Mathilde came into the world with chubby cheeks and a full head of auburn hair. But she was a very sick baby, and was immediately transferred on January 19, 2013 to the Neonatal Intensive Care Unit at the Montreal Children’s Hospital of the McGill University Health Centre (MCH-MUHC). By the time she arrived, she was sicker than initially expected; Mathilde’s small head was of particular concern to doctors. She underwent neurological tests, and sadly, they came back abnormal: her brain hadn’t developed properly and her brain white matter (or myelin) was found to be atypical. Doctors confirmed she was suffering from an unidentified kind of genetic leukoencephalopathy, a family of diseases affecting both the nerve cells and the white matter. Mathilde passed away when she was two-and-a-half months old, surrounded by the people who loved her most.
Thanks to an international effort led by physician-scientists at Rady Children’s Institute for Genomic Medicine (RCIGM)-San Diego in California, Dr. Geneviève Bernard’s team at the Research Institute of the McGill University Health Centre (RI-MUHC) was able to confirm the diagnosis for Mathilde: she died from VARS-related disorder, an extremely rare neurodevelopmental condition. Their findings are paving the way for the first step in developing potential therapies for this rare neurodegenerative condition.
Investigators performed advanced genetic tests on blood samples from seven children with neuro-developmental disabilities who were evaluated by doctors in San Diego, Montreal and Cairo. This led to the discovery of mutations in the VARS gene, which had not previously been linked to human disease.
“These children showed epileptic seizures and abnormalities evident on brain MRI scans,” said lead study’s author Joseph Gleeson, MD, director of neurodevelopmental genetics at RCIGM and professor of neuroscience and pediatrics at UC San Diego School of Medicine. “Although no treatment currently exists for this condition, the results are important as the first step in guiding research directed at targeted therapies.”
The genetic mutations identified in the study led to a defect in the enzyme responsible for generating proteins containing the amino acid valine, which is necessary for cellular health. Genetic variations that damage these types of enzymes are associated with a variety of human diseases including microcephaly and neuropathy.
In this study, the team found that enzymatic activity was significantly reduced in cells from their young patients. The findings suggest that children with this disorder may benefit from treatments to support the synthesis of new valine-containing proteins in the brain.

McGill University Health Centrehttps://tinyurl.com/yxjg3dp5

Some variations in the gene LPHN3 –associated with the attention deficit / hyperactivity disorder (ADHD) in kids and adults- could favour likelihood to smoke, consume alcohol, cannabis and other addictive substances, according to an article.
The findings are based on the study of around 2,700 patients –children, adolescents and adults- from the United States, Colombia and Spain, and it will contribute to provide new genetic tools to improve prevention of addictive behaviours in people with ADHD.
ADHD is one of the most commons disorders in childhood and adolescence –it can linger until adulthood- and its traits are hyperactivity, impulsiveness, and attention deficit. One of the genes related to ADHD susceptibility is LPHN3, which codes the protein latrophilin 3, “a molecule related to the formation of synaptic connections between certain types of neurons, and therefore, a good candidate to set a relation with any psychiatric disorder”, notes the lecturer Bru Cormand, head of the Research Group on Neurogenetics of the Faculty of Biology of the UB.
The connection between LPHN3 and ADHD is one of the most studied regarding the etiology of the disorder. This gene, in addition, has an impact on the patients’ response to the medication, the degree of severity of the disease and disruptive behaviour. However, so far, the depth of the relation between the gene LPHN3 and substance addiction had not been explored.
In the new study, the experts applied an innovative statistical method (Recursive-partitioning Frameworks) which integrates clinical, demographic and genetic information on a specific disorder –in this case, ADHD- to predict another co-morbid disorder (which appears concurringly), such as addiction to tobacco, alcohol, cocaine, cannabis and marijuana, among others.
Conclusions note that, within the group of Spanish patients with ADHD, a specific variation of the LPHN3 gene increases by 40 % the risk of nicotine dependence. According to the experts, results are similar in the cases for alcohol and illegal drugs, which have been studied together in the research.
Not all those affected by ADHD show behaviours with an addictive profile over their lives. “We now know genetics play an important role in these behaviours. This helps us to prevent future risks in kids and adults with ADHD and to improve prevention strategies. However, ADHD genetics are diverse, there are many involved genes and these vary among the patients with the disorder”, notes Cormand.
75 % of ADHD has a genetic base and the remaining 25 % is related to environmental factors which can vary, according to the experts. Therefore, external factors can be relevant in the appearance of addictive behaviours in people with ADHD. For example, certain lifestyles or social interactions can play an important role.
“Also, cocaine and other addictive substances –warns Cormand- have a psychostimulant action similar to the one in the main pharmacological treatment for ADHD. This would explain why, in some cases, these are used by the affected people as self-medication for its apparently ‘beneficial’ effects”.
Psychological and pharmacological treatment and psychopedagogical intervention are the combined strategies that are most efficient in ADHD treatment. In the future, we will need new clinical studies to analyse the importance of genetics in ADHD susceptibility and addictive behaviours that can affect the patient’s health.

University of Barcelonahttps://tinyurl.com/y5qzsvv6

Nova Biomedical has been awarded a multi-year group purchasing agreement for critical care blood gas analysers from Premier. This agreement provides Premier members access to Nova’s new Stat Profile Prime Plus® critical care blood gas analyser. Prime Plus features maintenance-free sensor technology to provide 20 essential critical care tests including BUN, creatinine, ionized magnesium, blood gases, electrolytes, metabolites, hematology, and co-oximetry. Prime Plus also provides new and patented, non-lysing whole blood co-oximetry technology, along with automated quality control (QC), powerful data management, bidirectional connectivity, and extensive cybersecurity protection. The current agreement allows Premier members, at their discretion, to take advantage of special, pre-negotiated pricing and terms for Prime Plus analysers and consumables in addition to Nova’s 10-test Prime analysers.
“We are pleased that Premier has awarded a group purchasing agreement to our innovative, maintenance-free Prime Plus,” said John Britt, Director of Corporate Accounts for Nova. “This agreement allows Premier members access to the entire Stat Profile Prime platform including its new flagship analyser, Prime Plus. Prime Plus introduces innovative technology that expands critical care testing with unique assays and eliminates sensor and co-oximeter maintenance, all of which improves uptime and reliability while reducing costs. Prime Plus represents the latest in critical care testing technology and further demonstrates Nova’s leadership and history of innovation.”
Prime Plus incorporates Nova’s innovative, maintenance-free sensor technology with individual MicroSensor cards, calibrator cartridges, and quality control cartridges. This design eliminates sensor and co-oximeter maintenance, improves analyser uptime, and reduces testing costs for the compact and easy-to-use Prime Plus.
Premier is a leading healthcare improvement company, uniting an alliance of approximately 4,000 U.S. hospitals and 165,000 other providers.
www.novabiomedical.com

Scientists have discovered a new gene variation that causes motor neurone disease (MND) in a novel biological pathway that until now hasn’t been linked with neurodegeneration.
The findings for the pioneering study, conducted by a team of researchers from the Sheffield Institute for Translational Neuroscience (SITraN) and the NIHR Sheffield Biomedical Research Centre (BRC), could potentially help to identify completely new ways of treating MND which currently affects over 5,000 people in the UK.
MND, also known as Amyotrophic Lateral Sclerosis (ALS), is a devastating neurodegenerative disorder that affects the nerves – motor neurones – that form the connection between the brain and the muscles. The messages from these nerves gradually stop reaching the muscles, causing them to weaken, stiffen and eventually waste. The progressive disease affects a person’s ability to walk, talk, eat and breathe. Approximately 10 per cent of MND cases are inherited but the remaining 90 per cent are caused by complex genetic and environmental interactions which are not well understood – this is known as sporadic MND. There is currently no curative therapy.

Dr Johnathan Cooper-Knock, NIHR Clinical Lecturer at the University of Sheffield’s Institute for Translational Neuroscience (SITraN), explained the impact of the ground-breaking research which is helping scientists to understand the fundamental genetic basis of MND.
“This new gene does not fit into a biological function that we already know is associated with MND,” said Dr Cooper-Knock.
“That means that this finding has potential to identify completely new ways of treating MND.
“The mutations found in patients were shown to be toxic to neurons and, when expressed in zebrafish they produced muscle weakness consistent with MND. This work strongly suggests that the mutations are the cause of MND in the patients where they were identified.”
During the study, researchers genetically sequenced tissue from two related patients with an unknown familial form of MND and found a mutation in the substrate binding region of a glycosyltransferase enzyme called GLT8D1. They went on to screen a larger sample of 103 patients, five of whom had this mutation. The study revealed a new genetic subtype of MND.

University of Sheffieldhttps://tinyurl.com/y4bwpra4

Researchers at the School of Medicine have identified an unexpected contributor to rheumatoid arthritis that may help explain the painful flare-ups associated with the disease. The discovery points to a potential new treatment for the autoimmune disorder and may also allow the use of a simple blood test to detect people at elevated risk for developing the condition.
The arthritis discovery originated in the lab of UVA’s Kodi Ravichandran, PhD, and was facilitated by combining his team’s resources and expertise with that of Inova researcher Thomas Conrads, PhD, through a THRIV UVA-Inova seed grant.
The new findings about rheumatoid arthritis came in an unexpected fashion. Sanja Arandjelovic, PhD, a research scientist in the Ravichandran group, was seeking to better understand what causes the inflammation associated with inflammatory arthritis when she noted that deleting a gene called ELMO1 alleviated arthritis symptoms in mice. This was particularly surprising because Arandjelovic and Ravichandran initially thought that loss of ELMO1 would result in increased inflammation.
“This was a complete surprise to us initially,” recalled Ravichandran, chairman of UVA’s Department of Microbiology, Immunology and Cancer Biology. “I love those kinds of results, because they tell us that, first, we did not fully comprehend the scientific problem when we began exploring it, and, second, such unexpected results challenge us to think in a different way. Given that rheumatoid arthritis affects millions of people worldwide, we felt the need to understand this observation better.”
Digging deeper into the unusual outcome, the researchers determined that ELMO1 promotes inflammation via their function in white blood cells called neutrophils. Ravichandran described neutrophils as the body’s “first line of defence” because they sense and respond to potential threats. “Normally they are good for us, against many bacterial infections,” he said. “But also there are many times when they produce a lot of friendly fire that is quite damaging to the tissues – when they hang around too long or there are too many neutrophils coming in – in this case, infiltrating into the joints during arthritis.”
The researchers also discovered that there is a natural variation in the ELMO1 gene that can prompt neutrophils to become more mobile and have the potential to invade the joints in greater numbers and induce inflammation. (The potential blood test would detect this variation.)
Here things take a particularly cool turn: Normally, doctors are reluctant to try to block the effect of genes like ELMO1 in people, because such genes can play diverse roles in the body. But Ravichandran believes that ELMO1 is different. “ELMO1 partners with very specific set of proteins only in the neutrophils but not in other cells types we tested,” he said. “So, presumably, you may be able to affect only a select cell type.” This latter result came about from a collaborative study where Conrads’ group at Inova performed sophisticated analysis of ELMO1 proteomic partners in neutrophils, many of which also have previously known links to human arthritis. This provided further validation for the role of ELMO1 in rheumatoid arthritis.
Encouragingly, blocking ELMO1 in lab mice alleviated arthritis inflammation without causing other problems, Ravichandran noted. His laboratory is now seeking to identify drugs that could inhibit the function of ELMO1 and is also designing a test for the variation (also called polymorphism) in the ELMO1 gene.
“This is another example of how fundamental basic research can lead to novel discoveries on clinically relevant problems that affect a large number of people,” Ravichandran said.

University of Virginia
newsroom.uvahealth.com/2019/02/07/surprise-rheumatoid-arthritis-discovery-points-to-new-treatment/