In late July, Svar Life Science signed a strategic agreement to transfer the portfolio of radioimmunoassays (RIA) and the Chromogranin A Neolisa™ (ELISA) product to DIAsource ImmunoAssays, a BioVendor group company.
Svar Life Science AB (formerly Euro Diagnostica AB), a Swedish life science company that has been working across the clinical diagnostic value chain for over 30 years, and DIAsource ImmunoAssays, a leading diagnostics company delivering manual RIA and ELISA kits and open automation solutions to international markets, today announced a strategic agreement, under which Svar Life Science will transfer its portfolio of RIA products and the Neolisa™ CgA ELISA product to DIAsource, securing the continued production and sales of these products.
Svar Life Science will continue to invent, develop and apply the best analytical technologies, with a focus on helping deliver the answers needed in drug discovery and clinical diagnostics, and the impact this has on human lives.
This transaction strengthens DIAsource and BioVendor’s position as one of the top RIA and larger ELISA manufacturers, committed to servicing customers worldwide that use manual assays and open automation to complement their portfolio on closed automated systems.
The portfolio to be transferred includes the complete line of radioimmunoassays for the quantification of a number of peptide hormones involved in critical physiological processes. These endocrinological parameters are mainly used as tumour markers and for diabetology and salt balance analysis. The portfolio transfer also includes the ELISA Chromogranin A Neolisa™ product which complements the RIA Chromogranin A product.
In order to support a smooth transition with minimal disruption for customers, the companies have agreed to a transition period. Starting 1st of September 2018 DIAsource ImmunoAssays assumes sales of the RIA product portfolio. During the remainder of 2018 the RIA production will be transferred. Sales of the Neolisa™ CgA ELISA product will be assumed by DIAsource as of January 2019, with production transfer to follow during 2019.
Ron Long, CEO, Svar Life Science, said: “The agreement with DIAsource ImmunoAssays forms part of our strategy of focusing our product portfolio and core technologies to help deliver the answers needed in drug discovery and clinical diagnostics today. It also enables us to strengthen our support for life science customers providing high quality solutions, the best analytical technologies for drug development and clinical research.
DIAsource ImmunoAssays are committed to being a complete diagnostic provider and we’re confident that this agreement enables them to increase their support for customers in the field of radioimmunoassays.”  
Jef Vangenechten, CEO of DIAsource ImmunoAssays, said: “This acquisition is another step in our strategy to position DIAsource as a consolidator of manual specialty assays, after previous acquisitions of the Intertech RIA product line in 2012, Viro-Immun ELISA and IFA product lines in 2017, and more recently the RIA product line from ZenTech.”www.diasource-diagnostics.com

In the brain, as in business, connections are everything. To maintain cellular associates, the outer surface of a neuron, its membrane, must express particular proteins—proverbial hands that reach out and greet nearby cells. And, like a creepily long handshake, surface molecules can overstay their welcome: A protein that lingers too long on the membrane may compromise the connections, or synapses, between cells.
In a new study, Rockefeller scientist Mary E. Hatten and research associate Hourinaz Behesti demonstrate that the protein ASTN2 helps move proteins away from the membrane in a timely fashion. The researchers also propose a mechanism by which ASTN2 defects lead to neurodevelopmental disorders such as autism and intellectual disabilities.
Neurons send messages to one another in the form of chemicals, or neurotransmitters, which activate receptor proteins on the surface of neighboring cells. Chemical communication is highly dynamic, which means that receptors must be dynamic too: they perpetually rotate on and off the membrane, ensuring rapid response to incoming signals. This process requires assistance from additional proteins, so-called traffickers that nudge receptors to move along.
Hatten, the Frederick P. Rose Professor, has demonstrated that the protein ASTN2 acts as such a trafficker during cell migration in early development. When Behesti joined Hatten’s lab, she proposed that the protein might also play a role later in life, an idea supported by the fact that ASTN2 had been shown to be present in the adult brain. Specifically, the protein appears to be disproportionally expressed in the cerebellum—a brain region that some researchers suspect may govern complex aspects of cognition, in addition to its more-established role in regulating movement.
Hatten and Behesti wanted to better understand the function of ASTN2 in the adult cerebellum. An initial clue came by way of collaborators at Johns Hopkins University, who identified a family that had multiple members with ASTN2 mutations and neurodevelopmental disorders, including autism and language delays.
Concurrently, an independent study of a large population showed that ASTN2 mutations are associated with a wide variety of brain disorders. Hatten and Behesti therefore set out to determine how defects in this protein might disrupt cerebellar circuitry, and brain activity at large.
The researchers used a special microscopy technique to determine where ASTN2 is expressed in the mouse cerebellum. They found that it appears primarily in components of neurons responsible for moving proteins around, and they identified a collection of molecules that attach to ASTN2. These “binding partners” included proteins involved in synapse formation and protein trafficking.
When the researchers increased the expression of ASTN2 in mouse neurons, levels of its binding partners decreased, suggesting that ASTN2 attaches to these proteins and then ushers them away from the membrane for degradation within the cell. Working with researchers at Duke University, the scientists also observed that cells with heightened ASTN2 formed stronger synapses; and they suspect that decreased ASTN2 yields the opposite effect.
“Our data suggest that people who have mutations in ASTN2 make less of the protein, which leads to slower or weaker synapses,” says Behesti.
The researchers propose that without sufficient ASTN2, proteins accumulate on the cell surface, which hinders neuronal connections and communication.
“Synapses aren’t static. They need to respond in real time to dynamic stimuli; and one of the ways they do this is by changing their surface protein expression,” says Behesti.
This research supports a broader view that the disruption of surface protein composition may underlie a number of neurodevelopmental disorders. It also points to the cerebellum as a potentially fruitful research subject for understanding these conditions.
“People are just beginning to realize that the cerebellum isn’t just there to control movement and motor learning,” says Hatten. “It has much more complex roles in cognition and language.

Rockefeller University
www.rockefeller.edu/news/23712-study-protein-trafficker-provides-insight-autism-brain-disorders/

Opitz C syndrome (OCS), an ultra-rare disease that causes serious physical and intellectual disabilities, has an heterogeneous genetic base that makes its medical diagnostic and therapeutic intervention difficult, according to a new study by professors Daniel Grinberg, Susanna Balcells and Roser Urreizti, from the Group on Human Molecular Genetics of the of the Faculty of Biology of the University of Barcelona and the Rare Diseases Networking Biomedical Research Centre (CIBERER).
The new study concludes this severe and extremely rare disease could be considered a “private syndrome” for each patient.
Described in 1969 by geneticist John M. Opitz, this ultra-rare pathology –with only a few diagnosed cases worldwide- shows a great clinical variability in different levels of severity (trigonocephaly, intellectual disability, psychomotor retardation, among others). Therefore, clinical symptomatology of Opitz C syndrome can overlap other similar minority pathologies (Kleefstra, Kabuki, Bohring-Opitz syndromes, etc.).
However, despite sharing several clinical manifestations, “this disease does not show a genetic base shared by the affected people, and its hereditary transmission model is still unknown”, note the authors, also members of the Institute of Biomedicine of the University of Barcelona (IBUB) and the Research Institute Sant Joan de Déu (IRSJD).
Since 2007, several genes have been related to this pathology, which is hard to diagnose due its wide clinical pattern (for instance, ASXL1, CD96, ASXL3 and MAGEL2). In this context, research lines of the Group on Human Molecular Genetics (UB-CIBERER-HSJD) –in which Raquel Rabionet and Laura Castilla take part too- are broadening the knowledge of the genetic basis of this pathology which so far does not have any chance of receiving treatment, prenatal diagnosis nor genetic counselling.
“In these ultra-rare diseases, the application of new massive sequencing technologies is a determining factor regarding the molecular diagnosis for patients and therefore, to progress in the exploration of therapeutic applications”, comment the authors. 
In some cases, affected patients can receive an early diagnose –incomplete and too general- that makes any therapeutic intervention difficult. This is the case of a recent research study in which the Group on Human Molecular Genetics participated, and found two mutations in the PIGT gen in a patient who had initially been diagnosed Opitz C syndrome.
This study could profile a precise molecular diagnose of the causes of the real pathology –with a few cases gathered in the scientific bibliography- affecting the patient, considered as Opitz C at the beginning.
The international scientific collaboration has been determining in the genetic diagnosis of other cases with severe affectations in the neuro-development that had been considered to be Opitz C syndrome. In particular, the UB team has participated in the identification of new genetic mutations associated with DPH1 syndrome –a minority disease with a low prevalence among population- in patients of two different families from Malta and Yemen.
University of Barcelona https://tinyurl.com/yxdrze2f

An international team of researchers from the Hopp Children’s Cancer Centre at the NCT Heidelberg (KiTZ), the European Molecular Biology Laboratory (EMBL) and the German Cancer Consortium (DKTK) together with colleagues at the St. Jude Children’s Research Hospital in Memphis and the Hospital for Sick Children in Toronto has summarized hereditary gene defects which can trigger the development of certain malignant brain tumours (medulloblastoma). From their findings, the team has derived recommendations for routine genetic screening in medulloblastoma patients. Medulloblastoma is a rare malignant tumour of the cerebellum and occurs predominantly in children. Scientists believe that in many cases hereditary gene defects trigger the development of this malignant disease. However, there are no standards for routine genetic screening of patients, nor are there guidelines and a corresponding nationwide infrastructure for genetic counselling of affected families.
Scientists have now been able to characterize medulloblastoma more accurately and to derive recommendations for genetic testing based on analysis of 1022 patients with medulloblastoma. “We analysed genes that have been previously implicated in predisposition to any type of pediatric and adult cancer”, says Sebastian Waszak from the EMBL Heidelberg who is one of the study’s lead authors. It turned out that six genes were also frequently affected by genetic alterations in patients with medulloblastoma.
Considering the six significantly enriched genes, about five percent of patients had an increased risk of cancer. Taking into account all cancer risk genes, about eleven percent of the patients had an increased cancer risk. Looking at a particular tumour subgroup, the so called “SHH-activated medulloblastoma”, even 20 percent were identified to harbour a genetic predisposition to cancer.
These predisposing mutations occur in every single cell of the patient and can be also passed on to offspring. “Mutations of this kind often indicate a familial predisposition to cancer and therefore place special demands on the treatment of patients and the counselling of families”, said Paul Northcott from the St. Jude Children’s Research Hospital in Memphis, who shares the lead authorship. The results are particularly important because both materials from previous studies and patient data from four current or recently completed clinical trials were included in the analysis.
Based on these findings and other tumour features, the scientists developed criteria for routine genetic screening. “Hereditary disease factors usually have a significant impact on the whole family of the patient, We want to make genetic analysis available as a standard of care for patients with specific medulloblastoma”, says Stefan Pfister, KiTZ director, scientist at the German Cancer Research Centre, and senior physician at the Heidelberg University Hospital. To make this possible, Stefan Pfister and Christian Kratz from the Hannover Medical School have created a registry for patients with a hereditary cancer predisposition and a website that contains information for patients, families, and physicians (www.krebs-praedisposition.de).

The German Cancer Research Center (DKFZ)https://tinyurl.com/ya5akv4j