TMEM63C

Alzheimer's disease is diagnosed with a range of cognitive and memory tests, but there's no definitive diagnostic test for the disease. But researchers have been able to use machine learning to evaluate MRI scans, diagnosing the disease in a single scan. For that and more research news, continue reading. Scientists Diagnose Alzheimer's with Single Scan Researchers at Imperial College London leveraged machine learning to examine structural features within the brain to diagnose Alzheimer's disease. Using this method, they also scanned parts of the brain not previously linked to Alzheimer's and was able to identify the disease at an early stage. Currently, diagnosis is via several cognitive tests, including memory tests, cognitive tests and brain scans. The scans look for evidence of protein deposits in the brain and shrinking of the hippocampus, the brain area associated with memory. The new scan uses MRI and an algorithm to classify cancer tumors modified for the brain. They split the brain into 115 regions and specified 660 features, such as size, shape and texture, to evaluate each region. They then programmed the algorithm to identify where changes accurately predict the existence of Alzheimer's. Their research was published in the journal Communications Medicine. "Currently, no other simple and widely available methods can predict Alzheimer's disease with this level of accuracy, so our research is an important step forward," Dr. Eric Aboagye, the lead researcher in the study, said. "Many patients who present with Alzheimer's at memory clinics do also have other neurological conditions, even within this group our system could pick out those patients who had Alzheimer's from those who did not." Leveraging data from the Alzheimer's Disease Neuroimaging Initiative, the researchers tested their approach on brain scans from more than 400 patients with early and late-stage Alzheimer's and individuals with other neurological disorders, including frontotemporal dementia and Parkinson's disease. They also evaluated data from more than 80 patients undergoing diagnostic testing at Imperial College Healthcare NHS Trust. In 98% of cases, their approach alone accurately predicted whether the patient had Alzheimer's or not. It could also distinguish between early and late-stage Alzheimer's with 79% accuracy. Women Underrepresented in Clinical Trials for 3 Key Disease Areas A study out of Brigham and Women's Hospital found that female participation in three specific disease areas lags behind their representation in the specific disease population. The key areas are adult cardiovascular, psychiatric, and cancer-related clinical trials. The study authors note that the disparity was particularly significant in clinical trials for drugs and devices for psychiatric disorders; in this area, women make up 60% of the patient population but only 42% of the trial participants. They analyzed 1,433 clinical trials with 302,664 participants and found that, on average, 41.2% of participants were female. In CV diseases, 49% of the patient population is female, but only 41.9% of trial participants were female. In cancer, 51% of cancer patients are female, but only 41% of clinical trial participants were female. Abnormal Lipid Processing May Drive Motor Neuron Diseases Researchers at the University of Exeter identified a new gene, TMEM63C, that appears linked to a degenerative disease affecting the nervous system's upper motor neuron cells. This supports their research into motor neuron degenerative diseases (MNDs), a large family of neurological disorders, suggesting they are the result of abnormal lipid processing in cells. Although MNDs are caused by changes in several different genes, the TMEM63C gene codes for a protein located in the region of the cell where the lipid processing pathways occur. They hypothesize that the appropriate maintenance of specific lipid processing pathways is vital to how brain cells function, and further, that abnormalities in the paths are common in motor neuron degenerative diseases. Females More Likely Than Males to Suffer Long COVID A new study from the Health of Women Team at the Johnson & Johnson Office of the Chief Medical Officer found that females were more likely to suffer from Long COVID and that females tended to present with different symptoms and/or disorders than males. In their data analysis of about 1.3 million patients, females presented with a range of symptoms, including ear, nose and throat issues, mood, neurological, skin, gastrointestinal and rheumatological disorders, and fatigue. Males, on the other hand, were more likely to experience endocrine disorders like diabetes and kidney disorders. Why this is the case isn't understood, but they suspect fundamental sex differences in the immune function may drive the differences in Long COVID. Females tend to have faster, more robust innate and adaptive immune responses that can protect them from initial infection and severity, but that may make them more vulnerable to prolonged autoimmune-related diseases. One of the problems with the study is that despite a large number of patients overall, only 35 articles of the 640,634 total articles in the literature offered sex-disaggregated data with enough details about symptoms to provide information about how the disease differed between males and females. New Combo Treatment for Pediatric T-Acute Leukemia Acute lymphoblastic leukemia (ALL) is the most common form of pediatric cancer, and the T-ALL type of leukemia has a poorer prognosis than B-lineage ALL. A study by Tampere University's Faculty of Medicine and Health Technology in Finland, the Massachusetts General Research Institute and the Harvard Stem Cell Institute identified a new drug combination that appears effective against T-ALL. Tampere had earlier found that Bristol Myers Squibb's Sprycel (dasatinib), a general tyrosine kinase inhibitor, was effective in about one-third of the tested patient samples, but its efficacy faded quickly. They found that treating the patients with dasatinib and temsirolimus (Pfizer's Torisel), which inhibits a parallel signaling pathway, was more effective in eradicating leukemia cells in zebrafish and human disease than a single drug. "This is a promising new treatment option for T-acute leukemia," Olli Lohi, M.D., Ph.D., research director at Tampere University and Tays Hospital's Cancer Centre, said. "The next step is to take the discovery into clinical practice for patients with relapsed or refractory disease via early phase clinical trials."

A new genetic discovery adds weight to a theory that motor neuron degenerative diseases are caused by abnormal lipid (fat) processing pathways inside brain cells. This theory will help pave the way to new diagnostic approaches and treatments for this group of conditions. The discovery will provide answers for certain families who have previously had no diagnosis. A new genetic discovery adds weight to a theory that motor neurone degenerative diseases are caused by abnormal lipid (fat) processing pathways inside brain cells. This theory will help pave the way to new diagnostic approaches and treatments for this group of conditions. The discovery will provide answers for certain families who have previously had no diagnosis. Motor neurone degenerative diseases (MNDs) are a large family of neurological disorders. Currently, there are no treatments available to prevent onset or progression of the condition. MNDs are caused by changes in one of numerous different genes. Despite the number of genes known to cause MNDs, many patients still remain without a much-needed genetic diagnosis. A University of Exeter team led by Professor Andrew Crosby and Dr Emma Baple has a long history of research in motor neurone degenerative diseases. The team developed a hypothesis to explain a common cause of MNDs stemming from their discovery of 15 genes responsible for MNDs. The genes they identified are all involved in processing lipids -- in particular cholesterol -- inside brain cells. in the new hypothesis published in the leading neurology journal Brain, describes the specific lipid pathways that the team believe are important in the development of MNDs. Now, the team has identified a further new gene -- named "TMEM63C" -- which causes a degenerative disease that affects the upper motor neurone cells in the nervous system. Also published in Brain, their latest discovery is important as the protein encoded by TMEM63C is located in the region of the cell where the lipid processing pathways they identified operate. This further bolsters the hypothesis that MNDs are caused by abnormal processing of lipids including cholesterol. Professor Andrew Crosby, at the University of Exeter, said: "We're extremely excited by this new gene finding, as it is consistent with our hypothesis that the correct maintenance of specific lipid processing pathways is crucial for the way brain cells function, and that abnormalities in these pathways are a common linking theme in motor neurone degenerative diseases. It also enables new diagnoses and answers to be readily provided for families affected by some forms of MND" MNDs affect the nerve cells that control voluntary muscle activity such as walking, speaking and swallowing. There are many different forms of MNDs which have different clinical features and severity. As the condition progresses, the motor neurone cells become damaged and may eventually die. This leads to the muscles, which rely on those nerve messages, gradually weakening and wasting away. If confirmed, the theory could lead to scientists to use patient samples to predict the course and severity of the condition in an individual, and to monitor the effect of potential new drugs developed to treat these disorders. In the latest research, the team used cutting-edge genetic sequencing techniques to investigate the genome of three families with individuals affected by hereditary spastic paraplegia -- a large group of MNDs in which the motor neurons in the upper part of the spinal cord miscommunicate with muscle fibres, leading to symptoms including muscle stiffness, weakness and wasting. These investigations showed that changes in the TMEM63C gene were the cause of the disease. In collaboration with the group led by Dr Julien Prudent at the Medical Research Council Mitochondrial Biology Unit at the University of Cambridge, the team also undertook studies to learn more about the functional relevance of the TMEM63C protein inside the cell. Using state-of-the-art microscopy methods, the Cambridge team's work showed that a subset of TMEM63C is localised at the interface between two critical cellular organelles, the endoplasmic reticulum and the mitochondria, a region of the cell required for lipid metabolism homeostasis and proposed by the Exeter team to be important for the development of MNDs. In addition to this specific localisation, Dr Luis-Carlos Tabara Rodriguez, a Postdoctoral Fellow in Dr. Prudent's lab, also uncovered that TMEM63C controls the morphology of both the endoplasmic reticulum and mitochondria, which may reflect its role in the regulation of the functions of these organelles, including lipid metabolism homeostasis. Dr Julien Prudent, of the MRC Mitochondrial Biology unit, said: "From a mitochondrial cell biologist point of view, identification of TMEM63C as a new motor neurone degenerative disease gene and its importance to different organelle functions reinforce the idea that the capacity of different cellular compartments to communicate together, by exchanging lipids for example, is critical to ensure cellular homeostasis required to prevent disease." Dr Emma Baple, of the University of Exeter, said: "Understanding precisely how lipid processing is altered in motor neurone degenerative diseases is essential to be able to develop more effective diagnostic tools and treatments for a large group of diseases that have a huge impact on people's lives. Finding this gene is another important step towards these important goals" The Halpin Trust, a charity who support projects which deliver a powerful and lasting impact in healthcare, nature conservation and the environment, part-funded this research. Claire Halpin, the charities' co-founder with her husband Les said "The Halpin Trust are extremely proud of the work ongoing in Exeter, and the important findings of this highly collaborative international study. We're delighted that the Trust has contributed to this work, which forms part of Les's legacy. He would also have been pleased, I know." The HSP Support Group is a UK charity providing help for people diagnosed with Hereditary Spastic Paraplegia (HSP). Adam Lawrence, the Group's Chair said "Finding a new type of HSP is extremely important as it helps reduce the uncertainty which people with the condition often have on their diagnosis journey. The work of the team in Exeter investigating HSP and its genetic causes over many years is world-leading and has increased the global understanding of HSP. Their work is important providing much needed answers for people with HSP, and developing treatments."