregates Cause Deficits in Motor Learning and Cerebellar Plasticity.” The researchers noted that SCA6 is a movement disorder that results in the loss of a special type of neuron in the cerebellum called Purkinje cells. These neurons process sensory information to coordinate movements. The disease has a late onset and develops in the second period of life. Patients are often wheelchair-bound and no therapies are available. “To understand, how the disease originates and progresses and to develop new therapeutic strategies, it was important to establish a new mouse model,” says Dr. Melanie Mark, a neuroscientist from the Ruhr-Universität Bochum and lead author of the Journal of Neuroscience article. The researchers said that SCA6 belongs, together with Huntington’s disease, to the family of polyglutamine diseases. These diseases are characterized by repetitions of the amino acid glutamine in disease-specific proteins. The team of Professor Dr. Stefan Herlitze used a human calcium channel fragment from a SCA6 patient containing stretches of glutamine and inserted it in cerebellar Purkinje cells of mice.

Scientists Identify Protein That Can Reverse Pulmonary Arterial Hypertension (PAH) in Multiple Animal Models and Human in Vitro Tests; May Prove a Cure for This Chronic, Debilitating Disease, Both Genetic and Idiopathic

A protein that targets the effects of a faulty gene could offer the first treatment targeting the major genetic cause of pulmonary arterial hypertension (PAH), according to research funded by the British Heart Foundation (BHF) and carried out at the University of Cambridge in the UK. Genetic evidence dating back to 2000, from research the BHF helped to fund, indicated that the absence or reduced activity of a particular protein, bone morphogenetic protein type II receptor (BMPR-II), leads to PAH. BMPR-II is important to the normal function of the blood vessels of the lungs. PAH is believed to affect approximately 6,500 people in the UK. This new study led by BHF Professor of Cardiopulmonary Medicine Dr. Nick Morrell and including expertise from Dr. Rajiv Machado at the University of Lincoln, UK, is the first to use a protein, called bone morphogenetic protein 9 (BMP9), to reverse the effects of reduced activity of BMPR-II and to reverse the PAH disease itself. The study was conducted in mice and rats, but also using cells from patients with PAH. It was published online on June 15, 2015 in Nature Medicine. The article is titled “Selective Enhancement of Endothelial BMPR-II with BMP9 Reverses Pulmonary Arterial Hypertension.” PAH is a chronic and debilitating disease that affects the blood vessels in the lungs, leading to heart failure, and leaving sufferers feeling breathless and exhausted. Current treatments only target the symptoms and prognosis remains poor. The only effective cure is a lung, or heart and lung, transplant, which has associated risks and complications. Once diagnosed with PAH, a person has a 30 per cent chance of dying within three years and the condition affects more women than men.