Category Archives: Transhuman News

Physicians have practiced precision medicine, defined as the tailoring of medical treatment by taking into account individual differences in peoples genes, environments and lifestyles, for decades. The main difference today is that technological advances have given us greater power to combine comprehensive data collected over time about an individual to help provide appropriate care.

The precision medicine initiative, now known as the All of Us Research Program, launched by the National Institutes of Health, is an ambitious effort to gather data for over a million people living in the U.S. It will likely accelerate precision medicine research with the goal of eventually benefiting everyone by providing information that healthcare providers can use in the clinic. However, there are aspects of precision medicine that have emerged, or are beginning to emerge, in different clinics across the country and are being used to benefit patients today.

Pharmacogenomics (PGx), the study of genetic variations that cause individuals to respond differently to medications, is the most widely used form of precision medicine today. Virtually all of us harbor at least one genetic change that predisposes us to metabolize a common medication differently than the average person. A PGx panel with multiple genes can provide gene-drug guidelines for dozens of medications, including common ones like Warfarin, Clopidogrel or various antidepressants.

In addition to government initiatives, PGx and precision medicine is being fueled by the decreasing cost of genomic testing and growing consumer interest in it. More than 50% of adults are interested in genetic testing, and 6% indicate that they have already undergone it, according to patient surveys[1].

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Where is precision medicine headed? - ModernMedicine

July 18, 2017

Researchers at University of Massachusetts Medical School and Auburn University College of Veterinary Medicine are nearing human clinical trials on a genetic therapy for two rare neurological diseases that are fatal to children.

The scientists are seeking approval from the U.S. Food and Drug Administration (FDA), to test a gene therapy treatment for Tay-Sachs and Sandhoff diseases, genetic disorders in a category known as lysosomal storage diseases.

Tay-Sachs and Sandhoff are inherited neurologic diseases that occur when genetic mutations prevent cells from producing enzymes needed to break down and recycle materials. Without these enzymes, the materials accumulate to toxic levels, slowly destroying the nervous system. The researchers are working on a gene therapy to correct the enzyme deficiency using adeno-associated virus, or AAV, vectors.

The average life expectancy for children with infantile Tay-Sachs or Sandhoff disease is only 3 to 5 years. There is currently no treatment. The gene therapy in development has shown promise in animal models of these diseases by extending lifespans by up to four times those of untreated animals.

"The proof-of-concept studies in affected animals are compelling, and the FDA provided a clear path of remaining experiments needed to seek approval for human clinical trials," said Douglas R. Martin, a professor at Auburn University's College of Veterinary Medicine. "We now need the funding to complete the studies."

The animal phase of toxicity studies necessary to demonstrate the safety of the gene therapy for Tay-Sachs and Sandhoff diseases has been completed with the support of the National Tay-Sachs & Allied Disease Association and the Cure Tay-Sachs Foundation.

"Too many children with Tay-Sachs and Sandhoff have died since we started this project. The time has finally arrived to push back on these diseases," says Miguel Sena-Esteves, PhD, associate professor of neurology at UMass Medical School. "Our single-minded goal is to get a safe and potentially effective therapy to patients and their families as quickly as possible."

"Hopefully, once the news gets out that we are this close to human clinical trials, fundraising efforts will be sufficient so we can complete the IND-enabling studies and proceed to human clinical trials," said veterinarian Heather Gray-Edwards, an assistant professor at Auburn University College of Veterinary Medicine.

Additional funding of $1.2 million is being sought to complete the safety studies, fund the production of clinical grade AAV, and complete regulatory filings.

Explore further: Promising results with new gene therapy approach for treating inherited neurodegenerative diseases

Transplantation of therapeutic stem cells directly into the central nervous system (CNS) is a promising new approach to treating the neurological effects of lysosomal storage diseases (LSD), a group of at least 50 different ...

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Promising therapy for fatal genetic diseases in children nears human trials - Medical Xpress

July 18, 2017 Credit: CC0 Public Domain

Researchers funded by the Swiss National Science Foundation (SNSF) have discovered mutations that worsen respiratory infections among children. Their study explain the mechanism involved.

Colds that are not linked to influenza are generally benign. Still, 2 percent of each generation of children have to go to hospital following a virulent infection. "These respiratory problems are responsible for 20 percent of child mortality around the world", says Jacques Fellay, who has held an SNSF professorship since 2011. "It is truly a silent epidemic."

An international research collaboration coordinated by Fellay has discovered the reason for some of these infections: they are caused by mutations of a gene that plays a part in recognising certain cold-inducing viruses.

"We have been able to confirm that a gene, called IFIH1, plays an important role in defending the body against the principal viruses responsible for respiratory infections among children", he explains. This gene normally helps in identifying the virus's RNA, a type of genetic information related to the DNA. "We have been able to isolate the mechanisms that prevent the immune systems of children with an IFIH mutation from successfully combating the viral infection."

Hospitals in Switzerland and Australia

The researchers collaborated with various paediatric wards in Swiss and Australian hospitals to study cases of children who needed intensive care after a severe respiratory infection (bronchiolitis or pneumonia) caused by a virus. They excluded premature babies and children with chronic illnesses in order to focus on the genetic causes. The result: of the 120 children included in the study, eight carried mutations of the IFIH1 gene.

"This gene encodes a protein which recognises the presence of a certain number of cold-inducing microbes in a cell, such as the respiratory syncytial virus (RSV) or rhinoviruses", explains Samira Asgari of EPFL, who designed the experiments. "They attach themselves to the germ's RNA and trigger a cascade of molecular signals that provoke an effective immune reaction." The researcher has been able to show that three different mutations of IFIH1 render the protein incapable of recognising the virus, thereby preventing the body from defending itself against the infection.

In 2015, Jacques Fellay had already studied the genome of more than 2000 patients and statistically shown which genetic variations influence our capacity to defend ourselves against common viral infections. "The two approaches are complementary", says Fellay. "A study covering a large number of subjects, like the one in 2015, makes it possible to identify the relevant genes across the entire population; but their variations have only a limited impact on individuals. In contrast, a study focusing on carefully selected patients enables you to investigate mutations that are more rare but also more critical for the patient, and to pinpoint the mechanisms in play."

Prevention and therapy

These results should prove useful for setting new therapeutic and preventive targets: "At their parents' request, we also tested the siblings of some of the children carrying the mutation to see if they too are more fragile when it comes to infections. If this is the case, parents may decide to keep their child at home during an epidemic, or to go to hospital double-quick if the child catches a cold."

For Jacques Fellay, this research work aptly illustrates the methods and objectives of personalised medicine or 'precision medicine': "Our bodies' capacity to ward off illnesses can vary greatly. A better understanding of the genetic mechanisms that create these differences will lead to more targeted prevention and therapy. One scenario might involve genetic screening to determine the degree of susceptibility to infections; this could be included in the blood tests that are routinely performed just after birth. But society would need to have a say in deciding which genetic tests are desirable."

Explore further: Genetic immune deficiency could hold key to severe childhood infections

More information: Samira Asgari et al. Severe viral respiratory infections in children with IFIH1 loss-of-function mutations, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1704259114

Christian Hammer et al. Amino Acid Variation in HLA Class II Proteins Is a Major Determinant of Humoral Response to Common Viruses, The American Journal of Human Genetics (2015). DOI: 10.1016/j.ajhg.2015.09.008

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Gene increases the severity of common colds - Phys.Org

When Audrey Lapidus 10-month old son, Calvin, didnt reach normal milestones like rolling over or crawling, she knew something was wrong.

He was certainly different from our first child, said Lapidus, of Los Angeles. He had a lot of gastrointestinal issues and we were taking him to the doctor quite a bit.

Four specialists saw Calvin and batteries of tests proved inconclusive. Still, Lapidus persisted.

I was pushing for even more testing, and our geneticist at UCLA said, If you can wait one more month, were going to be launching a brand new test called exome sequencing, she said. We were lucky to be in the right place at the right time and get the information we did.

In 2012, Calvin Lapidus became the first patient to undergo exome sequencing at UCLA. He was subsequently diagnosed with a rare genetic condition known as Pitt-Hopkins syndrome, which is most commonly characterized by developmental delays, possible breathing problems, seizures and gastrointestinal problems.

Though there is no cure for Pitt-Hopkins, finally having a diagnosis allowed Calvin to begin therapy. The diagnosis gave us a point to move forward from, rather than just existing in that scary no-mans land where we knew nothing, Lapidus said.

Unfortunately, there are a lot of people living in that no-mans land, desperate for any type of answers to their medical conditions, saidDr. Stanley Nelson, professor of human genetics and pathology and laboratory medicine atthe David Geffen School of Medicine at UCLA. Many families suffer for years without so much as a name for their condition.

What exome sequencing allows doctors to do is to analyze more than 20,000 genes at once, with one simple blood test.

In the past, genetic testing was done one gene at a time, which is time-consuming and expensive.

Rather than testing one sequential gene after another, exome sequencing saves time, money and effort, saidDr. Julian Martinez-Agosto, a pediatrician and researcher at theResnick Neuropsychiatric Hospital at UCLA.

The exome consists of all the genomes exons, which are the coding portion of genes. Clinical exome sequencing is a test for identifying disease-causing DNA variants within the 1 percent of the genome which codes for proteins, the exons, or flanks the regions which code for proteins.

To date, mutations in the protein-coding parts of genes accounts for nearly 85 percent of all mutations known to cause genetic diseases, so surveying just this portion of the genome is an efficient and powerful diagnostic tool. Exome sequencing can help detect rare disorders like spinocerebellar ataxia, which progressively diminishes a persons movements, and suggest the likelihood of more common conditions like autism spectrum disorder and epilepsy.

More than 4,000 adults and children have undergone exome testing at UCLA since 2012. Of difficult to solve cases, more than 30 percent are solved through this process, which is a dramatic improvement over prior technologies.Thus, Nelson and his team support wider use of genome-sequencing techniques and better insurance coverage, which would further benefit patients and resolve diagnostically difficult cases at much younger ages.

Since her sons diagnosis, Lapidus helped found the Pitt-Hopkins Syndrome Research Foundation. Having Calvins diagnosis gave us a roadmap of where to start, where to go and whats realistic as far as therapies and treatments, she said. None of that would have been possible without that test.

Next, experts at UCLA are testing the relative merits of broader whole genome sequencing to analyze all6 billionbases that make up a persons genome.The team is exploring integration of this DNA sequencing with state-of-the-art RNA or gene expression analysis to improve the diagnostic rate.

The entire human genome was first sequenced in 1990 at a cost of $2.7 billion. Today, doctors can perform the same test at a tiny fraction of that cost, and believe that sequencing whole genomes of individuals could vastly improve disease diagnoses and medical care.

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Genetic sequencing unravels rare disease mysteries - UCLA Newsroom