Liver Disease for Precision Medicine

Clusters of metabolic dysfunction-associated steatotic liver disease for precision medicine

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a heterogeneous disease regarding its pathophysiology and clinical outcomes. Two novel studies suggest that different clusters of people with MASLD exist, explaining part of this heterogeneity. These findings and future research applying data dimensionality reduction approaches might be beneficial for implementing precision medicine in MASLD.

The basic, translational and clinical content in Nature Reviews Gastroenterology & Hepatology is written by internationally renowned basic and clinical academics and researchers and targeted towards readers in the biological and medical sciences, from postgraduate level upwards. While intended to be read by practising doctors, researchers and academics within a specialty, we aim to make all our articles accessible to readers working in any biological or medical discipline.

In-depth Reviews present authoritative, up-to-date information on a topic, placing it in the context of a field's history and development. Consensus Statements provide evidence-based or eminence-based recommendations and present a balanced review put together by a task force of experts. Topical discussion and opinions are proffered in Perspectives, Comment and News & Views articles, and in the Research Highlights section we filter primary research from a range of specialty and general medical and scientific journals.

gene mutation, genomic sequencing, rare disorders, single nucleotide polymorphism, epigenetic alterations, copy number variations, chromosomal abnormalities, mitochondrial disorders, autosomal inheritance, recessive traits, precision medicine, CRISPR technology, genetic counseling, exome analysis, hereditary syndromes, phenotypic variability, non-coding DNA mutations, gene therapy breakthroughs

#Genetics #RareDiseases #GeneMutation #GenomicSequencing #PrecisionMedicine #CRISPR #GeneTherapy #GeneticCounseling #HereditarySyndromes #ChromosomalAbnormalities #Epigenetics #ExomeAnalysis #PhenotypicVariability #MolecularDiagnostics #RareSyndromes #InheritedDisorders #MitochondrialDiseases #CNVs #Transcriptomics #GeneticHealth

International Conference on Genetics and Genomics of Diseases

Visit: genetics-conferences.healthcarek.com

Award Nomination: genetics-conferences.healthcarek.com/award-nomination/?ecategory=Awards&rcategory=Awardee

Award registration: genetics-conferences.healthcarek.com/award-registration/

For Enquiries: contact@healthcarek.com

Get Connected Here
---------------------------------
---------------------------------
in.pinterest.com/Dorita0211
twitter.com/Dorita_02_11_
facebook.com/profile.php?id=61555903296992
instagram.com/p/C4ukfcOsK36
genetics-awards.blogspot.com/
youtube.com/@GeneticsHealthcare

Rare disease gene

Rare disease gene association discovery in the 100,000 Genomes Project

Up to 80% of rare disease patients remain undiagnosed after genomic sequencing1, with many probably involving pathogenic variants in yet to be discovered disease–gene associations. To search for such associations, we developed a rare variant gene burden analytical framework for Mendelian diseases, and applied it to protein-coding variants from whole-genome sequencing of 34,851 cases and their family members recruited to the 100,000 Genomes Project2. A total of 141 new associations were identified, including five for which independent disease–gene evidence was recently published. Following in silico triaging and clinical expert review, 69 associations were prioritized, of which 30 could be linked to existing experimental evidence.

The five associations with strongest overall genetic and experimental evidence were monogenic diabetes with the known β cell regulator3,4 UNC13A, schizophrenia with GPR17, epilepsy with RBFOX3, Charcot–Marie–Tooth disease with ARPC3 and anterior segment ocular abnormalities with POMK. Further confirmation of these and other associations could lead to numerous diagnoses, highlighting the clinical impact of large-scale statistical approaches to rare disease–gene association discovery.

Rare diseases collectively affect 3.5% to 5.9% of people worldwide5. Despite advances in genomic sequencing, molecular diagnosis continues to elude 50% to 80% of patients presenting to genetic clinics1. Furthermore, fewer than half of the 10,000 rare Mendelian diseases in the Online Mendelian Inheritance in Man (OMIM) database6 have an established genetic basis. Diagnostic failure may arise because of a lack of routine screening for non-coding7 or structural variants1. However, it is likely that a substantial proportion of the pathogenic variants responsible for patients undiagnosed with rare disease (cases) reside in those yet to be discovered genes associated with (possibly very rare) disorders.

The scale of rare disease sequencing studies, such as the Undiagnosed Disease Network8, Centers for Mendelian Genomics9, Deciphering Developmental Disorders10 and the 100,000 Genomes Project (100KGP)2, offers expanded opportunities to provide insight into pathogenic mechanisms of inherited disease, including the possibility of establishing disease–gene associations through case–control analyses, akin to methods used previously to identify common genetic variants influencing the risk of complex disorders. Such an approach provides much-needed power to identify genes harbouring rare pathogenic variants.

genetics awards, genomics, DNA research, hereditary science, gene editing, CRISPR recognition, genetic breakthroughs, medical genetics, population genetics, biotechnology awards, Nobel Prize in Genetics, genomic medicine, genetic innovation, molecular biology, personalized medicine, genetics research grants, bioinformatics, evolutionary genetics, genetic engineering, scientific excellence

#GeneticsAwards #Genomics #DNAResearch #HereditaryScience #GeneEditing #CRISPRRecognition #GeneticBreakthroughs #MedicalGenetics #PopulationGenetics #BiotechAwards #NobelPrizeGenetics #GenomicMedicine #GeneticInnovation #MolecularBiology #PersonalizedMedicine #GeneticsResearch #Bioinformatics #EvolutionaryGenetics #GeneticEngineering #ScientificExcellence

International Conference on Genetics and Genomics of Diseases

Visit: genetics-conferences.healthcarek.com

Award Nomination: genetics-conferences.healthcarek.com/award-nomination/?ecategory=Awards&rcategory=Awardee

Award registration: genetics-conferences.healthcarek.com/award-registration/

For Enquiries: contact@healthcarek.com

Get Connected Here
---------------------------------
---------------------------------
in.pinterest.com/Dorita0211
twitter.com/Dorita_02_11_
facebook.com/profile.php?id=61555903296992
instagram.com/p/C4ukfcOsK36
genetics-awards.blogspot.com/
youtube.com/@GeneticsHealthcare

Gene Therapy

Making Gene Therapy Faster And Better With Fuse Vectors

Moorfields Eye Hospital in London made international headlines last week. Doctors announced they had saved the sight of four young children suffering from a rare genetic condition that rapidly causes blindness. The toddlers were treated using gene therapy, through which patients are given a harmless virus containing healthy versions of a defective gene in order to remedy the problem.

“Gene therapy sounds like science fiction, but it is beginning to have a huge impact,” says Benjamin Blaha, co-founder of the gene therapy-focused Danish biotechnology start-up Fuse Vectors, which is today announcing a $5.2 million pre-seed fundraising round. “We desperately need to develop more of these treatments as quickly as possible, because they can save lives and transform patient outcomes.”

Fuse hopes to play a significant role in doing exactly that. Blaha and co-founders Jordan Turnbull and Henrik Stage believe that the bottleneck for gene therapy developers today lies in the manufacturing process, rather than in the science itself. “If we want to develop new treatments faster, more safely and more cheaply, we need to solve the manufacturing problem,” Blaha adds. “Traditional methods of manufacturing gene therapies are akin to asking a blacksmith to build a jet plane.”

Fuse is focused on the mechanics of getting treatments into the human body – the “vector” for transmission. Currently, gene therapies make use of human cells – a technique developed for other types of drug delivery – but working with live cells in this way is inefficient and difficult to control. Fuse’s innovation is a technique that enables cell-free production of the viral vectors required; using protein and DNA as building blocks, it constructs tailor-made vectors for delivering the treatment.

“This allows for greater precision, more efficiency and increased scalability,” explains Turnbull. “You get higher drug quality, improving safety and efficacy by eliminating unwanted by-products, increased development speed from research to clinical application, and reduced production costs that make advanced therapies more affordable.”

The potential gains are significant. Fuse believes that its finished product is so tightly controlled that patients will need only a fifth of the dose currently required from gene therapies, which should be far safer. It says it can develop a new viral vector for testing in just four hours – compared to the four weeks it takes to develop a cell in the traditional way. And it thinks costs could be dramatically lower.

All of which is hugely exciting for healthcare professionals and the patients they want to treat. “There are thousands of addressable diseases that we need these therapies for,” adds Blaha. “The opportunity is to transform people’s lives.”

That said, the company is at a relatively early stage – particularly in terms of commercialisation. Fuse is pre-revenue, though it has signed up around a dozen partners, ranging from pharmaceutical companies to academic institutions, which will trial its technology in the coming months. The two founders hope to convert some of those partners into paying customers before the end of the year.

The company is pursuing two business models, with plans both to develop its own gene therapies and to give access to its manufacturing process to other developers. “The key is just to develop these treatments as quickly as possible,” says Turnbull.

New funding for the business should help in this endeavour. Today’s $5.2 million round is led by HCVC, an early-stage venture capital firm with investments in both Europe and North America. “With its unique cell-free viral vector solution, expert founding team and strong business model, Fuse Vectors has the potential to overcome significant challenges in the field,” says HCVC managing partner Alexis Houssou. “We believe in their ability to bring transformative treatments to patients.”

The funding round has also won support from BioInnovation Institute, an international non-profit foundation supported by the Novo Nordisk Foundation, and Denmark’s Export & Investment Fund. At the former, chief business officer Trine Bartholdy, says: “Fuse’s approach has the potential to make gene therapy much more interesting for the industry to develop as well as to increase its accessibility to patients.”

gene therapy, genetic engineering, genome editing, CRISPR, gene modification, genetic disorders, DNA repair, viral vectors, non-viral delivery, somatic gene therapy, germline editing, gene expression, targeted therapy, biotechnology, precision medicine, RNA therapeutics, cell therapy, molecular medicine, hereditary diseases, biomedical research

#GeneTherapy #GeneticEngineering #GenomeEditing #CRISPR #GeneModification #GeneticDisorders #DNARepair #ViralVectors #NonViralDelivery #SomaticGeneTherapy #GermlineEditing #GeneExpression #TargetedTherapy #Biotechnology #PrecisionMedicine #RNATherapeutics #CellTherapy #MolecularMedicine #HereditaryDiseases #BiomedicalResearch

International Conference on Genetics and Genomics of Diseases

Visit: genetics-conferences.healthcarek.com

Award Nomination: genetics-conferences.healthcarek.com/award-nomination/?ecategory=Awards&rcategory=Awardee

Award registration: genetics-conferences.healthcarek.com/award-registration/

For Enquiries: contact@healthcarek.com

Get Connected Here
---------------------------------
---------------------------------
in.pinterest.com/Dorita0211
twitter.com/Dorita_02_11_
facebook.com/profile.php?id=61555903296992
instagram.com/p/C4ukfcOsK36
genetics-awards.blogspot.com/
youtube.com/@GeneticsHealthcare

Top in cardiology

Top in cardiology: Atherosclerosis common in lung cancer; treating amyloidosis

Patients beginning lung cancer treatment demonstrated a high prevalence of atherosclerosis, which suggests that they may benefit from calcium scoring, new data showed.

According to a presentation given at the American College of Cardiology’s Advancing theCardiovascular Care of the Oncology Patient course, more than three-quarters of patients entering lung cancer treatment who underwent chest CT imaging showed evidence of atherosclerosis.

White patients who smoked appeared most likely to have atherosclerosis on CT out of all the subgroups examined, researchers found.

“What this study confirms is that tobacco use is a shared risk factor for both diseases and at the time of lung cancer diagnosis these patients should be considered for additional evaluation by a cardiologist or cardio-oncologist, as it is likely they already have CV disease,” Christopher Malozzi, DO, director of cardio-oncology services at the University of South Alabama Frederick P. Whiddon College of Medicine, told Healio.

It was the top story in cardiology last week. In another top story, Joban Vaishnav, MD, director of the Johns Hopkins Comprehensive Amyloidosis Center, discussed the evolving treatment landscape of amyloidosis.

Read these and more top stories in cardiology below:

High prevalence of atherosclerosis detected in patients entering lung cancer therapy

cardiology, heart disease, cardiovascular health, arrhythmia, heart attack, stroke, hypertension, atherosclerosis, heart failure, echocardiography, angioplasty, stent placement, cardiac arrest, electrophysiology, myocarditis, cardiomyopathy, cholesterol, blood pressure, coronary artery disease, cardiovascular research,

#Cardiology #HeartHealth #CardiovascularDisease #HeartAttack #Stroke #Hypertension #Atherosclerosis #HeartFailure #Echocardiography #Angioplasty #StentPlacement #CardiacArrest #Electrophysiology #Myocarditis #Cardiomyopathy #Cholesterol #BloodPressure #CoronaryArteryDisease #HeartCare #CardiovascularResearch

International Conference on Genetics and Genomics of Diseases

Visit: genetics-conferences.healthcarek.com

Award Nomination: genetics-conferences.healthcarek.com/award-nomination/?ecategory=Awards&rcategory=Awardee

Award registration: genetics-conferences.healthcarek.com/award-registration/

For Enquiries: contact@healthcarek.com

Get Connected Here
---------------------------------
---------------------------------
in.pinterest.com/Dorita0211
twitter.com/Dorita_02_11_
facebook.com/profile.php?id=61555903296992
instagram.com/p/C4ukfcOsK36
genetics-awards.blogspot.com/
youtube.com/@GeneticsHealthcare

🧬International Conference on Genetics and Genomics of Diseases🧬

International Conference on Genetics and Genomics of Diseases

Rare genetic disorder

Rare genetic disorder treated in womb for the first time

A two-and-a-half-year-old girl shows no signs of a rare genetic disorder, after becoming the first person to be treated for the motor-neuron condition while in the womb. The child’s mother took the gene-targeting drug during late pregnancy, and the child continues to take it.

The “baby has been effectively treated, with no manifestations of the condition,” says Michelle Farrar, a paediatric neurologist at UNSW Sydney in Australia. The results were published in the New England Journal of Medicine yesterday.

The child was conceived with a genetic condition known as spinal muscular atrophy, which affects motor neurons that control movement, and leads to progressive muscle weakening. About one in every 10,000 births have some form of the condition — making it a leading genetic cause of death in infants and children.

In its most severe form, as in the case of this child, individuals lack both copies of the SMN1 gene, and have only one or two copies of a neighbouring gene, SMN2, that partially compensates for that deficiency. As a result, the body does not produce enough of the protein required for maintaining motor neurons in the spinal cord and brainstem. This protein is most important in the second and third trimesters, and the first few months of life. Babies with severe disease don’t usually live past their third birthday.

In the past decade, the US Food and Drug Administration (FDA) has approved three drugs to treat newborns for spinal muscular atrophy. The oral drug used in this study, called Risdiplam, manufactured by biotech firm Roche, based in Basel, Switzerland, is a small molecule that works by modifying expression of the SMN2 gene so that it produces more SMN protein.

Up until now, treatments for spinal muscular atrophy were given after birth. But up to half of newborns lacking both copies of the SMN1 gene and with only two copies of the SMN2 gene are born with some symptoms. “There was still room for improvement,” says Richard Finkel, a clinical neuroscientist at St. Jude Children’s Research Hospital in Memphis, Tennessee, who led the study.

genetics, DNA, genes, genome, heredity, genetic variation, mutation, epigenetics, genetic disorders, genomics, genetic engineering, CRISPR, molecular biology, gene expression, inheritance, genetic sequencing, biotechnology, population genetics, personalized medicine, genetic research,

#Genetics #DNA #Genes #Genome #Heredity #GeneticVariation #Mutation #Epigenetics #GeneticDisorders #Genomics #GeneticEngineering #CRISPR #MolecularBiology #GeneExpression #Inheritance #GeneticSequencing #Biotechnology #PopulationGenetics #PersonalizedMedicine #GeneticResearch

International Conference on Genetics and Genomics of Diseases

Visit: genetics-conferences.healthcarek.com

Award Nomination: genetics-conferences.healthcarek.com/award-nomination/?ecategory=Awards&rcategory=Awardee

Award registration: genetics-conferences.healthcarek.com/award-registration/

For Enquiries: contact@healthcarek.com

Get Connected Here
---------------------------------
---------------------------------
in.pinterest.com/Dorita0211
twitter.com/Dorita_02_11_
facebook.com/profile.php?id=61555903296992
instagram.com/p/C4ukfcOsK36
genetics-awards.blogspot.com/
youtube.com/@GeneticsHealthcare

DNA deletion disease syndromes

Characterizing the spectrum of mitochondrial DNA deletion disease syndromes

Researchers from the Mitochondrial Medicine Program at Children's Hospital of Philadelphia (CHOP) have better characterized a spectrum of what were classically considered discrete mitochondrial DNA deletion disease syndromes. The findings offer new insights into genetic causes, potential symptoms, and disease progression, and may inform future clinical trial development. The findings were published today in the journal Genetics in Medicine.

Mitochondrial disease refers to a group of disorders that affect the mitochondria, which are tiny compartments present in almost every cell of the body that generate most of our energy. Certain forms of mitochondrial disease – Pearson syndrome, Kearns-Sayre syndrome (KSS) and chronic progressive external ophthalmoplegia (CPEO) – are each caused by single large-scale mitochondrial DNA (mtDNA) deletions (SLSMD), which involve the loss of a large segment within the small DNA genome that is found exclusively in the mitochondria.

While the genetic cause of these SLSMD syndromes is similar, the affected tissues and clinical presentations can vary wildly. Pearson syndrome is typically diagnosed in infancy due to growth failure and anemia; KSS might develop as progressive multi-system symptoms during mid-childhood; and CPEO typically presents in adults with eye muscle movement problems. Understanding the natural history study of these rare diseases is particularly challenging because so few patients are diagnosed in any stage and some cases can lead to early death.

To better understand SLSMD's molecular and clinical scope, researchers compiling information and data from 30 known cases seen at CHOP between 2002 and 2020 was performed using modern techniques for analyzing electronic medical records to more quickly and nimbly conduct a retrospective natural history study.

"Although these are the three named syndromic phenotypes in the spectrum SLSMD syndromes, the spectrum is actually broader and includes patients whose symptoms do not meet any of their strict diagnostic criteria," said first study author Rebecca Ganetzky, M.D., an attending physician in Mitochondrial Medicine and the Director of Mitochondrial Biochemical Diagnostic Test Development at CHOP. "This retrospective natural history study was designed more accurately inform the spectrum of clinical presentation for SLSMD disorders. This will enable future clinical trials to enroll a greater range of patients and evaluate a wider range of clinical endpoints that effectively describe symptom and quality of life effects in meaningful ways to patients across the disease spectrum."

Many of these patients share certain molecular details. For example, this study found that a recurrent deleted region within the gene MT-ND5 occurred in 96% of SLSMD patients, regardless of their eventual clinical phenotype, which tended to evolve from one category to the next in certain patients over time. Additionally, the biomarker peptide growth differentiation factor 15 (GDF-15) was highly elevated in all SLSMD patients in this study, regardless of clinical features. Higher levels in blood of SLSMD heteroplasmy– a phenomenon unique to mtDNA reflecting the presence of both normal and deleted genomes in a patient – correlated with earlier age of disease onset. As a patient's age increased, greater fatigue and lower quality of life were reported.

This study was supported in part by an investigator-initiated sponsored research award from Minovia Therapeutics and from the Children's Hospital of Philadelphia Mitochondrial Medicine Frontier Program.

DNA deletion, genetic mutation, genome editing, chromosomal aberration, gene loss, genetic disorder, DNA repair, genetic variation, CRISPR-Cas9, genetic recombination, hereditary disease, DNA sequencing, mutation analysis, exon deletion, genomic instability, structural variation, genetic abnormality, frameshift mutation, molecular genetics, pathogenic mutation,

#DNADeletion #GeneticMutation #GenomeEditing #ChromosomalAberration #GeneLoss #GeneticDisorder #DNARepair #GeneticVariation #CRISPRCas9 #GeneticRecombination #HereditaryDisease #DNASequencing #MutationAnalysis #ExonDeletion #GenomicInstability #StructuralVariation #GeneticAbnormality #FrameshiftMutation #MolecularGenetics #PathogenicMutation

International Conference on Genetics and Genomics of Diseases

Visit: genetics-conferences.healthcarek.com

Award Nomination: genetics-conferences.healthcarek.com/award-nomination/?ecategory=Awards&rcategory=Awardee

Award registration: genetics-conferences.healthcarek.com/award-registration/

For Enquiries: genetics@healthcarek.com

Get Connected Here
---------------------------------
---------------------------------
in.pinterest.com/Dorita0211
twitter.com/Dorita_02_11_
facebook.com/profile.php?id=61555903296992
instagram.com/p/C4ukfcOsK36
genetics-awards.blogspot.com/
youtube.com/@GeneticsHealthcare