Category Archives: Transhuman News

PUBLIC RELEASE DATE:

3-Feb-2014

Contact: Anita Srikameswaran SrikamAV@upmc.edu 412-578-9193 University of Pittsburgh Schools of the Health Sciences

PITTSBURGH, Feb. 3, 2014 Opening up a can of worms is a good way to start hunting for new drugs, recommend researchers from Children's Hospital of Pittsburgh of UPMC and the University of Pittsburgh School of Medicine. In a study published today in the Public Library of Science One, they used a primitive worm model to show that a drug typically used to treat agitation in schizophrenia and dementia has potential as a treatment for -1 antitrypsin (AT) deficiency, an inherited disease that causes severe liver scarring.

In the classic form of AT deficiency, which affects 1 in 3,000 live births, a gene mutation leads to production of an abnormal protein, dubbed ATZ, that unlike its normal counterpart is prone to clumping, explained David H. Perlmutter, M.D., physician-in-chief and scientific director, Children's Hospital, and Distinguished Professor and Vira I. Heinz Endowed Chair, Department of Pediatrics, Pitt School of Medicine.

"These protein aggregates accumulate in liver cells and eventually lead to scarring of the organ or to tumor formation," Dr. Perlmutter said. "If we could find a drug that slows or stops this process, we might be able to prevent the need for liver transplantation in these patients."

To find that drug, Dr. Perlmutter's team worked with Pitt's Stephen Pak, Ph.D., assistant professor of pediatrics, and Gary Silverman, M.D., Ph.D., Twenty-five Club Professor of Pediatrics, Cell Biology and Physiology, who developed a model of AT deficiency in Caenorhabditis elegans, or C. elegans, a harmless microscopic worm or nematode typically found in soil. Previous experiments conducted by Drs. Pak and Silverman, in which more than 2,000 compounds were screened, showed that fluphenazine, a drug approved for human use as a mood stabilizer, could reduce ATZ accumulation in the worm, so the team studied it further.

Worms that produce ATZ die sooner than normal ones, which typically have a life span of fewer than 20 days. Those that were exposed to fluphenazine, however, had lower burdens of ATZ and lived more than a day longer that untreated animals. The lifespan of normal worms was unchanged by fluphenazine exposure. The researchers also labeled with fluorescent markers intracellular structures called autophagosomes, which help clear abnormal proteins out of the cell in a process called autophagy. Fluphenazine exposure was associated with a greater presence of autophagosomes, suggesting that increased autophagy led to reduced ATZ accumulation.

Follow-up experiments showed that fluphenazine reduced ATZ accumulation in several mammalian-cell line models of AT deficiency, D. Silverman said.

"We found when we gave this drug for three weeks to mice with the disease, autophagy is activated, the abnormal protein load is diminished, and liver scarring is reversed. It's truly amazing," he said. "And because fluphenazine is already being safely prescribed for other conditions, it should be easier to bring it to clinical trials for AT deficiency."

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Mood-stabilizing drug could treat inherited liver disease, says Pitt/Children's team

Scientists in China have created two monkeys with customized gene mutations. The successful births of the twin macaques, named Ningning and Mingming, may bring researchers closer to being able to recreate such human diseases as Alzheimers and Parkinsons in primates. This would allow scientists to use primates, rather than rodents, as more realistic models of human illness.

To engineer the monkeys, researchers at Nanjing University and Yunnan Key Laboratory of Primate Biomedical Research in Kunming, China, used a new gene-editing technology called Crispr, which allows scientists to insert, delete, or rewrite a specific gene sequence. The technique, which may help usher in a new era of genetic medicine, has previously been used to manipulate the genomes of rats, mice, and zebrafish. But this is reportedly the first time it has been used successfully in primates.

The Chinese researchers altered genes in several fertilized monkey eggs before implanting them in surrogate mothers. (Several surrogates miscarried and some pregnancies are reportedly ongoing.) Newborn Ningning and Mingming have three modified genes: one that regulates metabolism, another that regulates immune cell development, and a third that regulates stem cells and sex determination, according to the MIT Technology Review.

The infant monkeys are too young for researchers to determine the physiological and behavioral effects of their mutations, but scientists worldwide are already looking to create their own Crispr-modified monkeys. Although mice are giving us tremendous insight into basic brain biology and the biology of the disease, theres still a big gap in between the mouse brain and the monkey brain, Robert Desimone, director of MITs McGovern Brain Institute for Brain Research, told the MIT Technology Review. Not to mention that several drugs that work in mice dont work in humans.

Researchers also hope that the possibility of using genetically-modified monkeys will encourage more companies to boost spending on drugs to treat neurological disorders, reversing a recent trend of large pharmaceutical companies pulling back from such risky research. They also say Crispr may eventually be used for human gene therapy to treat inherited diseases such as cystic fibrosis and sickle-cell anemia. The ability to alter DNA is also being investigated as a way to make people resistant to HIV.

Chinas mutant-monkey breakthrough is controversial among animal rights activists. According to PETA, more than 125,000 primates are kept in U.S. laboratories and used for experiments every year.

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China Creates Monkeys With Custom Gene Mutations

PUBLIC RELEASE DATE:

3-Feb-2014

Contact: Vicki Bendure vicki@bendurepr.com 202-374-9259 Society for Maternal-Fetal Medicine

In a study to be presented on Feb. 6 at 2:45 p.m. CST, at the Society for Maternal-Fetal Medicine's annual meeting, The Pregnancy Meeting, in New Orleans, researchers will report that a variant in SERPINE1, a gene involved in inflammation and blood clotting, is associated with cerebral palsy and death in very preterm babies. This gene has been associated with increased risk of cerebral palsy in one previous study of preterm babies.

Previous genetic studies of very preterm babies have suggested several genetic variations that might predispose to brain injury and developmental problems. However, different studies have had different results.

This study, titled Genetic Predisposition to Adverse Neurodevelopmental Outcome After Early Preterm Birth: A Validation Analysis, was a collaborative effort between the Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units and Neonatal Research Networks.

Researchers evaluated two different populations of very early preterm births (earlier than 32 weeks) with the goal of confirming the same genetic risk factors in both groups. The first population of preterm births was enrolled in a large Neonatal Research Network study, and the other group was of births that were enrolled in a Maternal Fetal Medicine Units Network study of magnesium sulfate before preterm birth for prevention of cerebral palsy.

Results revealed a variant in the gene SERPINE1, a gene involved in inflammation and blood clotting, was associated with cerebral palsy and death after early preterm birth in both populations of preterm babies.

"Preterm birth is the leading cause of childhood brain injury in otherwise normal children. The earlier a baby is born, the higher the risk of brain injury. However, even among the tiniest preemies, some babies develop quite normally, while others have devastating brain injury and life-long disability," said Erin Clark, M.D., the study's author. "The reason for this difference in outcomes is not well understood. Genetics may allow identification of babies at increased risk so that we can target those babies for prevention and treatment strategies. These results add to the evidence that genes may play a role in risk of brain injury and death in preterm babies."

Clark, assistant professor of Maternal Fetal Medicine, University of Utah School of Medicine's Department of Obstetrics and Gynecology, also noted that additional research is necessary to further evaluate genes that may influence risk and to determine how to apply these results to clinical care.

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Study associates gene with cerebral palsy and death in very preterm babies