A person carrying variants of two particular genes could be almost three times more likely to develop multiple sclerosis, according to the latest findings from scientists at The University of Texas Medical Branch at Galveston and Duke University Medical Center.
One of these variants is in IL7R, a gene previously associated with MS, and the other in DDX39B, a gene not previously connected to the disease.
The discovery could open the way to the development of more accurate tests to identify those at greatest risk of MS, and possibly other autoimmune disorders, the researchers said.
A disease in which the body’s own immune system attacks nerve cells in the spinal cord and brain, MS is a major cause of neurological disease in younger adults, from 20 to 50 years of age, and disproportionally affects women. While treatable, there is no cure for MS, which can lead to problems with vision, muscle control, balance, basic body functions, among other symptoms, and could lead to disability.
Available treatments have adverse side effects as they focus on slowing the progression of the disease through suppression of the immune system.
Thanks to the collaboration between scientists at UTMB, Duke, University of California, Berkeley, and Case Western Reserve University, researchers found that when two particular DNA variants in the DDX39B and IL7R genes are present in a person’s genetic code, their interaction can lead to an over production of a protein, sIL7R. That protein’s interactions with the body’s immune system plays an important, but not completely understood, role in MS.
“Our study identifies an interaction with a known MS risk gene to unlock a new MS candidate gene, and in doing so, open up a novel mechanism that is associated with the risk of multiple sclerosis and other autoimmune diseases,” said Simon Gregory, director of Genomics and Epigenetics at the Duke Molecular Physiology Institute at Duke University Medical Center and co-lead author of the paper in Cell.
This new information has potentially important applications.
“We can use this information at hand to craft tests that could allow earlier and more accurate diagnoses of multiple sclerosis, and uncover new avenues to expand the therapeutic toolkit to fight MS, and perhaps other autoimmune disorders,” said Gaddiel Galarza-Muñoz, first author on the study and postdoctoral fellow at UTMB.
It can sometimes take years before an MS patient is properly diagnosed allowing the diseases to progress and resulting in further damage to the nervous system before treatment begins.
With more accurate measures of risk, health care providers would be able to screen individuals with family histories of MS or with other suspicious symptoms. It could lead those with certain genotypes to be more vigilant.

University of Texas Medical Branch
www.utmb.edu/newsroom/article11473.aspx

Researchers from Trinity College Dublin have shown for the first time that Motor Neurone Disease (MND) — also known as Amyotrophic Lateral Sclerosis (ALS) — and schizophrenia have a shared genetic origin, indicating that the causes of these diverse conditions are biologically linked.
By analysing the genetic profiles of almost 13,000 MND cases and over 30,000 schizophrenia cases, the researchers have confirmed that many of the genes that are associated with these two very different conditions are the same.
In fact, the research has shown an overlap of 14% in genetic susceptibility to the adult onset neuro-degeneration condition ALS/MND and the developmental neuropsychiatric disorder schizophrenia.
While overlaps between schizophrenia and other neuropsychiatric conditions including bipolar affective disorder and autism have been shown in the past, this is the first time that an overlap in genetic susceptibility between MND and psychiatric conditions has been shown.
Dr Russell McLaughlin, Ussher Assistant Professor in Genome Analysis at Trinity College Dublin, and lead author of the paper said: “This study demonstrates the power of genetics in understanding the causes of diseases."
"While neurological and psychiatric conditions may have very different characteristics and clinical presentations, our work has shown that the biological pathways that lead to these diverse conditions have much in common.”
Professor of Neurology in Trinity and Consultant Neurologist at the National Neuroscience Centre at Beaumont Hospital Dublin, Orla Hardiman, is the senior author and lead investigator on the project.
Professor Hardiman said: “Our work over the years has shown us that MND is a much more complex disease than we originally thought. Our recent observations of links with psychiatric conditions in some families have made us think differently about how we should study MND. When combined with our clinical work and our studies using MRI and EEG, it becomes clear that MND is not just a disorder of individual nerve cells, but a disorder of the way these nerve cells talk to one another as part of a larger network.”
She continued: “So instead of thinking of MND as a degeneration of one cell at a time, and looking for a ‘magic bullet’ treatment that works, we should think about MND in the same way that we think about schizophrenia, which is a problem of disruptions in connectivity between different regions of the brain, and we should look for drugs that help to stabilise the failing brain networks." 
“The other significant issue that this research brings up is that the divide between psychiatry and neurology is a false one. We need to recognise that brain disease has many different manifestations, and the best way to develop new treatments is to understand the biology of what is happening. This will have major implications for how we classify diseases going forward, and in turn how we train our future doctors in both psychiatry and neurology. That in itself will have knock-on consequences for how society understands, approaches and treats people with psychiatric and neurological conditions."
The new research was prompted by earlier epidemiological studies by researchers at Trinity, led by Professor Hardiman. These studies showed that people with MND were more likely than expected to have other family members with schizophrenia, and to have had another family member who had committed suicide.
This was first noted as family histories were ascertained from people with MND in the National ALS Clinic and was subsequently investigated as part of case control studies in Ireland in which over 192 families with MND and 200 controls participated. Details of over 12,000 relatives were analysed and the rates of various neurological and psychiatric conditions calculated in family member of those with MND and controls. This work was subsequently published in the prestigious American journal the Annals of Neurology in 2013.
This led the Trinity group to team up with European collaborators in MND including the University of Utrecht, Kings College London and members of the Project MinE and Psychiatric Genome Consortia to see if these epidemiological observations could be due to a genetic overlap between MND and schizophrenia.
The Trinity group, along with their partners in the University of Utrecht, will continue to study the links between MND and psychiatric conditions using modern genetics, epidemiology and neuroimaging, and in this way will develop new and more effective treatments that are based on stabilizing disrupted brain networks.

Trinity College Dublin
www.tcd.ie/news_events/articles/scientists-discover-shared-genetic-origin-for-mnd-and-schizophrenia/7681

National Human Genome Research Institute (NHGRI) researchers have identified new genes associated with the Erdheim-Chester disease (ECD) and some possible new therapies.  This ultra-rare disease is found in approximately 600 people in the world.
"The discovery of new genes associated with ECD provides hope for improving the diagnoses of a disease that affects so many parts of the body. We also hope it will help us identify new treatments," said Juvianee I. Estrada-Veras, M.D., clinical investigator and staff clinician in NHGRI’s Medical Biochemical Genetics Residency Program. "Our work on ECD builds on the institute’s goals to advance medical knowledge about rare diseases and to potentially provide insights into more common disorders."
ECD is caused by the accumulation of specialized white blood cells called histiocytes in different organs. The resulting inflammation damages organs and tissues throughout the body, causing them to become thickened, dense and scarred. Histiocytes normally function to destroy foreign substances and protect the body from infection. ECD has no standard therapy, although consensus guidelines for clinical management were published in 2014.
Between 2011 and 2015, researchers examined 60 adults with ECD at the NIH Clinical Center. Of 59 samples that were available for molecular testing, half had BRAF V600E gene mutations, which is sometimes seen in colon cancer, lung cancer, thyroid cancer, brain tumours and some blood cancers. Other patients had mutations in genes of the MAPK pathway, which controls cell growth and proliferation. These findings indicate that, despite the presence of inflammation and the absence of metastases (spread of cancer cells from the place where they first formed to another part of the body), ECD should be considered a type of cancer and treated by oncologists, researchers wrote.
Until now, the most common treatment for ECD has been interferon, a drug that interferes with the division of cancer cells and slows tumour growth. Some patients with severe forms of disease can succumb to the illness even with treatment. The mortality rate for ECD has been estimated at 60 percent at 3 years from the time of diagnosis.
Researchers suggested that therapies that stop the growth and proliferation of cells by blocking the MAPK pathway — vemurafenib, dabrafenib and trametinib — may provide new hope for treating and improving the survival of people with ECD. A therapeutic trial of dabrafenib and trametinib is now enrolling new ECD patients with BRAF V600E mutations.

National Human Genome Research Institute
www.genome.gov/27568398/2017-news-feature-genes-associated-with-erdheimchester-disease-also-linked-to-cancer/

Over a fourth of the eighty samples tested positive for new psychoactive substances.
In the last decade hundreds of new psychoactive substances (NPS) have emerged in the drug market, taking advantage of the delay occurring between their introduction into the market and their legal ban.  According to the Drug Enforcement Agency (DEA) NPS describes a recently emerged drug that may pose a public health threat.  The DEA issues a quarterly Emerging Threat Report, which catalogues the newest identified NPS.
NPS tend to mimic the psychotropic effects of traditional drugs of abuse, but their acute and chronic toxicity, and side-effects are largely unknown.  While seizure data from the DEA is often used to indicate what new drugs are being sold in the US, there is a lack of research examining and confirming who has been using such drugs.
Joseph J. Palamar, PhD, MPH, a New York University researcher, has been researching incidental and intentional use of NPS by young adults.  His current line of inquiry has focused on survey methods, qualitative interviews, and hair sampling to ascertain frequency and type of NPS use by nightclub-goers–a demographic which traditionally has a relaxed view towards recreational drug experimentation and use.
NPS are common adulterants in drugs such as ecstasy (MDMA), which has seen an increase in popularity since it became marketed as “Molly”.  Ironically, “Molly” connotes a product that is pure MDMA. In a related study, Palamar and his team found that four out of ten nightclub/festival attendees who used ecstasy or “Molly” tested positive for “bath salts” despite reporting no use.
In their current study, “Hair Testing for Drugs of Abuse and New Psychoactive Substances in a High-Risk Population,” Dr. Alberto Salomone, an affiliated researcher at the Centro Regionale Antidoping e di Tossicologia “A. Bertinaria”, Orbassano, Turin, Italy and Dr. Palamar, affiliated with NYU’s Center for Drug Use and HIV Research (CDUHR), collected hair samples from 80 young adults outside of New York City nightclubs and dance festivals, from July through September of 2015.  Hair samples from high-risk nightclub and dance music attendees were tested for 82 drugs and metabolites (including NPS) using ultra-high performance liquid chromatography–tandem mass spectrometry.
“Hair analysis represents a reliable and well-established means of clinical and forensic investigations to evaluate drug exposure, said Dr. Salomone.  “Hair is the most helpful specimen when either long-time retrospective information on drug consumption is of interest.” “Most NPS can no longer be detected in urine, blood, or saliva within hours or days after consumption, but hair is particularly beneficial because many drugs can be detected months after use.”
Of the eighty samples, twenty-six tested positive for at least one NPS—the most common being a “bath salt” (synthetic cathinone) called butylone (present in twenty-five samples). The “bath salts” methylone and even alpha-PVP (a.k.a.: “Flakka”) were also detected. The researchers find the presence of Flakka alarming as this drug has been associated with many episodes of erratic behaviour and even death in Florida. Other new drugs detected included new stimulants called 4-FA and 5/6-APB.
“We found that many people in the nightclub and festival scene have been using new drugs and our previous research has found that many of these people have been using unknowingly,” said Dr. Palamar, also an assistant professor of Population Health at NYU Langone Medical Center (NYULMC).
Hair analysis proved a powerful tool to Drs. Salomone and Palamar and their team, allowing them to gain objective biological drug-prevalence information, free from possible biases of unintentional or unknown intake and untruthful reporting of use.

NYU Langone Medical Center
www.nyu.edu/about/news-publications/news/2017/march/hair-testing-shows-high-prevalence-of-new-psychoactive-substance.html