Adenomatous polyposis coli (APC) is a gene whose mutations are associated with a rare, hereditary form of colorectal cancer known as familial adenomatous polyposis. Research led by scientists at the Institut Pasteur and Inserm have recently demonstrated that mutations to this gene do not only lead to the emergence of colon polyps; they also harm the immune system, leaving it unable to tackle inflammation of the colonic mucosa. This dual impact supports the development of cancer.
Familial adenomatous polyposis is an inherited condition characterized, from puberty, by the formation of a very large number of polyps, small growths on the inner surface of the colon and the rectum which can develop into tumours. If left untreated, these polyps may result in colorectal cancer before the age of 40.
Colon cancer is one of the most deadly forms of cancer, and familial adenomatous polyposis currently represents 1% of all cases of colorectal cancer. Those affected by this hereditary disease therefore need close medical supervision.
Research led by scientists from the Institut Pasteur and Inserm recently demonstrated that mutations in the adenomatous polyposis coli (APC) gene, known to be involved in familial adenomatous polyposis, do not only lead to the emergence of colon polyps; they also harm the immune system, leaving it unable to tackle inflammation of the colonic mucosa. This dual impact may favour the development of cancer.
As Andrés Alcover, Head of the Lymphocyte Cell Biology Unit at the Institut Pasteur and last author of the paper, explains, "the APC protein, associated with the microtubule cytoskeleton, has a major effect on the structure and differentiation of intestinal epithelial cells. By disrupting these functions in intestinal cells, APC mutations can lead to the development of tumours."
Scientists already knew that APC mutations could influence the immune system, but they had not yet identified the molecular mechanisms involved and the link with colorectal cancer development. The teams of scientists elucidated how the APC protein activates a particular type of immune cell known as T lymphocytes. "The protein activates T lymphocytes using a factor known as NFAT," continues Andrés Alcover. "Polyposis patients have a mutant version of the gene, which leads to a deficiency in APC protein and could reduce the presence of NFAT in cell nuclei" – thereby preventing lymphocyte activation.
One family of T lymphocytes, known as regulatory T cells, is particularly sensitive to APC mutations. The scientists observed a dysfunction in these regulatory T cells – which are present in large numbers in the intestine – in mice with these mutations that are predisposed to develop polyposis like the patients. This dysfunction leads to a deregulation of the immune system in the intestine and a failure to control local inflammation. "This is the first time that we have characterized at molecular level how mutations in the APC protein affect the immune system, creating favourable conditions for cancer development", emphasizes Andrés Alcover.
These findings suggest that mutations in the APC gene play a dual role in the development of colorectal cancer. Not only do they trigger the development of polyps; they also reduce the action of the immune system, preventing it from controlling gut inflammation. This vicious circle supports the development of cancer.
Institut Pasteur
www.pasteur.fr/en/colon-cancer-apc-protein-affects-immunity-preventing-pre-cancerous-inflammation
 

Boxers and mixed martial arts fighters may have markers of long-term brain injury in their blood, according to a study.
“This study is part of a larger study to detect not just individual concussions but permanent brain injury overall at its earliest stages and to determine which fighters are at greatest risk of long-term complications,” said study author Charles Bernick, MD, of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas and member of the American Academy of Neurology. “Our study looked at data over a five-year period and found elevated levels of two brain injury markers in the blood; now the question is whether they may signify permanent traumatic brain injury with long-term consequences.”
Researchers measured two biological markers of brain injury. One is a brain protein called neurofilament light chain, the other is called tau. Both are components of nerve fibres that can be detected in the blood when the fibres are injured.
For the study, researchers took blood samples from 291 active professional fighters with an average age of 30, 44 retired fighters with an average age of 45 and 103 non-fighters with an average age of 30. The blood samples were then tested for levels of both proteins.
Researchers found that active professional fighters had higher levels of both proteins compared to retired fighters or non-fighters. For example, they found that levels of neurofilament light chain were 40 percent higher in active boxers than in non-fighters. They also found that the more a fighter sparred in the two weeks before the blood samples were taken, the higher the levels of neurofilament light chain in their blood.
Neither age, ethnicity nor number of professional fights in active fighters were linked to levels of either protein.
Bernick said while neurofilament light chain protein was higher in active fighters at the start of the study, levels did not increase significantly during the study period. On the other hand, there was a group of fighters who showed increasing levels of tau over time.
When the researchers looked at brain size, they found that for fighters who had increasing levels of tau over time, there was a 7 percent decline in the volume of their thalamus, which is located in the centre of the brain and regulates sleep, consciousness, alertness, cognitive function and language while also sending sensory and movement signals to other portions of the brain.
Finally, the study found that fighters with higher levels of neurofilament light chain protein did not do as well on computerized tests that measure the brain’s processing speed as the retired fighters and non-fighters.
“Our study found that higher levels of both proteins may be associated with repetitive head trauma,” said Bernick. “However, neurofilament light may be more sensitive to acute traumatic brain injury whereas tau may be a better measurement of cumulative damage over time. More research needs to be done to see how these may be used to monitor traumatic brain injury and the neurological consequences over time.”
A limitation of the study was the difference in the average age of active and retired fighters.

The American Academy of Neurology
www.aan.com/PressRoom/Home/PressRelease/1568

Parkinson’s disease is an insidious disease: by the time it manifests as the typical motor dysfunctions such as tremors or muscle rigidity, portions of the brain have already been irreversibly destroyed. By this stage, the disease will have often begun already decades earlier. In search of an early portent of the disease, researchers led by Prof. Paul Wilmes, head of the Eco-Systems Biology Group at the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg, may now have found one in the gut: they have shown that the bacterial community in the gut of Parkinson’s patients differs from that of healthy people even at a very early stage of the disease.
Experts have long been discussing the notion that Parkinson’s disease originates far outside the brain. According to the "dual hit" hypothesis, a hitherto unknown pathogen intrudes into the body through two ports of entry: the nose or the gastrointestinal tract. Once there, it sets a pathological process in motion, above all the misfolding of the protein alpha-synuclein. This is a protein whose exact function remains unknown. Among other things, it is presumed to be involved in the excretion of messengers such as dopamine. The misfolding of this protein could propagate through the nerve pathways, where – decades later – it produces the typical clumping in the dopaminergic cells, known as Lewy bodies, that are characteristic of Parkinson’s. Ultimately, nerve cells start to die off and the typical symptoms of Parkinson’s disease appear.
The researchers led by Wilmes, together with physicians Prof. Brit Mollenhauer and Prof. Wolfgang Oertel and their teams in Göttingen, Kassel and Marburg, explored the question of whether the early events in the course of the disease also change the bacterial community, the microbiome, at the two possible ports of entry. They took samples from the nose and gut of 76 Parkinson’s patients and 78 healthy control people who are taking part in a long-term study. They also examined the microbiome of 21 subjects diagnosed with iRBD, Idiopathic Rapid-Eye-Movement Sleep Behaviour Disorder. People with this sleep disorder have a greatly elevated risk of developing Parkinson’s disease later in life.
It turned out that the bacterial community of the gut differed considerably between all three groups. "Parkinson’s patients could be differentiated from healthy controls by their respective gut bacteria," explains the first author Dr. Anna Heintz-Buschart from the Eco-Systems Biology Group. And the majority of the differential bacteria showed similar trends in the iRBD group. For example, certain germs were more prevalent in one group while the count was lower in others. In the samples from the subjects’ nasal cavities, however, the researchers found no such differences. The study also revealed that certain gut microbes are associated with non-motor Parkinson’s symptoms, for example depression.
"We hope that, by comparing the groups, we will learn to better understand the role of the microbiome in the process of the disease and to find out what changes occur and when," Paul Wilmes explains. "This might deliver new starting points for early treatment of the disease. It would also be essential knowledge for one day being able to use the absence or presence of certain bacteria as a biomarker for early detection of the disease."

EurekAlert
www.eurekalert.org/pub_releases/2017-08/uol-abc082917.php

In an effort to provide customers with expanded, more comprehensive solutions for molecular testing, Siemens Healthineers has announced a new strategic relationship with Fast-track Diagnostics (FTD) that includes the addition of FTD’s broad range of CE-marked kits and multisyndromic panels to the menu of the Siemens Healthineers VERSANT kPCR Molecular System. The addition of FTD’s broad menu of kits and panels – which cover conditions from respiratory to gastroenteritis to central nervous system (CNS) and childhood infections – increases the breadth of Siemens Healthineers’ complete molecular testing solution, ensuring leading-edge performance from extraction through detection and increasing workflow efficiency for molecular labs of all sizes.
 “Over the past 24 months, Siemens Healthineers has made significant advancements in the delivery of molecular diagnostic applications and services,” says Fernando Beils, Head of Molecular Diagnostics, Siemens Healthineers. “We continue to strengthen and broaden our Molecular System by offering a comprehensive, scalable solution for accurate diagnosis and monitoring to our customers worldwide through our alliance with Fast-track Diagnostics.”
The VERSANT kPCR Molecular System, an established market player in molecular testing for HIV and Hepatitis, will now feature over 75 assays, consolidating testing for the infectious disease spectrum in a single molecular ecosystem.
“The VERSANT kPCR Molecular System is perfectly suited to our wide range of assays, which means laboratories can now diagnose nearly any infectious disease in one workflow,” says Bill Carman, CEO of Fast-track Diagnostics.
In offering customers the option of a single, consolidated system with a broad menu and virtually open platform, Siemens Healthineers enables healthcare providers to meet their current challenges, especially as an increasing push towards a value-based healthcare philosophy relies heavily on increased productivity and streamlined workflows. With this in mind, Siemens Healthineers has made its growth and enhancement within the molecular diagnostics space a key priority for its business strategy moving forward. www.siemens.com/healthineerswww.fast-trackdiagnostics.com

AP-HP teams in collaboration with researchers from the ICM (Inserm / CNRS / UPMC), and the start-up Metafora Biosystems, from the CNRS, have just developed a blood diagnostic test for a neurological disease rare but treatable, De Vivo’s disease.
It has been tested on 30 patients with this disease that induces neurological deficits such as epilepsy or walking disorders for example.
The new test will enable children and affected adults to be identified quickly (within 48 hours) and easily compared to current diagnostic tests that rely on invasive gestures, Lumbar puncture or complex DNA analysis.
De Vivo’s disease or syndrome of cerebral glucose transporter 1 (GLUT-1) deficiency is most often characterized by developmental delay, epilepsy and / or motor disorders in children. Frustrated forms have been described in children (access to abnormal movements) but also adults. Based on an estimated prevalence of 1/83 000 in the Danish population, the number of patients in France is estimated to be 800 , of which slightly more than 100 would be diagnosed. As soon as they are diagnosed, patients can benefit from metabolic treatments that decrease the symptoms.
In this study, blood samples from 30 patients with the disease with different profiles, according to age and symptoms, were analysed. Compared with 346 samples of control individuals, the results showed that the test was significantly conclusive with 78% of the diagnosis, including patients for whom the genetic analyses had not been able to establish the diagnosis.
Based on these results, researchers recommend the use of this test in clinical routine in all neurology and neurology departments. They suggest that the simplicity of this new test should increase the number of patients identified in France.
Thanks to this innovative new blood test, the disease can be sought in any patient with intellectual disability and / or epilepsy and / or a walking disorder. The treatments that can be implemented considerably improve the symptoms, such as the disappearance of epileptic seizures, and are all the more effective since they are started early, hence the importance of an early diagnosis .

The Bichat – Claude – Bernard Hospital
www.aphp.fr/contenu/un-test-sanguin-developpe-pour-detecter-une-maladie-rare-neurologique