December 21, 2024

Wonder Drug

Scientists Finally Crack 60-Year Mystery Behind Diabetes ‘Wonder Drug’ Metformin



The antidiabetic drug metformin, widely prescribed for managing Type 2 diabetes, has long been recognized for its capacity to reduce blood glucose levels, attenuate inflammation, and slow tumor progression. Despite its widespread use for over 60 years, the precise molecular mechanisms underlying its effects have remained unclear.

A recent study from Northwestern Medicine, published in Science Advances, sheds light on this longstanding question by identifying mitochondrial complex I as a primary target of metformin.
Targeting Mitochondria To Regulate Blood Sugar

Metformin exerts its glucose-lowering effects by disrupting energy production within the mitochondria, a key organelle responsible for cellular metabolism. The study demonstrates that the drug inhibits mitochondrial complex I, a crucial component of the mitochondrial electron transport chain. This disruption impairs cellular energy production in select cell types, including those implicated in disease, while sparing healthy cells.

“While millions of people take metformin, its mechanism of action has remained enigmatic,” said Navdeep Chandel, senior author and professor of medicine and biochemistry at Northwestern University Feinberg School of Medicine. “This research provides clear evidence that metformin lowers blood glucose levels by targeting mitochondrial complex I.”

The Experimental Approach: Using Genetically Engineered Mice


The team conducted experiments on genetically engineered mice expressing NDI1, a yeast-derived enzyme that mimics the function of complex I but is resistant to metformin. By comparing glucose levels in mice treated with metformin, the study uncovered the following key findings:

In wild-type mice, metformin significantly reduced blood glucose levels.
Mice expressing NDI1 exhibited reduced sensitivity to metformin, with a less pronounced decrease in blood glucose levels.

The partial resistance observed in NDI1-expressing mice suggests additional pathways may contribute to metformin’s glucose-lowering effects.

This work builds on earlier research showing metformin’s ability to inhibit mitochondrial complex I in cancer cells, potentially slowing tumor growth.

Metformin’s Broad Applications and Future Research

Metformin’s benefits extend beyond diabetes management. Research has linked it to:Cancer therapy: Inhibiting complex I in cancer cells.

Inflammation reduction: Alleviating pollution-induced inflammation in studies with mice.

COVID-19 outcomes: Preliminary studies suggest metformin might improve survival rates.

These results strongly implicate mitochondrial complex I as a critical target of metformin in glucose regulation. Furthermore, earlier research from the Chandel lab demonstrated that metformin’s inhibition of complex I also contribute to its anti-cancer effects in cells expressing metformin transporters.

“We believe the diverse effects of metformin—ranging from glucose regulation to inflammation reduction and potential anti-cancer properties—can be partially explained by its inhibition of mitochondrial complex I,” Chandel said. He emphasized the need for further research to corroborate these findings and explore additional mechanisms.

A Historic Drug With a Modern Understanding

Metformin, derived from compounds in the French lilac plant, has been a cornerstone of diabetes management since its introduction more than six decades ago. Its low cost and efficacy make it a first-line therapy for millions of patients worldwide. In the United States, it is frequently used alongside newer antidiabetic medications, including semaglutides like Ozempic and Mounjaro.

The drug’s multifaceted effects have prompted numerous hypotheses about its mechanisms over the years. However, many of these theories have lacked definitive experimental evidence or consensus within the scientific community.

What Lies Ahead

The identification of mitochondrial complex I as a primary target of metformin opens new avenues for research. By elucidating the specific pathways involved in its action, scientists can refine therapeutic strategies for diabetes and potentially extend metformin’s application to other diseases.

“Metformin’s interaction with mitochondrial complex I offers a cohesive explanation for its effects across multiple conditions,” Chandel noted. “This understanding provides a foundation for further exploration into how targeting mitochondria can enhance human health.”

This study not only resolves a decades-old question about metformin’s mechanism of action but also underscores the potential of mitochondrial biology as a focal point for developing novel therapeutic interventions.

innovative medicine, breakthrough therapy, pharmacological marvel, targeted treatment, next-generation drug, therapeutic agent, medical innovation, FDA approval, revolutionary cure, clinical trials, life-saving medication, drug efficacy, pharmaceutical development, chronic disease management, advanced therapy, biotechnology, precision medicine, health transformation, drug discovery, patient outcomes

#WonderDrug, #MedicalBreakthrough, #PharmaceuticalInnovation, #RevolutionaryTreatment, #DrugDiscovery, #LifeChangingMedicine, #AdvancedTherapy, #PrecisionMedicine, #InnovativeHealthcare, #ClinicalTrials, #HealthCareSolutions, #TargetedTherapies, #NextGenMedicine, #TherapeuticAdvancement, #CureInnovation, #BiotechSolutions, #LifeSaver, #ChronicDiseaseTreatment, #MedicalAdvances, #FutureOfHealth

International Conference on Genetics and Genomics of Diseases 
at No comments:

December 20, 2024

SCD Patients Treatment

SCD patients free of VOEs after treatment with gene-editing therapy


Nearly all the patients with severe sickle cell disease (SCD) who were treated with renizgamglogene autogedtemcel (reni-cel) remained free of vaso-occlusive events (VOEs) for up to two years, new data from the Phase 1/2/3 RUBY clinical trial shows.

The treatment also increased total hemoglobin levels and was well tolerated, according to a company press release from Editas Medicine, the developer of the gene-editing therapy.

Data from 28 patients was presented at the Annual Meeting and Exposition of the American Society of Hematology (ASH) in a poster presentation titled, “Reni-Cel, an Investigational AsCas12a Gene-Edited Cell Medicine, Led to Sustained Hemoglobin Normalization and Increased Fetal Hemoglobin in Patients with Severe Sickle Cell Disease Treated in the RUBY Trial.” The presentation was made by Rabi Hanna, MD, from the department of Pediatric Hematology, Oncology, and Blood and Marrow Transplantation at Cleveland Clinic Children’s hospital.

SCD is caused by mutations in the HBB gene that lead to the production of a defective version of adult hemoglobin, the protein that transports oxygen in red blood cells. As a result, the cells take on a sickle-like shape and die prematurely (hemolysis), often causing patients to develop anemia, one of the most common SCD symptoms.

People with SCD may also experience VOEs, which include painful vaso-occlusive crises (VOCs) and other complications that occur when sickled cells obstruct blood vessels and block blood flow, depriving tissues of oxygen.

Reni-cel, formerly EDIT-301, was designed to increase the production of fetal hemoglobin (HbF), a type that’s typically made during early fetal development and is more efficient at carrying oxygen than the protein’s adult version.

What is reni-cel gene-editing therapy?

The treatment involves collecting hematopoietic stem cells — which are capable of giving rise to all types of blood cells — from a patient’s bone marrow and modifying them to introduce genetic changes that mimic those naturally found in people with hereditary persistence of fetal hemoglobin, a benign condition where HbF production persists into adulthood.

After a course of chemotherapy to destroy stem cells in the bone marrow and make room for the modified ones, the engineered stem cells are infused back into the patient via a stem cell transplant. These modified stem cells are then expected to give rise to red blood cells that can produce HbF, which should reduce red blood cell sickling and the frequency of VOEs.

The Phase 1/2/3 RUBY trial (NCT04853576) is evaluating the safety and efficacy of a single infusion of reni-cel in patients with severe SCD, which is defined as those having at least two severe VOEs that require medical attention per year in the two years before entering the study. The patients, who researchers described as “broadly representative of the overall population of patients with severe SCD,” were a mean age of 26.1 and more than half were women (53.6%). In the two years before enrolling they had a mean of 4.6 severe VOEs a year.

Consistent with previous data, all but one patient remained free of VOEs from the time they received treatment, with the follow-up ranging from about 21 days to 25.5 months, or about two years. Moreover, after six months, the patients’ total hemoglobin levels increased to a mean of 13.8 g/dL, and HbF levels reached 48.1%. The mean percentage of HbF-producing red blood cells increased early and was maintained above 90% from four months post-treatment up to the last follow-up.

Also, mean corpuscular fetal hemoglobin, the average fetal hemoglobin levels, in HbF-producing red blood cells increased early and remained above the sickling threshold of 10 picograms per cell through the last follow-up. Markers of hemolysis reduced or normalized six months after treatment and generally remained the same at the last evaluation.

Sustained clinically meaningful improvements in patient-reported outcomes were also reported after treatment across several domains, including pain, physical function, social roles and activities.

Transplanted stem cells survived and expanded within the bone marrow in all the evaluated patients. The treatment was also well tolerated, with the therapy’s safety profile being consistent with a stem cell transplant and chemotherapy conditioning with busulfan.

Two serious adverse events were considered to be possibly related to reni-cel: a case of cute respiratory distress syndrome and another of eosinophilic gastroenteritis, a gastrointestinal disease.

Sickle Cell Disease, hemoglobinopathy, sickle hemoglobin, red blood cell deformity, vaso-occlusion, chronic hemolysis, anemia, oxidative stress, genetic mutation, hemoglobin S, pain crisis, hydroxyurea therapy, bone marrow transplant, disease management, erythrocyte dysfunction, ischemia-reperfusion injury, pediatric hematology, genetic counseling, stroke in SCD, organ damage, fetal hemoglobin, quality of life, inflammation in SCD, sickle cell trait, patient advocacy, public health,

#SickleCellDisease #SCD #Hemoglobinopathy #RedBloodCells #VasoOcclusion #Anemia #GeneticDisorder #HemoglobinS #PainCrisis #Hydroxyurea #BoneMarrowTransplant #DiseaseManagement #PediatricHematology #GeneticCounseling #StrokeSCD #ChronicHemolysis #FetalHemoglobin #OrganDamage #Inflammation #SickleCellTrait #OxidativeStress #PatientAdvocacy #PublicHealth #QualityOfLife #SickleCellAwareness

at No comments:

December 19, 2024

Rare Genetic Disorders

For kids with rare genetic disorders, customized CRISPR treatments offer hope


Lucy Landman was born with a very rare genetic disorder that causes severe intellectual disability, weak muscles and seizures, among other symptoms.

"She is expected to very much never be able to live independently, likely never be potty trained, likely never speak," says Geri Landman, Lucy's mother.

Lucy, who is now 3 years old, has trouble with coordinating her muscles. She "walks like she's drunk most of the time," Landman says. "It's hard to watch your child suffer. And Lucy does, some days, suffer a lot."

There are only a handful of kids in the world with Lucy's disorder, which is called PGAP-3 CDG. There's no way to treat it.

In principle, CRISPR, the gene-editing technique that enables scientists to easily make very precise changes in genes, could be a godsend for patients like Lucy. CRISPR can edit the pairs of genetic letters, or bases, that make up DNA.

"We're lucky that both of her mutations — the one that she gets from me and the one she gets from my husband — are what we call base-editable," says Landman, a pediatrician who lives outside San Francisco.

That means her mutations are good candidates for CRISPR, which could be used to "kind of cut out the wrong base pair and put back in the right one," she says.

Landman says she also feels lucky to live in 2024 when CRISPR treatments are "a legitimate possibility."

The rarest diseases get overlooked by drugmakers

But Lucy's disorder affects too few people to attract the millions of dollars necessary to find out if CRISPR could work.

"When Lucy was diagnosed, I asked a bunch of my basic science friends who work at Genentech and all these other big companies in the Bay Area and I said, "Can't we just CRISPR this? This seems like it's so feasible,'" Landman says. "And they were like: 'No one's working on this yet, Geri.'"

So Landman started a foundation to try to change that by raising money to research single-gene disorders like her daughter's.

One day, while out fundraising at a farmer's market, she bumped into Fyodor Urnov, who works at the Innovative Genomics Institute at the University of California, Berkeley. The institute was started by Jennifer Doudna, who shared a Nobel Prize for helping discover CRISPR.

Urnov and his colleagues are trying to help kids suffering from rare disorders like Lucy's. There are thousands of such conditions that affect millions of patients.

"The for-profit sector is focusing on conditions, such as sickle cell disease, such as cancer, which are commercially viable because there are just enough people with them," Urnov says.

The problem is, "that leaves 99.5% of folks outside of the big building that says, 'Come here, be healed by CRISPR' because the commercial viability is not there even though the technical feasibility is right in our hands."

A 'cookbook' for CRISPR treatments

So Urnov, as well as scientists at other universities, including the University of Pennsylvania and Harvard, are trying to develop a template for groups of rare conditions that are similar enough that a gene-editing treatment for one could be easily adapted for others.

"We are building a set of recipes and approaches for how to switch from one disease to another and not take four years and $10 million to do that," Urnov says.

The approach from one patient to the next would be essentially identical except for the specific genetic letters that are edited, he says. That way each case wouldn't necessarily have to go through a long, expensive approval process at the Food and Drug Administration.

"The central idea is that cookbook will have been reviewed by the Food and Drug Administration," Urnov says. And then scientists could approach the agency and essentially say: "FDA: We have a severely ill child with four months to live. Here is the cookbook for how to make the CRISPR on demand. We'd like to use that cookbook."

Hopefully, he says, the answer would be: " 'Yes. We understand. Please proceed.' That's the goal."

It's an ambitious goal. But others say it could work.

"CRISPR is very much like a razor blade handle and a razor," says Dr. Peter Marks, the director of the Center for Biologics Evaluation and Research, which regulates gene editing at the FDA.

"Much of CRISPR — the razor-blade handle part — is going to be the same over and over again. And so we just need to focus on the razor-blade portion, which could be different [for different rare diseases] and yet fit on that same razor," Marks says.

Urnov has already started editing some of Lucy's cells in his lab to show that CRISPR could help her and other kids with similar mutations.

Geri Landman is hopeful that maybe, someday that could help her daughter Lucy.

"And the question is: 'If we do that at age 3 or age 5 or age 7 can we cure some of the other features of her disease? Does she cognitively improve? Does she learn to speak in that way?'" Landman says. "That's certainly the hope."

CRISPR, gene editing, rare genetic disorders, personalized medicine, genetic therapies, customized treatments, DNA repair, genome editing tools, rare diseases, pediatric genetics, CRISPR-Cas9, precision medicine, gene therapy advancements, inherited diseases, genetic engineering, gene mutations, targeted therapies, gene repair, genetic innovation, personalized healthcare, genetic research, hereditary conditions, DNA editing, breakthrough treatments, customized medicine, pediatric patients,

#CRISPR #GeneEditing #RareDiseases #GeneticDisorders #PersonalizedMedicine #DNARepair #GenomeEditing #RareGenetics #CRISPRCas9 #PediatricGenetics #PrecisionMedicine #GeneTherapy #GeneticInnovation #HereditaryDisorders #TargetedTherapies #DNAEditing #GeneRepair #RareGenomics #ChildrensHealth #RareDiseaseHope #CustomTreatments #FutureMedicine #GeneticsForKids #Genomics #HealthcareInnovation

at No comments:

December 18, 2024

Scientists Identify Genes

Scientists Identify Genes That Shape People's Teeth


A group of genes drive the shape of each person’s teeth, including at least one gene inherited from Neanderthals, a new study published Dec. 12 in Current Biology found.

There are 18 sets of genes that influence the size and shape of teeth, 17 of which had not been previously linked to tooth development, researchers reported.

This includes a gene believed to be inherited from Neanderthals due to interbreeding with ancient humans.

“We have now identified numerous genes that impact the development of our teeth, some of which are responsible for differences between ethnic groups,” researcher Kaustubh Adhikari, a statistical geneticist with the University College London, said in a news release from the university.

These genetic revelations help inform scientists' understanding of human evolution, but they’ll also potentially contribute to better dental health, said lead researcher Qing Li, a postdoctoral researcher with Fudan University in China.

“Some of the genes that contribute to the normal variation of tooth dimensions among healthy people can also contribute to pathogenic variation, such as teeth failing to grow in or other dental health conditions,” Li said.

“We hope that our findings could be useful medically, if people with particular dental problems could undergo genetic tests to help in diagnosis, or if some dental anomalies could be treated one day with gene therapies,” Li added.

For the study, researchers analyzed data from nearly 900 volunteers in Colombia of mixed European, Native American and African ancestry.

The data included dental crown measurements derived from 3D scans of dental plaster casts taken from the participants, which researchers compared with each person’s genetic information.

The Neanderthal gene variant linked to teeth was only found in people of European descent, researchers said. Carriers of the variant have thinner incisors, the eight teeth at the front of the mouth that are best at biting into food.

Another gene known to impact incisor shape in East Asian people, EDAR, also appears to influence the width of teeth in all humans.

Overall, people of European descent also had smaller teeth, researchers noted.

“Our findings did not shed light on whether the genes that identify tooth shape were selected in evolution due to particular advantages to dental health, so it’s possible that the genes may have been selected due to the influences they have in other areas, with tooth shape differences resulting as a side effect, said researcher Andres Ruiz-Linares, a professor of human genetics with University College London.

dental genetics, tooth shape, gene identification, enamel development, genetic traits, dental morphology, odontogenesis, dental enamel, tooth formation, hereditary dental traits, dental evolution, tooth structure, dentition pattern, craniofacial genetics, dental anomalies, tooth genes, genetic variants, tooth mineralization, dental tissue, dental phenotypes, dental disorders, gene mapping, genetic inheritance, tooth development, genome-wide studies, dental gene expression,

#DentalGenetics #ToothShape #Genetics #EnamelDevelopment #Odontogenesis #ToothGenes #DentalMorphology #HereditaryTraits #DentalAnomalies #DentalScience #GeneticTraits #ToothFormation #DentalHealth #GenomeStudies #ToothDevelopment #CraniofacialGenetics #DentalResearch #GeneMapping #DentalEvolution #DentalBiology #ToothGenetics #DentitionPattern #GeneExpression #GeneticInheritance #ToothStructure

International Conference on Genetics and Genomics of Diseases 




For Enquiries: genetics@healthcarek.com 

Get Connected Here 
--------------------------------- 
--------------------------------- 
at No comments:

December 16, 2024

Genetic Behavior Changes

Genetic Mechanism Links Emotional Experiences to Behavior Changes



Researchers have identified a genetic mechanism that regulates behavioral adaptations to emotional experiences by forming R-loops, unique RNA:DNA structures that activate target genes. The study focused on NPAS4, a gene implicated in stress and drug addiction, showing how blocking R-loops prevents maladaptive behaviors like cocaine seeking and stress-induced anhedonia in mice.

This mechanism demonstrates how emotional experiences influence brain circuits by altering gene expression through enhancer RNA. The findings could pave the way for RNA-based therapies to treat psychiatric disorders linked to stress and substance use.R-Loop Role: R-loops form RNA:DNA structures to activate genes like NPAS4 during emotional experiences.
Behavioral Impact: Blocking R-loops in brain regions prevents drug-seeking and stress-induced behaviors in mice.

Therapeutic Potential: Insights could guide the development of RNA-based treatments for mood and substance use disorders.

Source: Medical University of South Carolina

A team of neuroscience researchers at the Medical University of South Carolina reports in Science the discovery of a new genetic regulatory mechanism involved in behavioral adaptations to emotional experiences in a preclinical model.

Although such adaptations are crucial for survival, they can become problematic in patients with certain psychiatric disorders.

Understanding the genetic changes that lead to maladaptive behaviors may help scientists to develop better RNA therapies to treat brain disorders.

The research team included Makoto Taniguchi, Ph.D., assistant professor in the Department of Neuroscience, Christopher Cowan, Ph.D., professor and chair of the Department of Neuroscience, and Rose Marie Akiki, an M.D.-Ph.D. student at MUSC.

With funding from the National Institutes of Health and a pilot grant from the South Carolina Clinical & Translational Research Institute, the researchers set out to understand how clinically relevant emotional experiences, including chronic stress and drug use, lead to long-lasting changes in behavior.

Ultimately, their findings show that loss of this genetic regulatory mechanism leads to reduced drug seeking and increased resilience to stress in mice.

“By understanding this process, we hope to get better insights into how changes in the brain can lead to maladaptive changes in behavior,” said Cowan. “We could also improve our fundamental understanding of how the brain works and how emotions and emotionally relevant experiences help to shape brain circuits.”

Scientists have long known that what we experience can cause changes in our brain, thereby altering how we behave. But how exactly do those changes occur? Well, it begins with our genes.

All cells within an individual contain essentially the same genes, but different genes can be turned on at different times.

This variability allows our bodies to adapt to a changing environment. Importantly, well over half of the human genome is devoted to producing a specific type of regulatory molecules that help to control when and where critical protein-coding genes are turned on.



These regulatory molecules, known as long non-coding RNAs (lncRNAs), have been found to differ in people with depression and substance use disorders.

The MUSC researchers focused on long non-coding enhancer RNA (Inc-eRNA), a specific type of lncRNA that interacts with the regulatory region of target genes. Upon binding to specific genes, Inc-eRNA can form unique structures, known as R-loops, to help to govern those genes.

The MUSC team looked at a gene called NPAS4, which is implicated in both stress-induced anhedonia, or lack of joy in activities that were once pleasurable, and drug-induced relapse.

Their study provides the first evidence for the role of R-loops in governing behavioral changes induced by emotional experiences.

R-loops can help to turn on specific genes by forming an RNA:DNA “sandwich” in regulatory regions of a target gene.

In the case of the NPAS4 gene, R-loops appear to help to bring the enhancer region, which includes instructions for turning on a gene and is located at a distance, together with the main body of the gene, including the important gene promoter region, and this allows the gene to be turned on in response to an experience.

“By bringing the enhancer and promoter together in space and time, R-loops seem to be facilitating their interaction and driving the response to turn on a gene,” said Cowan.

In response to emotional experiences, some people struggle more than others, and this may result in the development of maladaptive behaviors. For example, the death of a loved one is a very difficult experience to process that could lead some individuals to develop depression, while others are able to make peace with their loss.

The specific behaviors the researchers analyzed in mice were cocaine seeking and a response to chronic stress, as these are clinically relevant responses to particularly emotional experiences.

When the researchers blocked the formation of R loops in front of the NPAS4 gene in the region of the brain known as the nucleus accumbens, they found that mice did not show a preference for cocaine.

When a similar manipulation was performed in the prefrontal cortex, mice did not develop behaviors mimicking stress-induced anhedonia.

These findings suggest that lnc-eRNAs, and associated R-loops, at the NPAS4 gene are an important process in the brain by which emotional experiences can produce behaviors associated with substance use or mood disorders.

“You need a change in the genetic basis of how everything is working, what is being transcribed, what is being formed in the cell to form stronger neural circuits that underlie behavior,” said Akiki.

behavior changes, behavioral adaptation, habit formation, behavior modification, lifestyle changes, mental health, emotional well-being, motivation, resilience, cognitive-behavioral therapy, stress management, self-regulation, decision-making, mindfulness, goal setting, personality development, behavior triggers, emotional intelligence, social behavior, psychological flexibility, behavioral interventions, peer influence, coping strategies, neuroplasticity, habit breaking, self-awareness,

#BehaviorChange #MentalHealth #Habits #WellBeing #BehavioralAdaptation #LifestyleChange #Motivation #Mindfulness #CBT #StressManagement #GoalSetting #EmotionalIntelligence #SocialBehavior #Resilience #SelfRegulation #CopingStrategies #Neuroplasticity #Psychology #HabitBreaking #EmotionalWellness #BehavioralInterventions #SelfAwareness #MentalResilience #DecisionMaking #BehaviorTriggers

at No comments:

December 14, 2024

Genetic basis of Fertility

The genetic basis of fertility, family and longevity



Led by researchers from the University of Oxford’s Leverhulme Centre for Demographic Science and the University of Iceland, the review explores how genetic variations can explain differences in reproductive health and longevity.

The study provides the most comprehensive review of male and female genetic discoveries of reproductive traits to date, and provides new insights into how our DNA affects when we have children, the timing of menopause, and even how that is connected to how long we live.

Genes at the heart of reproduction

Using the GWAS Catalog, an online database of Genome Wide Association Studies (GWAS), the researchers identified 159 genetic studies and 37 key genes that are linked to reproductive traits such as age at first childbirth, menopause timing, and hormones such as follicle-stimulating hormone (FSH) and testosterone. These findings suggest that genetic factors play a significant role in broader health outcomes as well as influencing fertility.

One gene in particular, FSHB (follicle-stimulating hormone subunit beta), was found to be associated with eleven different reproductive outcomes. This gene helps regulate when menstruation begins and when menopause occurs, highlighting its role in reproductive health and ageing. The review also revealed connections between these reproductive genes and rare genetic disorders, showcasing how DNA impacts both fertility and overall health.

Senior lead author Professor Melinda Mills, Director of the Leverhulme Centre for Demographic Science and Oxford Population Health’s Demographic Science Unit said ‘As more people delay parenthood to later ages, it is important to understand the genetic factors underpinning an individual’s reproductive health and fertility window. Our study brings together research on the genetics of reproduction to reveal common genes across traits and insights beyond fertility that are inherently linked to health, body mass index (BMI) and obesity, hormone sensitive cancers, and even psychiatric and behavioural traits.’

First author Dr Stefanía Benónísdóttir, Postdoctoral Researcher at the Leverhulme Centre for Demographic Science and University of Iceland, said ‘By consolidating this research, we offer a clearer picture of how genetic factors shape reproductive health. This is essential for advancing healthcare, especially when it comes to infertility and reproductive ageing.’

Longevity, cancer, obesity risk and reproductive traits

The review explored the connections between reproductive genes and longevity, finding that genes like ESR1 (estrogen receptor 1) are linked to reproductive traits as well as to cancer risk. For example, starting puberty earlier or experiencing later menopause may increase the risk of hormone-sensitive cancers like breast cancer, but these same traits are associated with a longer lifespan. The FTO (fat mass and obesity associated) gene - previously found to have strong associations with BMI, obesity risk and type 2 diabetes - was also linked to multiple different reproductive traits. Understanding these genetic links is critical as more people choose to delay having children, making reproductive health and ageing even more intertwined.

Male fertility

While previous research has focused on female reproductive health, the study reviews what is known about the genetics of male fertility. Genes like DNAH2 are shown to play a role in both testosterone levels and sperm function, making it crucial for male reproductive health.

Co-author Vincent Straub, DPhil student at the Leverhulme Centre for Demographic Science and Oxford Population Health, said ‘Male reproductive health is critical to overall fertility but often under-researched. By exploring the genetics of male infertility, we can uncover new insights and potential treatments for those struggling with reproductive challenges.’

Genetics across generations

The review examined how genetic changes affect future generations. As parents age, they accumulate de novo mutations - new, spontaneous genetic changes that can be passed to their children. These mutations can have significant effects on the health and development of offspring, previously discovered by senior co-author Professor Augustine Kong.

This comprehensive review offers crucial insights into how our genes shape reproductive health, fertility, and longevity, providing a foundation for more personalised healthcare approaches that could improve outcomes for individuals and families across generations.

fertility genetics, family inheritance, longevity genes, reproductive health, genetic diversity, genetic determinants, fertility biomarkers, aging genes, heritability, epigenetics of reproduction, genetic mutations, reproductive lifespan, genetic influences, family genetics, mitochondrial DNA, genome-wide association studies, hormonal pathways, DNA methylation, gene-environment interaction, Y-chromosome analysis, ovarian function, genetic predisposition, telomere length, fertility decline, evolutionary genetics, maternal genetics

#FertilityGenes #GeneticInheritance #LongevityGenes #ReproductiveHealth #GeneticDiversity #AgingBiology #FamilyGenetics #Epigenetics #Heritability #GenomicStudies #MitochondrialDNA #HormonalPathways #DNAResearch #GeneEnvironment #ReproductiveLifespan #GeneticHealth #Telomeres #FertilityDecline #YChromosome #MaternalGenes #EvolutionaryGenetics #GeneticPredisposition #LongevityResearch #ReproductionScience #GeneticMarkers

at No comments:

December 13, 2024

Genetic research

Genetic research could help your favorite beans withstand climate change


Black beans, kidney beans, pinto beans … most of the beans you see in the grocery store today are varieties of a species known as the common bean.

And in many parts of the world, growing common beans is getting harder as climate change causes increasingly hot, dry weather.

So researchers have been studying another species called the tepary bean. Tepary beans are native to parts of the Sonoran Desert and grow well in hot, dry regions.

Urrea: “They are able to grow under drought and high heat conditions.”

Carlos Urrea is a dry edible bean breeding specialist at the University of Nebraska. He and his team have been working to identify the genes that give tepary beans drought and heat tolerance as well as disease resistance. And they’re working to breed these traits into common beans.

Urrea: “Now we are able to move genes from the tepary beans to the common beans.”

His team has created new varieties that are being field-tested in drought-prone regions such as Nebraska, California, Puerto Rico, Uganda, and Tanzania.

He says these new varieties have the potential to help feed people who rely on beans as a critical food source and where food scarcity is a growing concern as the climate warms.

#Genetics #Genomics #DNA #RNA #Epigenetics #Heredity #GeneticDisorders #CRISPR #GenomeEditing #GeneTherapy #PopulationGenetics #MolecularBiology #Bioinformatics #GeneticEngineering #PersonalizedMedicine #GeneticCounseling #GeneExpression #Epigenome #Mutation #GeneticDiversity #SyntheticBiology #Pharmacogenomics #EvolutionaryGenetics #Transcription #Translation

International Conference on Genetics and Genomics of Diseases 




For Enquiries: genetics@healthcarek.com 

Get Connected Here 
--------------------------------- 
--------------------------------- 
at No comments:

December 12, 2024

Wheat Genetics

Research published in Nature opens door for advancements in MSU wheat genetics


As defined by Nature, genome refers to, “the complete set of genetic information in an organism.” Modern bread wheat has three genomes: the A genome, B genome and D genome. When the D genome hybridized with the A and B genomes roughly 8,000-11,000 years ago to create what is now modern bread wheat, the process subsequently restricted wheat’s genetic diversity.

By studying the genetic makeup of Tausch’s goatgrass and other wild wheat relatives, which are described in the paper as “genetic reservoirs,” breeders and geneticists can use the knowledge to improve modern bread wheat through the discovery and enhancement of genes — such as the one examined in this project Olson found during his doctoral research at Kansas State University.

“My colleagues and I cloned a disease resistance gene I identified during my work at Kansas State University,” Olson said. “As a Ph.D. student, I did the genetic mapping and transferred this gene to modern bread wheat, but it was through this work that we were able to differentiate the gene from others in the same chromosome region and get the actual sequence for this disease resistance gene.”

The project was led by the King Abdullah University of Science and Technology in Saudi Arabia. Results were published in Nature on Aug. 14, 2024.

The team analyzed and sequenced 493 different Tausch’s goatgrass accessions — genetic material representing specific genotypes collected in distinct geographies — which gave rise to 46 unique genome assemblies that were studied.

Olson said the information gathered from evaluating the genome assemblies will advance how the MSU Wheat Breeding and Genetics Program goes after traits of interest when developing new wheat varieties.

“This research will help us identify individual genes controlling qualitative traits, including specific resistance to disease or pests,” Olson said. “On top of that, however, these wild wheat relatives have traits that are important for climate resiliency, heat and drought tolerance and other characteristics critical for modern wheat production.

“Those specific traits weren’t evaluated in this paper, but this paper positions us to use these genomes to unlock those traits in modern bread wheat. Once we bring those genes into wheat, we can start evaluating the effects on qualities like grain yield and biomass production.”

wheat genetics, MSU, Nature, yield enhancement, disease resistance, CRISPR, climate adaptability, sustainable agriculture, food security, genome mapping, drought resistance, pest control, biofortification, precision agriculture, phenotyping, epigenetics, gene-editing, protein synthesis, crop rotation, biodiversity, soil health, hybrid breeding, root architecture, nitrogen efficiency, carbon sequestration.

#WheatGenetics #MSU #NatureResearch #SustainableAgriculture #FoodSecurity #CRISPR #PrecisionFarming #CropScience #DroughtResistance #GeneEditing #SoilHealth #Biodiversity #ClimateAdaptability #GenomeMapping #DiseaseResistance #HybridBreeding #PestControl #Biofortification #PathogenResistance #NitrogenEfficiency #CarbonSequestration #AgInnovation #PlantScience #GlobalNutrition #Phenotyping.

International Conference on Genetics and Genomics of Diseases 




For Enquiries: genetics@healthcarek.com 

Get Connected Here 
--------------------------------- 
--------------------------------- 
at No comments:

December 11, 2024

Genetic code deploys cancer

Genetic code deploys cancer mafia, new targeted drug gives them an offer they can’t refuse



Findings from groundbreaking research could forge a path for new treatments that are able to target tumors in the first, most curable stages of disease.

group of scientists at VCU Massey Comprehensive Cancer Center have revealed a new genetic code that acts like a cancer ringleader, recruiting and deploying a gang of tumor cells to incite a biological turf war by invading healthy organs and overpowering the normal cells. This discovery — published today, Dec. 9, in Nature Biotechnology — could unveil an entirely different understanding of the origins of cancer within the body, as well as offer groundbreaking insight into new treatment strategies that could target the growth of tumors in their earliest stages.

The study authors have also developed an intravenous therapy that empowers healthy cells to mount an immune response and build up a defensive resistance against these invading tumor cells. This treatment has already been proven effective in ovarian tumors, but the implications of this research could be universal to all cancer types.

“We identified a biological mechanism through which cancer cells gaslight the human body, altering the genome of the host cells and forcing them into a state of low fitness, creating an enormous advantage for the cancer to take over,” said study author Esha Madan, Ph.D., member of the Cancer Biology research program at Massey and an assistant professor in the Department of Surgery at the Virginia Commonwealth University School of Medicine. “We have developed a monoclonal antibody which can stop this process. There are many targeted drugs already available to treat tumors, but for the first time ever we are enabling our entire body, beyond the immune system, to fight back against cancer.”

Through previous research, Madan, study co-author Rajan Gogna, Ph.D., and their collaborators found that, in addition to the immune system, the human body has an inherent neighborhood watchdog function, where healthy cells detect abnormal cells and alert other normal cells to effectively prevent invasive cells from doing any damage. However, somewhere along the way, this function fails during cancer progression.

A cancer cell’s journey can take many years before it becomes a tumor that is diagnosed in the clinic, needing time to take up residence in an organ and multiply. When cancer cells show up in an organ, they participate in a territorial standoff with normal cells through a process called cell competition. They have the ability to communicate with each other using “fitness fingerprints,” proteins on the cell surface that act as messengers between the two groups by using a series of codes.

Every cell in the human body carries a code on its surface. Gogna and Madan identified a previously unknown protein called the Flower gene, which is responsible for delivering a fitness code that can be expressed in two forms: Flower-Win and Flower-Lose. Like the names imply, cells expressing the Flower-Win code are more dominant and overpower cells expressing the Flower-Lose code. Essentially, when they encounter each other, a ‘winner’ cell will kill a ‘loser’ cell and occupy its space in an organ. Cancer cells were found to express high levels of the Flower-Win code, where normal cells more often expressed the Flower-Lose code.

“Cancer basically functions as a local bully, and these Flower proteins give it the tools to behave like that,” said Gogna, member of the Developmental Therapeutics research program at Massey and assistant professor in the Department of Human and Molecular Genetics at the VCU School of Medicine. “When they overexpress this Flower-Win code, they intimidate the host cells by signaling that they are the bosses, flashing their genetic weapons to communicate to the cellular neighborhood that they’re here to survive and thrive.”

The Massey researchers have patented a monoclonal antibody, a laboratory-manufactured drug administered by infusion that specifically targets and binds to the Flower gene, which has significantly reduced cancer growth and improved survival in models of ovarian cancer. The drug works by masking the expression of the Flower-Lose code among healthy cells, allowing for the body to effectively continue its regular biological neighborhood watchdog routine and turn away invading tumor cells.

“We know that early detection is paramount to favorable patient outcomes,” said study co-author Robert A. Winn, M.D., cancer center director and Lipman Chair in Oncology at Massey. “The findings from this groundbreaking research could forge the path for new treatments that are able to target tumors in the first, most curable stages of disease.”

Looking ahead, the study authors hope to be able to investigate the efficacy of this antibody in clinical trials, and many other reputable institutions have already expressed interest in partnering with Massey on a multicenter effort.

Although the monoclonal antibody has shown promise in ovarian cancer, the researchers believe the study findings will have broad implications for treating all types of tumors in their earliest forms.

“The collaboration between VCU School of Medicine and Massey holds unlimited value and impact. Our scientists continue to make progress by confronting and studying the hard questions,” said study co-author Arturo P. Saavedra, M.D., Ph.D., dean of the VCU School of Medicine. “Though it can often seem daunting, risky and expensive, innovative research performed by our teams has shown that no challenge is too big when it comes to advancing the health of our community and our nation."



at No comments:

December 10, 2024

Cystic Fibrosis

Current landscape of Cystic Fibrosis gene therapy



Cystic fibrosis is a life-threatening disease that is caused by mutations in CFTR, a gene which encodes an ion channel that supports proper function of several epithelial tissues, most critically the lung. Without CFTR, airway barrier mechanisms are impaired, allowing for chronic, recurrent infections that result in airway remodeling and deterioration of lung structure and function. Small molecule modulators can rescue existing, defective CFTR protein; however, they still leave a subset of people with CF with no current disease modifying treatments, aside from lung transplantation. Gene therapy directed to the lung is a promising strategy to modify CF disease in the organ most associated with morbidity and mortality. It is accomplished through delivery of a CFTR transgene with an airway permissive vector. Despite more than three decades of research in this area, a lung directed gene therapy has yet to be realized. 

There is hope that with improved delivery vectors, sufficient transduction of airway cells can achieve therapeutic levels of functional CFTR. In order to do this, preclinical programs need to meet a certain level of CFTR protein expression in vitro and in vivo through improved transduction, particularly in relevant airway cell types. Furthermore, clinical programs must be designed with sensitive methods to detect CFTR expression and function as well as methods to measure meaningful endpoints for lung structure, function and disease. Here, we discuss the current understanding of how much and where CFTR needs to be expressed, the most advanced vectors for CFTR delivery and clinical considerations for detecting CFTR protein and function in different patient subsets.

Cystic fibrosis (CF) is the most common autosomal recessive disease and affects approximately 40,000 people in the United States and 80,000 people worldwide (Cromwell et al., 2023). It is caused by variants in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) which encodes a chloride channel that is found on the membrane of many cell types in the body (Riordan, 1989; Saint-Criq and Gray, 2017). Lack of CFTR function at the apical surface of secretory epithelial tissues such as the lung and pancreas is the cause of morbidity, although many organs are affected including the reproductive system, intestine, liver, bone, and kidney. In the classic CF disease progression, pulmonary complications as a result of thick inspissated mucus, chronic bacterial colonization and ongoing lung destruction are the principal cause of death. The average life span of people with CF (PwCF) has drastically improved over the years to mid to late 40s (mid-50s if born after 2018) but has historically struggled to get beyond childhood without therapeutic intervention (Castellani and Assael, 2017; McBennett et al., 2022). A person with CF experiences an annual decline in lung function of 1%–2%, and without a lung transplantation or disease-modifying therapy, 80% will succumb to respiratory failure (Lyczak et al., 2002; Leung et al., 2020). Significant understanding of the genetic basis for CF and the resulting pathophysiology has led to the development of CFTR modulators, small molecules that correct and/or potentiate dysfunctional CFTR protein to clinically meaningful output with daily medication (Middleton et al., 2019). 

However, there is still great unmet need for PwCF that are unable to benefit from modulators due to their specific CFTR variant, intolerable side effects or lack of access (10%–20% of patients) (Hubert et al., 2017; Burgener and Moss, 2018). Therefore, a gene therapy for CF which introduces a functional CFTR gene into patients’ cells could treat >4,000 patients in the US unable to use modulators. Despite identification of the genetic cause more than three decades ago, CFTR gene therapy has yet to progress beyond clinical trials due to a lack of sustained efficacy and prolonged lung function improvements in patients. New insights into the expression and function of CFTR in relevant cell types, novel delivery methods for introducing CFTR into target airway cells and more sensitive measurements for lung function in the clinic, particularly in young children or those patients with milder disease most likely to benefit from early CFTR intervention, are promising steps toward a clinically approved CF gene therapy.

Cystic Fibrosis, CFTR gene, lung infections, mucus buildup, respiratory system, genetic disorder, chloride channels, pulmonary disease, pancreatic insufficiency, chronic cough, digestive problems, CFTR protein, sweat test, genetic mutation, airway clearance, lung function, Pseudomonas aeruginosa, inflammation, antibiotic therapy, enzyme supplementation, gene therapy, newborn screening, life expectancy, personalized medicine, CFTR modulators.

#CysticFibrosis, #CFTR, #GeneticDisorder, #LungHealth, #MucusBuildup, #RespiratoryCare, #ChronicIllness, #PancreaticInsufficiency, #GeneticMutation, #SweatTest, #AirwayClearance, #PulmonaryDisease, #LungFunction, #CFResearch, #GeneTherapy, #NewbornScreening, #CFTreatment, #LifeExpectancy, #PersonalizedMedicine, #CFCommunity, #Inflammation, #AntibioticTherapy, #CFTRModulators, #EnzymeSupplementation, #RareDisease.
at No comments:

December 09, 2024

Nano-Vaccine Effective

Needle-Free: New Nano-Vaccine Effective Against All COVID-19 Variants


A new nano-vaccine developed by TAU and the University of Lisbon offers a needle-free, room-temperature-storable solution against COVID-19, targeting all key variants effectively.

Professor Ronit Satchi-Fainaro’s lab at Tel Aviv University’s Faculty of Medical and Health Sciences has collaborated with Professor Helena Florindo’s lab at the University of Lisbon to develop a novel nano-vaccine for COVID-19. This nano-vaccine, a 200-nanometer particle, effectively trains the immune system against all common COVID-19 variants, performing as well as existing vaccines.

Unlike other vaccines, it is conveniently administered as a nasal spray and does not require a cold supply chain or ultra-cold storage. These distinctive features pave the way for vaccinating populations in developing countries and the future development of simpler, more effective, and less expensive vaccines. The groundbreaking study was featured on the cover of the prestigious journal Advanced Science.

Development and Design of the Nano-Vaccine

Prof. Satchi-Fainaro explains: “The new nano-vaccine’s development was inspired by a decade of research on cancer vaccines. When the COVID-19 pandemic began, we set a new goal: training our cancer platform to identify and target the coronavirus. Unlike Moderna and Pfizer, we did not rely on full protein expression via mRNA. Instead, using our computational bioinformatics tools, we identified two short and simple amino acid sequences in the virus’s protein, then synthesized them, and encapsulated them in nanoparticles.” Eventually, this nano-vaccine proved effective against all major variants of COVID-19, including Beta, Delta, Omicron, etc.

Benefits of the Nano-Vaccine: Needle-Free Administration

“Our nano-vaccine offers a significant advantage over existing vaccines because it is needle-free and administered as a nasal spray,” notes Prof. Satchi-Fainaro. “This eliminates the need for skilled personnel such as nurses and technicians to administer injections, while also reducing risks of contamination and sharp waste. Anyone can use a nasal spray, with no prior training.”

Advantages in Storage and Shipping

Another major advantage of the revolutionary nano-vaccine is its minimal storage requirements. Moderna’s sensitive mRNA-based vaccine must be kept at -20°C and Pfizer’s at -70°C, generating great logistic and technological challenges, such as shipping in special aircraft and ultra-cold storage – from the factory to the vaccination station.

Prof. Satchi-Fainaro’s novel synthetic nanoparticles are far more durable and can be stored as a powder at room temperature. “There’s no need for freezing or special handling,” she says. “You just mix the powder with saline to create the spray. For testing purposes (as part of the EU’s ISIDORe (Integrated Services for Infectious Disease Outbreak Research) feasibility program) we shipped the powder at room temperature to the INSERM infectious diseases lab in France. Their tests showed that our nano-vaccine is at least as effective as Pfizer’s vaccine.”

Future Implications and Expanding Applications

These important advantages—ease of nasal administration and regular storage and shipping — pave the way towards vaccinating at-risk populations in low-income countries and remote regions, which existing vaccines are unable to reach. Moreover, the novel platform opens the door for quickly synthesizing even more effective and affordable vaccines for future pandemics. “This is a plug-and-play technology,” explains Prof. Satchi-Fainaro. “It can train the immune system to fight cancer or infectious diseases like COVID-19. We are currently expanding its use to target a range of additional diseases, enabling the rapid development of relevant new vaccines when needed.”

COVID-19 variants, SARS-CoV-2, Omicron, Delta variant, Alpha variant, Beta variant, Gamma variant, Lambda variant, Mu variant, XBB, BA.2, BA.5, EG.5, pandemic, coronavirus mutations, spike protein, viral transmission, vaccine efficacy, immune escape, public health, antiviral treatments, genome sequencing, global surveillance, variant of concern, outbreak response, epidemiology,

#COVID19Variants, #SARSCoV2, #Omicron, #DeltaVariant, #AlphaVariant, #BetaVariant, #GammaVariant, #LambdaVariant, #MuVariant, #XBB, #BA2, #BA5, #EG5, #Pandemic, #CoronavirusMutations, #SpikeProtein, #VaccineEfficacy, #ImmuneEscape, #PublicHealth, #AntiviralTreatments, #GenomeSequencing, #GlobalSurveillance, #VariantOfConcern, #OutbreakResponse, #Epidemiology

at No comments:

December 07, 2024

Genetics Event

International Conference on Genetics and Genomics of Diseases 



at No comments:

Myeloma Therapy

Genes Highlight Who'll Benefit From Multiple Myeloma Therapy


Genetic tests can show which patients with the blood cancer multiple myeloma should respond to targeted therapy, a new study finds.

A special six-gene pattern can help predict who are more likely to respond well to Venclexta (venetoclax), a pill that promotes natural cell death among cancer cells, researchers said.

“By knowing which patients might benefit the most, we can customize treatments to improve their chances of success,” said researcher Alessandro Lagana, an assistant professor of oncological sciences at the Icahn School of Medicine at Mount Sinai, in New York City.

Multiple myeloma is a cancer of blood plasma cells, according to the American Cancer Society. About 35,780 new cases of multiple myeloma are expected to be diagnosed in 2024, and it will kill about 12,540 U.S. adults.

Venclexta keeps cancer cells from dodging apoptosis, the body process that causes old or damaged cells to self-destruct.

Multiple myeloma cells carry a protein called BCL-2 that keeps the cell from triggering apoptosis. Venclexta inhibits BCL-2, restoring natural cell death for these cancer cells.

The U.S. Food and Drug Administration approved Venclexta in 2018, but up to now it’s been unclear which patients would most benefit from the drug.

For this study, researchers analyzed the genetics of 58 patients treated with Venclexta between 2017 and 2021.

They discovered a specific genetic pattern “with higher scores being consistently associated with less favorable responses,” the research team wrote.

“Doctors could use genetic testing to choose the best candidates for venetoclax treatment,” Lagana said in a Icahn news release.

Researchers also found that Venclexta worked best when paired with a CKD7 inhibitor, another type of drug that promotes natural cell death.

“Combining venetoclax with CDK7 inhibitors might help more patients respond positively,especially those who might not respond well to venetoclax alone,” Lagana said. “For patients, this research means someday they could receive more personalized treatment plans based on their genetic information, leading to better outcomes.”

Researchers next plan to confirm their findings in a larger group of patients, and to test the combined use of Venclexta and CDK7 inhibitors in clinical trials.

The new study was published in December issue of the journal Blood Neoplasia.

Multiple myeloma, myeloma therapy, plasma cell neoplasm, monoclonal antibodies, proteasome inhibitors, immunomodulatory drugs, CAR-T cell therapy, bispecific antibodies, autologous stem cell transplant, minimal residual disease, amyloidosis, lenalidomide, bortezomib, daratumumab, pomalidomide, selinexor, elotuzumab, ixazomib, Venetoclax, dexamethasone, alkylating agents, cytokine release syndrome, relapse, refractory myeloma, personalized medicine.

#MultipleMyeloma, #MyelomaTherapy, #CancerTreatment, #PlasmaCellNeoplasm, #MonoclonalAntibodies, #ProteasomeInhibitors, #Immunotherapy, #CAR_T, #StemCellTransplant, #MinimalResidualDisease, #Amyloidosis, #Lenalidomide, #Bortezomib, #Daratumumab, #Pomalidomide, #Selinexor, #Elotuzumab, #Ixazomib, #Venetoclax, #Dexamethasone, #OncologyResearch, #RelapseMyeloma, #RefractoryMyeloma, #PrecisionMedicine, #CancerAwareness.

at No comments:
Subscribe to: Posts (Atom)

Wonder Drug

Scientists Finally Crack 60-Year Mystery Behind Diabetes ‘Wonder Drug’ Metformin The antidiabetic drug metformin, widely prescribed for mana...

  • Fruitful innovation
    Fruitful innovation: Transforming watermelon genetics with advanced base editors The development of new adenine base editors (ABE) and adeni...
  • Genetic factors with clinical trial stoppage
    Genetic factors associated with reasons for clinical trial stoppage Many drug discovery projects are started but few progress fully through ...
  • Asexual Ants maintain Genetic Diversity
    How do asexual ants maintain genetic diversity? It’s commonly accepted wisdom that genetic diversity is vital for the survival of a species...