A small number of people who are infected with HIV-1 produce very special antibodies. These antibodies do not just fight one virus strain, but neutralize almost all known virus strains. Research into developing an HIV vaccine focuses on discovering the factors responsible for the production of such antibodies.
A Swiss research team led by the University of Zurich (UZH) and University Hospital Zurich (USZ) has been searching for these factors for years. Several have already been identified: For example, the virus load and the diversity of the viruses, the duration of the infection, and the ethnicity of the affected person can all influence the body’s immune response. "In our new study, we were able to identify another factor: The genome of the HI virus," says Huldrych Günthard, deputy director of the Department of Infectious Diseases and Hospital Epidemiology at USZ.
The starting point for the researchers was the data and biobanked blood samples of around 4,500 HIV-infected people, recorded in the Swiss HIV Cohort Study and the Zurich Primary HIV Infection Study. In total the researchers found 303 potential transmission pairs – i.e. pairs of patients for whom the similarity of the viruses’ genomic RNA indicated that they were probably infected with the same virus strain. "By comparing the immune response of these pairs of patients, we were able to show that the HI virus itself has an influence on the extent and specificity of the antibody reactions," explains the study’s first author Roger Kouyos, research group leader at the Department of Infectious Diseases and Hospital Epidemiology at USZ.
Antibodies acting against HIV bind to proteins found on the surface of the virus. These envelope proteins differ according to virus strain and subtype. The researchers therefore examined more closely a patient pair with very similar virus genomes and at the same time very strong activity of broadly neutralizing antibodies. "We discovered that there must be a special envelope protein that causes an efficient defense," explains Alexandra Trkola, virologist and head of the Institute of Medical Virology at UZH.
In order to be able to develop an effective vaccine against HIV-1, it is necessary to pinpoint the envelope proteins and virus strains that lead to the formation of broadly acting antibodies. It is therefore planned to widen the search. "We have found one candidate. Based on that, we now want to begin developing an immunogen ourselves," adds Trkola.
https://www.eurekalert.org

The largest study of its kind, led by international researchers including scientists at RCSI (Royal College of Surgeons in Ireland), has discovered 11 new genes associated with epilepsy.
The research is published in today’s issue of Nature Communications (DOI: 10.1038/s41467-018-07524-z). It greatly advances knowledge of the underlying biological causes of epilepsy and may inform the development of new treatments for the condition.
Researchers compared the DNA of more than 15,000 people with epilepsy to the DNA of 30,000 people without epilepsy. This has created a better understanding of genetic factors that contribute to the most common forms of this condition, and the results tripled the number of known genetic associations for epilepsy and implicated 11 new genes.
The researchers found that the majority of current anti-epileptic drugs directly target one or more of the associated genes and identified an additional 166 drugs that do the same. These drugs are promising new candidates for epilepsy therapy as they directly target the genetic basis of the disease.
“This work illustrates the power of scientists collaborating across countries and continents. Discovering these new genes for epilepsy provides important information towards novel treatments for the condition. This is another important step on the road towards curing the epilepsies,” said Gianpiero Cavalleri, Associate Professor at the RCSI Department of Molecular and Cellular Therapeutics and Deputy Director of the FutureNeuro SFI Research Centre.
"In addition to the biological insights provided by the findings, this study will encourage researchers to develop personalised and precision therapies for patients with difficult and complex epilepsy. This will provide better seizure control and will enable improved quality of life for patients and families," said consultant neurologist Norman Delanty, Associate Professor at RCSI, FutureNeuro and Beaumont Hospital.
“We have appreciated for some time that genetics plays an important role in epilepsy, however, until now, relatively little was known about the specific genes responsible for the most common forms of the disorder.  Identifying the genes that cause epilepsy is particularly important when we consider that a third of the 65 million patients worldwide will not become seizure free using current treatment options,” said Dr Colin Doherty, National Clinical Lead for Epilepsy and a Principal Investigator at the FutureNeuro Centre.
Over 150 researchers, based across Europe, Australia, Asia, South America and North America, carried out the research.  They worked together as part of the International League Against Epilepsy (ILAE) Consortium on Complex Epilepsies. The ILAE Consortium was formed by researchers in 2010, recognising that the complexity of genetic and environmental factors underlying epilepsy would require research across massive datasets, and therefore unprecedented collaboration on an international scale. Science Foundation Ireland (SFI) part-funded the study.
“Conducting a study of this size and scope is an incredible accomplishment that RCSI and FutureNeuro were delighted to help lead.  We look forward to building on the results of this study and strengthening international collaborations,” said Professor Cavalleri.
“The next steps would be expanding these results in an even larger sample, which is underway, and then drilling down on specific groups of patients and the genes that influence their type of epilepsy to trial new therapies,” Professor Sam Berkovic, University of Melbourne.

A new study, led by Professor Elina Hyppönen from UniSA’s Australian Centre for Precision Health, presents the strongest evidence yet of a causal relationship between obesity and a wide range of serious conditions, including cardiovascular disease, diabetes, cancer, and neurological, musculoskeletal and respiratory afflictions.
The study draws data from the UK Biobank – a research database holding health and genetic information from half a million volunteers – to analyse associations between body mass index (BMI) and a range of disease outcomes in 337,536 people.
“In this study we used a genetic approach to seek evidence for true health effects associated with higher body mass index, which assesses our weight against our height and is commonly used to measure obesity,” Prof Hyppönen says.
Previous research has suggested that high BMI is associated with increased risk of chronic diseases such as type 2 diabetes, cardiovascular disease and cancer, but due to the difficulty of conducting clinical trials related to obesity, it has been hard to prove causation.
Prof Hyppönen and her team developed a multi-dimensional analysis in which genetic data was subjected to a suite of stringent examinations in order to deliver high confidence of causality.
“We compared evidence from five different statistical approaches to establish how strong the evidence for causal effect actually is,” she says.
“Fully consistent evidence across all approaches was seen for 14 different diseases, and for 26 different diseases evidence was obtained by at least for four of the five methods used.
“What increases the confidence that these associations are largely reflective of real effects is the fact that those effects which came across with consistent evidence are also ones for which we have previous clinical evidence.”
One key finding from the study was the extent to which it confirms existing concerns over the link between obesity and diabetes, with many of the diseases identified as related to high BMI known to be commonly associated with poorly controlled diabetes.
“For example, we saw evidence for effects on peripheral nerve disorders, chronic leg and foot ulcers, and even gangrene and kidney failure, which are all known to be diabetic complications. This suggests a key aspect to reduce comorbidity risk in obesity is careful monitoring of blood sugar and effective control of diabetes and its complications,” Prof Hyppönen says.
The study also highlights the importance of genetic research to further our understanding of the role genes play in obesity, and the insights it can provide for the future management and treatment of obesity.
University of South Australia https://tinyurl.com/yxmrpkm5

Scientists have discovered that some childhood bone cancers start growing years before they are currently diagnosed. Researchers at the Wellcome Sanger Institute and Hospital for Sick Children (SickKids), Canada discovered large-scale genetic rearrangements in Ewing Sarcomas and other children’s cancers, and showed these can take years to form in bone or soft tissue. This study will help unravel the causes of childhood cancers and raises the possibility of finding ways to diagnose and treat these cancers earlier in the future.
The research also showed that cancers with the complex genetic rearrangements were more aggressive and could benefit from more intense treatment than other cancers. This will help doctors decide on the best treatment for each patient.
Ewing sarcoma is a rare cancer found mainly in bone or soft tissue of young teenagers as they grow, and is the second most commonly diagnosed bone cancer in children and young people. Treatment involves chemotherapy, surgery to remove the affected part of the bone if possible and radiotherapy. However, this harsh regime has hardly changed for the last 40 years and fails about one third of patients.
Cancer is a genetic disease and in Ewing sarcoma, two specific genes, EWSR1 and ETS, are fused together. To understand the genetic events leading to this, researchers sequenced and analysed the genomes of 124 tumours. They discovered that in nearly half of the cases, the main gene fusion occurred when the DNA completely rearranged itself, forming complex loops of DNA.
“Many childhood sarcomas are driven by gene fusions, however until now we have not known how or when these key events occur, or whether these processes change at relapse. We found dramatic early chromosomal shattering in 42 per cent of Ewing sarcomas, not only fusing two critical genes together, but also disrupting a number of important areas.”
Dr Adam Shlien, one of the lead authors on the paper, Associate Director of Translational Genetics and Scientist in Genetics & Genome Biology, and co-Director of the SickKids Cancer Sequencing (KiCS) program at SickKids
The earlier a cancer is diagnosed, the easier it is to treat, but until now it was thought that Ewing sarcoma was very fast growing. Surprisingly, the researchers found that the complex DNA rearrangements that cause Ewing sarcoma had occurred years before the tumour was diagnosed. This offers possibilities of finding ways to screen for these cancers to treat them earlier.
“In principle this study provides evidence that Ewing sarcoma could be detectable earlier, possibly even before it reveals itself as disease. If we could detect these childhood cancers sooner, when tumours are smaller, they would be much easier to treat. Further research is needed, but this possibility of finding a way to diagnose Ewing sarcomas earlier could help patients in the future.”

Wellcome Sanger Institute
www.sanger.ac.uk/news/view/children-s-bone-cancers-could-remain-hidden-years-diagnosis

Messe Düsseldorf will participate in the AACC Clinical Lab Expo 2019 in order to promote its “MEDICAlliance” program of regional and international medical trade fairs organized around the globe.  At AACC booth 2653, visitor and exhibitor information for MEDICA 2019, World Forum for Medicine, and COMPAMED 2019, High tech solutions for medical technology (held currently from November 18 – 21, 2019 in Düsseldorf, Germany), MEDICAL FAIR CHINA 2019 (September 5 – 7, 2019 in Suzou), MEDICAL FAIR THAILAND 2019 (September 11 – 13, 2019 in Bangkok) as well as MEDICAL FAIR ASIA 2020 and MEDICAL MANUFACTURING ASIA 2020 (held concurrently from September 9 – 11, 2020 in Singapore) and Meditech 2020 (July 14 – 17, 2020 in Bogota, Colombia) will be available.
As the No. 1 international medical trade fair worldwide, MEDICA reflects the status of the medical market. Every year, over 5,200 exhibitors from 66 nations present the complete range of new products, systems and services for high-quality in-patient and out-patient care to about 120,000 visitors from around the globe. Over 70% of the MEDICA exhibitors usually come from nations other than Germany, including more than 400 companies from the U.S. As in the past, Messe Düsseldorf North America will again organize two U.S. Pavilions at MEDICA 2019. Congresses, various theme parks, forums and numerous special events will complement the exhibits. www.medicalliance.global www.medica-tradefair.com