The Wellcome-funded diagnostic – developed by researchers at University College London (UCL) and the Western Eye Hospital – allows doctors to see individual nerve cell death in the back of the eye.
Early detection means doctors can start treatment before sight loss begins. The test also has potential for early diagnosis of other degenerative neurological conditions, including Parkinson’s, Alzheimer’s and multiple sclerosis.
Professor Francesca Cordeiro, at UCL Institute of Opthamology, who led the research, said: "Although detection has been improving, most patients have lost a third of vision by the time they are diagnosed.
"Now, for the first time, we have been able to show individual cell death and detect the earliest signs of glaucoma. While we cannot cure the disease, our test means treatment can start before symptoms begin."
Glaucoma affects 60 million people worldwide and one in ten go blind.
The new technique means patients could be diagnosed up to ten years earlier than is currently possible.
Bethan Hughes, Wellcome’s Strategic Development Lead for Innovation, said: "This innovation has the potential to transform lives for those who suffer loss of sight through glaucoma, and offers hope of a breakthrough in early diagnosis of other neurodegenerative diseases."
Loss of sight in patients with glaucoma is caused by the death of cells in the retina at the back of the eye – apoptosis.
The new technique is called DARC, which stands for detection of apoptosing retinal cells.
It uses a specially developed fluorescent marker which attaches to cell proteins when it’s injected into patients. Damaged retinal cells appear as white fluorescent spots during eye examination.
Initial clinical trials were carried out on a small number of glaucoma patients and compared with tests on healthy people to establish the test’s safety.
DARC uses equipment that is already part of routine hospital eye examinations.
The researchers hope that eventually it may be possible for opticians to do the tests. This would mean even earlier detection of the disease.
Treatment for glaucoma is much more successful when it is begun in the early stages of the disease.
Further studies will now be carried out into DARC and how it could be used to detect other neurodegenerative conditions where increasing numbers of nerve cells are lost as the disease progresses.

Wellcome Trust
wellcome.ac.uk/news/new-eye-test-detects-earliest-signs-glaucoma

The scientists from the Montreal Neurological Institute and Hospital at McGill University, led by Peter McPherson, along with collaborators in Saudi Arabia, Jordan, Germany, and at SickKids Hospital and the University of Toronto, have discovered that a severe form of epileptic encephalopathy is caused by recessive loss-of-function mutations in the gene DENND5A.
Epileptic encephalopathy is a rare but devastating sub-form of epilepsy that results in severe mental and physical disabilities in children from birth. It is often caused by improper development of the brain. Individuals with epileptic encephalopathy caused by mutations in DENND5A present with serious anomalies in brain structure along with calcifications in the brain and altered facial features.
Researchers performed whole exome sequencing on three children with epileptic encephalopathy from two families, one from Saudi Arabia and another from Jordan. Both families were consanguineous, meaning the parents were related to each other. This greatly increases the chance that rare mutations that are recessive and that cause no harm to the parents are expressed in the children. The whole exome sequencing, along with extensive and complex genetic analysis, revealed that recessive mutations in DENND5A were responsible for the disease, with the Saudi family and the Jordanian family having different mutations but in the same DENND5A gene. They found that mutations in DENND5A lead to a lack of the DENND5A protein, resulting in underdevelopment of the central nervous system. The protein expressed from the DENND5A gene is present at highest levels in the nervous system especially while the brain is developing, corroborating the evidence that mutations in the gene cause epileptic encephalopathy.
The researchers discovered that the DENND5A protein controls the movement of receptors for key developmental factors called neurotrophins. Disruption of DENND5A function leads to altered levels of these receptors, which could explain why loss of DENND5A leads to the severe neurological developmental defects in the patients.
Epilepsy affects approximately three per cent of the world population, and epileptic encephalopathy is a rare sub-form of the disease. It is difficult to say how many children with epileptic encephalopathy have the DENND5A mutations, but now that the gene has been identified as a cause, researchers around the world can begin to test patients for mutations in this gene.
This finding also improves our understanding of neuronal development. The observation that loss-of-function mutations in DENND5A causes epileptic encephalopathy suggests that DENND5A protein controls membrane trafficking pathways critical for normal neuronal development and strengthens the argument that protein trafficking processes in cells are critical for normal neuronal development and function.
“Our study demonstrates the importance of membrane trafficking in neuronal development and it provides a new pathophysiological mechanism for this disease type. This will allow physicians around the world to test if mutations in DENND5A are causing the disease in their patients, and also to provide genetic counselling for affected families,” says Dr. Chanshuai Han, the lead author on the study.

The Montreal Neurological Institute and Hospital http://tinyurl.com/jfb7aho

Massachusetts General Hospital (MGH) researchers have identified a mechanism that controls the expression of genes regulating the growth of the most aggressive form of medulloblastoma, the most common paediatric brain tumour. The team also identifies potential targets for future treatments.

“We set out to find the most important regulators of gene expression programs in medulloblastoma,” says senior author Miguel Rivera, MD, of the MGH Department of Pathology and the Center for Cancer Research. “To do that we used a powerful genomic technology called chromatin profiling to map all the genomic elements contributing to transcription regulation in Group 3 medulloblastoma – the most aggressive subtype. This goes beyond measuring gene expression because it tells you how genes are turned on and off.”

Medulloblastoma is a fast-growing tumour that arises in the developing brain and most commonly affects children under the age of 10. Four molecular variants, each with different patterns of DNA alteration and gene expression, have been identified. Subtypes WNT and SSH are the best understood; the other two – Group 3 and Group 4 – are poorly understood and account for 60 percent of tumours.

Cells regulate whether specific genes are transcribed into RNA through the action of transcription factors, proteins that bind to DNA and either stimulate or suppress the expression of their target genes. Rivera’s team used advanced genomic technologies to identify key DNA elements called enhancers that were active in primary Group 3 medulloblastoma samples and cell lines. The transcription factor OTX2, which plays a role in normal brain development and is known to be highly expressed in Group 3 medulloblastomas, was present at the majority of active enhancer sites in tumours, suggesting it may have a role in promoting the expression of tumour-associated genes.

Subsequent experiments revealed that OTX2 can function as a “pioneer factor,” opening up chromatin – which consists of DNA wound around proteins called histones – to activate enhancers and that its function is amplified by a second transcription factor called NEUROD1. The investigators then identified a set of genes the expression of which was significantly reduced when OTX2 was suppressed. Among these genes, they found that expression of the kinase NEK2 responded to OTX2 levels and that its depletion or pharmacologic inhibition strongly reduced the growth and survival of medulloblastoma cells.

“Overall, our findings show that OTX2 is a critical factor in regulating gene expression programs in Group 3 medulloblastoma and possibly in the WNT and Group 4 subtypes, where it is also expressed,” says Rivera, who is an assistant professor of Pathology at Harvard Medical School. “This work points to OTX2 itself and its target genes – including NEK2 – as potential therapeutic targets. Disruption of the relationship between OTX2 and NEUROD1 may also be a potential treatment strategy.

Massachusetts General Hospitalwww.massgeneral.org/about/pressrelease.aspx?id=2063

More than 3,000 medical laboratory industry professionals expected to attend the launch edition of MEDLAB Europe at the Fira Gran Via in Barcelona, Spain. 

After many years of operating successful MEDLAB events around Africa, Asia and the Middle East, Informa Life Sciences Exhibitions has announced that the MEDLAB Series will be expanding its presence into Europe. Taking place at the Fira Gran Via in Barcelona, Spain, from 13-15 September 2017, more than 3,000 industry professionals are expected to attend Europe’s leading event for laboratory management and diagnosis.
With the European medical laboratory market expected to reach USD 15.5 billion (€ 14.2 billion) by 2024[1], a platform such as MEDLAB presents a huge opportunity for global laboratory industry leaders, including manufacturers, dealers and distributors, to make inroads into the European market. Housing international exhibitors and covering 2,000 sqm of exhibition space, MEDLAB Europe will give visitors from across the world an opportunity to access cutting-edge laboratory products, next-generation technology, innovative services and world-class educational content. 
According to Tom Coleman, Group Exhibition Director, MEDLAB Series: “The launch of MEDLAB Europe is in line with our global expansion strategy for our MEDLAB series of events. The increasing prevalence of chronic diseases, rising geriatric population coupled with the rising awareness towards early diagnosis, has positioned the European medical laboratory market as a critical market for manufacturers, services providers, and dealers and distributors from across the globe. MEDLAB Europe will generate substantial value for our customers and partners by driving further product innovation and deeper engagement in these specific markets.”

Over the three-day event, MEDLAB Europe will also offer a multi-disciplinary congress tackling current challenges and developments key to the European market, and leveraging the true potential of laboratory testing to dramatically improve patient outcomes across the continent.

The conference programme covers five main tracks including Point of Care Testing (POCT), Histopathology, Lab Management, Microbiology and Hematology. From new methods of effective lab management to the development of techniques in detecting diseases, the conferences will also review the expanding role of the laboratory medicine and discuss partnership between a clinician and a lab professional in providing delivery of care to every patient.
“The scientific programme at MEDLAB has been carefully designed in collaboration with some of the brightest minds in the medical laboratory industry in order to have a real impact on improving the health and wellbeing of patients across the region,” said Coleman.

¹ http://www.grandviewresearch.com/press-release/europe-in-vitro-diagnostics-ivd-market-analysis

www.medlabeurope.com