GAT1

COMBINEDBrain takes steps to break down language barriers perpetuating health inequity in research by translating patient registry informed consent and health surveys into three languagesNASHVILLE, Tenn., Sept. 29, 2022 (GLOBE NEWSWIRE) -- COMBINEDBrain (Consortium for Outcome Measures and Biomarkers for Neurodevelopmental Disorders), a non-profit organization of patient advocacy groups representing rare genetic neurodevelopmental disorders, is pleased to announce they have been awarded a Global Genes Health Equity RARE Patient Impact Grant which will be used to translate the ClinGen Health Surveys into French, German, and Italian, in addition to Spanish and English which are currently available. These additional languages will allow more rare disease patients from around the world to participate in research. This spring, as members of COMBINEDBrain met to plan the launch of natural history studies, it became apparent that language was a major barrier to recruiting patients from all parts of the world. Without exception, these groups found that offering English-only study documents delayed community engagement and enrollment. Many families of people with rare diseases express strong interest in sharing their experiences. Patients and caregivers understand the importance of natural history research in improving understanding of rare and ultra-rare diseases. Many organizations in COMBINEDBrain are working with Across Healthcare’s Matrix to collect patient-centered data. Matrix has platform menus and navigation tools available in Spanish, French, German, and Italian. However, the consent forms and surveys were not available in multiple languages. Many families for whom English is not their first language expressed difficulty understanding the informed consent and the health survey questions. “For individuals and families facing a rare disease, the journey is already incredibly difficult,” said Craig Martin, CEO of Global Genes. “For those in historically underserved or marginalized communities, the struggle is often even more challenging. Through our Impact grants, we are pleased to support leaders on a global scale with resources to more effectively collect, create and share information and to help lessen burdens and improve experiences and outcomes for underrepresented members of the rare disease community.” The Global Genes health equity grant will help to break down this language barrier and improve health equity in research and treatment of rare neurodevelopmental disorders. The ClinGen surveys are a National Institutes of Health (NIH) funded resource designed to collect consistent health histories for use in precision medicine and research. The grant will fund medical-grade translation of these respected surveys by LanguageLink into languages other than English. COMBINEDBrain plans to share the translations back to the ClinGen Project for dissemination around the world. Breaking down language barriers is necessary in order to include the experience of diverse populations in health research. Increasing diversity leads to improved research, diagnosis, standards of care, and a more comprehensive and inclusive understanding of disease and the patient journey. “COMBINEDBrain represents neurodevelopmental disorders, but the impact of these translations will go far beyond our scope, to help increase diversity in research on genetic disorders around the world. I am so proud of the leaders of our member groups, who had the vision to be inclusive and collaborative, and so grateful to Global Genes for incentivizing this work.” “Within rare disease populations, there is a dire need to be as inclusive as possible by breaking down any barriers. In the past, a huge barrier has been providing data collection platforms only in English. Our Matrix rare disease platform was architected to have multilingual support at its core,” states Jason Colquitt, CEO of Across Healthcare. "This grant is exciting and promising since it will allow us to unlock the ClinGen surveys for French, German, and Italian speaking patients and caregivers who would have previously never been able to participate without these translations. This is a huge win for everyone!” COMBINEDBrain non-profit 501c3 organization with a mission to speed the path to clinical treatments for people with severe rare genetic neurodevelopmental disorders: https://combinedbrain.org ASXL Rare Research Foundation CACNA1A Foundation Coalition to Cure CHD2CureSHANK DYRK1A Syndrome International Foundation FamiliesSCN2A Foundation Foundation for Hao-Fountain Syndrome FOXG1 Research Foundation Glut1 Deficiency FoundationGRIN2B FoundationiDefine Foundation (Kleefstra) KIF1A.ORGNR2F1 FoundationSATB2 Gene FoundationSETBP1 SocietySLC6A1 ConnectShwachman-Diamond Syndrome Alliance IncThe Yellow Brick Road Project (HNRNPH2) Kristin Hatcherkristinhatcher@combinedbrain.org

– Researchers will now be able to access rich clinical data on patients with rare neurological disease – SAN FRANCISCO, Sept. 12, 2022 /PRNewswire/ -- Invitae ( NYSE: NVTA), a leading medical genetics company, today announced a collaboration with Simons Searchlight, an international research program with a goal of accelerating research and improving lives for people with rare genetic neurodevelopmental disorders. This partnership will connect two sets of data – the longitudinal clinical data extracted from medical records through Invitae's Ciitizen, a patient-consented, digital natural history data platform and patient reported outcomes and biospecimens collected by Simons Searchlight. The partnership breaks down data silos and provides a rich and deep dataset that will help accelerate research for rare neurodevelopmental diseases. "We are excited about this collaboration that will allow researchers to get deep, rich longitudinal data on rare disease patients," said Farid Vij, president and general manager of data for Invitae. "This is intended to help improve treatment, with a goal of ultimately finding a cure for these rare diseases." Rare disease patients and caregivers are often asked to participate in many different stand- alone studies to help advance research. Through the combined clinical and patient-reported data in these two datasets, researchers get a deeper understanding of the etiology and progression of disease, sparing additional time, effort and data collection from the patient. "Joining forces with Invitae is incredibly powerful for patients with rare diseases," said Jennifer Tjernagel, M.S., senior project manager at Simons Searchlight, Simons Foundation. "Our partnership and the resulting datasets will help improve understanding, diagnosis and treatment of neurodevelopmental disorders, such as STXBP1, SYNGAP1 and others. Having the support of Invitae's Ciitizen platform will help pair patient-reported data with clinical information for in depth data analysis." Charlene Son Rigby, president and co-founder of STXBP1 Foundation shared, "We are thrilled to partner with Invitae and Simons Searchlight on this initiative. We believe in the power of data and how important sharing that data can be in the journey to finding a cure for STXBP1 Disorder. Having this kind of collaboration in our toolkit is opening up an entirely new approach for our foundation and our patient community. The combination of Invitae's existing clinical data which will be transitioned into a readily usable format, and Simons' deep information from patients and caregivers, will provide doctors and scientists with an innovative way to accelerate understanding of natural history, while allowing patients and their loved ones to focus on what's most important - their health." Mike Graglia, Managing Director and Co-Founder of the SynGAP Research Fund stated, "Invitae's Ciitizen is a powerful digital natural history study data platform in the rare disease space. The technology, execution and clinical expertise behind it are exceptional. Simons Searchlight is the most established clinician-led registry in autism and related disorders. The accomplishment of connecting these two platforms is a testament to their collective focus on helping patients. Every single patient who has access to Invitae's Ciitizen platform and Searchlight should consent to join their profiles now." This agreement expands upon a partnership that was originally launched as a pilot for STXBP1 patients and the STXBP1 Foundation. The relationship allowed consenting patients to link their de-identified Invitae Ciitizen data with the Simons Searchlight database to accelerate understanding of patients with STXBP1 disorder. By expanding focus to additional rare neurological disorders, such as SYNGAP1, SCN2A, SLC6A1 and more, researchers are one step closer to finding the needle in the haystack for patients with these conditions. To learn more about Invitae's Ciitizen data platform and request access to the consented dataset for research, email [email protected] About Invitae Invitae Corporation ( NYSE: NVTA) is a leading medical genetics company, whose mission is to bring comprehensive genetic information into mainstream medicine to improve healthcare for billions of people. Invitae's goal is to aggregate the world's genetic tests into a single service with higher quality, faster turnaround time and lower prices. For more information, visit the company's website at invitae.com. About Simons Searchlight Simons Searchlight collects medical, developmental, and behavioral data on people living with rare developmental disorders. Participants and their families share this valuable information and experiences so that scientists around the world may increase understanding of these medical conditions and ultimately improve lives. For more information, visit simonssearchlight.org Safe Harbor Statement This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the availability, features and potential impact of the company's products; the company's belief that it is the first and only laboratory to offer this comprehensive suite of tests for neurodevelopmental disorders in an easily accessible format; the company's belief that its NDD package is affordable and fast; and the company's belief that its NDD package will inform care decisions and treatment plans for patients. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially, and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: the company's history of losses; the company's ability to compete; the company's failure to manage growth effectively; the company's need to scale its infrastructure in advance of demand for its tests and to increase demand for its tests; the company's ability to use rapidly changing genetic data to interpret test results accurately and consistently; security breaches, loss of data and other disruptions; laws and regulations applicable to the company's business; and the other risks set forth in the company's filings with the Securities and Exchange Commission, including the risks set forth in the company's Annual Report on Form 10-K for the year ended December 31, 2021. These forward-looking statements speak only as of the date hereof, and Invitae Corporation disclaims any obligation to update these forward-looking statements. Contact: Renee Kelley [email protected] (628) 213-3283 SOURCE Invitae Corporation

Scientists elucidate, for the first time, the structure of the GABA transporter 1 (GAT-1) protein using cryogenic electron microscopy. The findings could lead to new, better treatments for neurological disorders such as anxiety, autism spectrum disorder, schizophrenia and Parkinson's disease. Scientists have, for the first time, revealed at the atomic level the structure of a protein that carries one of the body's most important neurotransmitters into neurons. In determining the structure of this transporter protein -- one of the smallest proteins ever resolved -- the researchers open new avenues to improve drugs for a wide range of debilitating conditions, including epilepsy, bipolar disorder, schizophrenia, Parkinson's and Huntington's diseases, anxiety and autism spectrum disorder. The study appears June 8 in the journal Nature. Neurons relay signals to one another by sending neurotransmitters across gaps between them, called synapses. The molecule GABA (short for gamma-amino butyric acid) is one of the most prevalent neurotransmitters in the brain. When one neuron emits GABA, sending it out across a synapse toward a nearby neuron, GABA inhibits the activity of the receiving neuron. But sometimes conditions can go awry, and not enough GABA reaches the receiving neuron, which may then become overactive, sending too many electrical impulses. This can cause a number of debilitating effects, including seizures. Fortunately, certain drugs can help by blocking a protein called GAT-1 (short for GABA transporter 1). GAT-1 is responsible for recycling released GABA back into the emitting neuron. Once such GAT-1 inhibitor, tiagabine (brand name Gabitril), reduces GABA recycling, leaving more GABA in the synapse to reduce the receiving neuron's activity. Although tiagabine can be effective, the exact way it interacts with GAT-1 to inhibit GABA recycling has been a mystery. And knowing how they interact could help researchers one day make more effective drugs. To solve the mystery and see exactly how tiagabine binds to GAT-1, researchers at the USC Dornsife College of Letters, Arts and Sciences used highly advanced cryogenic electron microscopy, commonly known as cryo-EM. The technique involves freezing molecules at extremely low temperatures, near to where atoms and molecules stop moving altogether, and then imaging them with an electron microscope. USC recently unveiled its new cryo-EM facility in the Core Center of Excellence in Nano Imaging at the USC Michelson Center for Convergent Bioscience. Cornelius Gati, lead author on the study, and a team of USC Dornsife scientists observed GAT-1 in complex with tiagabine and used cryo-EM to visualize how the two interact. "Previous understanding of the inhibitor (tiagabine) was purely based on biochemical studies, which do not provide any details at the atomic scale," said Gati, assistant professor of biological sciences and chemistry at USC Dornsife. "We can now pinpoint specific parts of the drug that interact with the protein." Gati said this new insight suggests a previously unknown mechanism of inhibiting GAT-1 that involves a change in the protein's overall shape when tiagabine binds to it. The highly detailed information revealed by the study could help researchers improve drugs or develop new therapies for treating diseases related to GABA-controlled neurons. "These findings have direct implications on pharmacology as a whole, not only with respect to treating epilepsy, but many other diseases," Gati said, adding that the results point to further avenues of research. "We have a feeling that this newly revealed mechanism is much more common than is currently thought, so we will investigate this first by using structurally similar inhibitors, and then expand our search to other molecules." Gati also noted that resolving the structure of the interacting molecules using cryo-EM proved extremely challenging -- GAT-1 is one of the smallest proteins resolved with the technique, making it difficult to visualize even with such advanced technology. Their success, he said, will motivate scientists at USC and other institutions to determine the structure of other challenging membrane proteins, leading to further understanding of drug-protein interaction and improved therapeutics.