Breaking News
February 15, 2019 - Disruptive behavioral problems in kindergarten linked with lower employment earnings in adulthood
February 15, 2019 - New bioengineered device enhances the production of T-cells
February 15, 2019 - HDL proteome behaves like a tiny Velcro ball that is rolling on surfaces
February 15, 2019 - Puerto Rican children more likely to have poor or decreasing use of asthma inhalers
February 15, 2019 - Quality of patient care does not improve after physician-hospital integration
February 15, 2019 - Synopsys release new software for implant design and patient-specific planning
February 15, 2019 - 6 out of 10 hip replacements last 25 years or longer
February 15, 2019 - Health Tip: What You Should Know About Antibiotics
February 15, 2019 - New research challenges medical consensus that adenoids and tonsils significantly shrink during teenage years
February 15, 2019 - Discovery of weakness in a rare cancer could be exploited with drugs
February 15, 2019 - UVA scientists find potential explanation for mysterious cell death in Alzheimer’s, Parkinson’s
February 15, 2019 - New rules requiring female athletes to lower testosterone levels are based on flawed data
February 15, 2019 - Researchers comprehensively sequence the human immune system
February 15, 2019 - Researchers study animal venoms to identify new medicines for treating diseases
February 15, 2019 - Movement of wrist bones revealed by MRI and computer modeling
February 15, 2019 - Philips introduces new premium digital X-ray room to help shorten patient wait times
February 15, 2019 - Women fare worse than men following aortic heart surgery, study finds
February 15, 2019 - High-protein and low-calorie diet helps older adults lose weight safely, shows study
February 15, 2019 - Drug microdosing effects may not measure up to big expectations
February 15, 2019 - Discharged, Dismissed: ERs Often Miss Chance To Set Overdose Survivors On ‘Better Path’
February 15, 2019 - A digitized lab environment to be showcased at smartLAB 2019
February 15, 2019 - Scientists uncover main mechanisms of fluconazole drug resistance
February 15, 2019 - New study seeks to understand how colibactin causes cancer
February 15, 2019 - Photoacoustic imaging accurately measures the temperature of deep tissues
February 15, 2019 - Large study finds no association between phthalate exposure and breast cancer risk
February 15, 2019 - New research explains presence of ‘natural’ magnetism in human cells
February 15, 2019 - Bio-Rad launches new digital PCR system and kit for monitoring treatment response in CML patients
February 15, 2019 - Scientists shed light on damaging cell effects linked to aging
February 15, 2019 - High intensity exercise may improve health by increasing gut microbiota diversity
February 15, 2019 - Apellis’ APL-2 Receives Orphan Drug Designation from the FDA for the Treatment of Autoimmune Hemolytic Anemia
February 15, 2019 - Couples creating art or playing board games release ‘love hormone’
February 15, 2019 - Glimpsing The Future At Gargantuan Health Tech Showcase
February 15, 2019 - Common herbicide found to increase the risk of lymphoma
February 15, 2019 - Over-abundance of energy to cells could increase cancer risk
February 15, 2019 - Oxford Genetics appoints Jocelyne Bath as new Chief Operating Officer
February 15, 2019 - Castration-resistant metastatic prostate cancer responds to combination of immune checkpoint inhibitors
February 15, 2019 - Large-scale clinical trial begins to study liver transplantation between people with HIV
February 15, 2019 - Cannabis use among adolescents linked with increased risk of depression in adulthood
February 15, 2019 - Fractures, head injuries common in electric scooter accidents, UCLA study finds
February 15, 2019 - Prenatal maternal depression has important consequences for infant temperament, study shows
February 15, 2019 - Stereotactic body radiotherapy effective in treating men with low- or intermediate-risk prostate cancer
February 15, 2019 - Zogenix Submits New Drug Application to U.S. Food & Drug Administration for Fintepla for the Treatment of Dravet Syndrome
February 15, 2019 - Certain birthmarks warrant quick treatment, pediatricians say
February 15, 2019 - New machine learning method predicts if atypical ductal hyperplasia will turn cancerous
February 15, 2019 - Whole-genome sequencing and sharing real-time data could limit spread of foodborne bacteria
February 15, 2019 - FDA warns doctor for illegally marketing unapproved implantable device
February 15, 2019 - New injury documentation tool may provide better evidence for elder abuse cases
February 15, 2019 - Physiological age is a better predictor of survival than chronological age, shows study
February 15, 2019 - New study reveals high success rate for hip and knee replacements
February 15, 2019 - Prenatal exposures to BPA may pose threat to human ovarian function
February 15, 2019 - Suspicious spots on the lungs of children with rhabdomyosarcoma do not behave like metastases
February 15, 2019 - Diet drinks daily could raise stroke risk says study
February 15, 2019 - Many Systematic Reviews Do Not Fully Report Adverse Events
February 15, 2019 - Seven tips to protect your child from burns
February 15, 2019 - Keynote speakers announced for CBD Expo MIDWEST
February 15, 2019 - New DNA methylation GrimAge tool allows you to predict lifespan and healthspan
February 15, 2019 - New AI-driven platform analyze how pathogens infect human cells
February 15, 2019 - Increased activity of EHMT2 gene deficient neurons could cause autism in humans
February 15, 2019 - Recurring UTIs may mask symptoms of bladder or kidney cancer
February 15, 2019 - Researchers conduct extensive comparison of drugs used in treating neuroendocrine tumors
February 15, 2019 - Depression prevention for pregnant women and new mothers – new recommendations
February 15, 2019 - AHA News: Are There Health Benefits From Chocolate?
February 15, 2019 - The involvement of the gut in Parkinson’s disease: hype or hope?
February 15, 2019 - New PET imaging agent may help measure efficacy or failure of hormone therapy for breast cancer
February 15, 2019 - Preventing infections could help combat antimicrobial resistance
February 15, 2019 - Study investigates the role of estrogen in controlling glucose homeostasis
February 15, 2019 - Exposure to chemical in weedkiller Roundup raises risk of some cancers, study finds
February 15, 2019 - Smoking and drinking during pregnancy – stigma drives women to secrecy
February 15, 2019 - Low FODMAP diet reduces stomach issues caused by exercise
February 15, 2019 - Novel approach uses small amounts of tissue to quantify PD-L1 expression levels in tumors
February 15, 2019 - Breast pumps could be transmitting asthma-causing bacteria in babies, finds study
February 15, 2019 - The Pistoia Alliance Launches Next Phase of Blockchain Project to Develop Life Science R&D Use Cases
February 15, 2019 - The search for environmental causes of Parkinson’s disease moves forward
February 15, 2019 - Women scientists inhibited by funding methods that favor men, researchers say
February 14, 2019 - Few primary care physicians lack enough knowledge of cancer treatment options
February 14, 2019 - Prime real estate is determined by previous owner in the squirrel world
February 14, 2019 - Discovery of a ‘master switch’ within the immune system
February 14, 2019 - Health officers with surgical training are a safe alternative for performing C-sections
February 14, 2019 - Researchers discover mechanism on how body’s antimicrobial shield regulates microbiome
February 14, 2019 - Scynexis Announces Positive Interim Results from Phase 3 Open-Label FURI Study, Showing Oral Ibrexafungerp’s Ability to Treat Refractory Fungal Infections and to Provide an Alternative to Long-Term IV Therapies
Study highlights potential of fetal gene therapy to prevent lethal neurodegenerative disease

Study highlights potential of fetal gene therapy to prevent lethal neurodegenerative disease

image_pdfDownload PDFimage_print

A fatal neurodegenerative condition known as Gaucher disease can be prevented in mice following fetal gene therapy, finds a new study led by UCL, the KK Women’s and Children’s Hospital and National University Health System in Singapore.

The study, published today in Nature Medicine, highlights the potential of fetal gene therapy to prevent and cure neonatal lethal neurodegenerative diseases in humans in utero.

Gaucher disease is an irreversible, inherited genetic metabolic disorder that results from not having enough glucocerebrosidase (GCase) – an enzyme that breaks down fatty chemicals called glucocerebrosides (GBA). Because the body cannot break down this chemical, the fat-laden Gaucher cells build up in the spleen, liver, bone marrow, and nervous system, causing bone disease, anaemia, fatigue, eye problems, seizures, and brain damage.

Mutations in the GBA gene, which encodes the GCase enzyme that is deficient in Gaucher disease, are also a risk factor for Parkinson’s disease.”Although the symptoms of some mild forms of Gaucher disease can be treated postnatally, more severe forms that cause early-onset, irreversible neurodegeneration are currently untreatable and are often fatal in infants. Being able to provide therapy at the earliest possible opportunity is vital in treating the brain which has a limited capacity to regenerate,” explained senior author, Dr Ahad Rahim (UCL School of Pharmacy).

Scientists used a viral vector to deliver genetic material into the brains of fetal mice carrying neuropathic Gaucher disease, caused by mutations in GBA. Mice who received the gene therapy exhibited less brain degeneration and survived considerably longer than untreated mice.

“We found that the mice who received an injection of adeno-associated virus (AAV) vector were more able to break down fatty chemicals and re-express the gene encoding an enzyme that is deficient in Gaucher disease,” said corresponding author, Dr Simon Waddingdon (UCL Institute for Women’s Health).

“The mice who received the injection in utero, lived for up to at least 18 weeks after birth compared to 15 days in untreated mice and had no signs of neurodegeneration and were fertile and fully mobile. Neonatal intervention also rescued mice but less effectively.”

Given the promising results shown in mice, the team from Singapore performed the test in non-human primates (NHP) at the early stages of pregnancy. This is the gestation when a clinical diagnosis of genetic conditions can be made, and when the immune system is more responsive to gene therapy. The research involved the use of NHPs due to their similarity to humans in the development of the central nervous system, and other organs, allowing for an accurate model to be achieved in fetal gene transfer.

The team showed that the delivery of viral vectors to the developing brain is feasible using an established clinical approach that resulted in the distribution of the transgene to the developing brain.

“Macaques and humans share a very similar neurological, immunological and physiological developmental time-line in the womb, making them accurate models for pre-clinical investigations before clinical trials can proceed. We have used a clinically relevant method to deliver the GBA gene using AAV vectors to the brain efficiently.

“This new approach will bring hope, not only for Gaucher disease, but also for other inborn errors of metabolism that can potentially be treated using fetal gene therapy,” said Associate Professor Jerry Chan, Senior Consultant, Department of Reproductive Medicine, KK Women’s and Children’s Hospital.

The team, which also involved scientists from King’s College London, Imperial College London, the University of Oxford and an international team of researchers, are now engaged with Apollo Therapeutics in developing gene therapy for Gaucher disease.

Dan Brown, Chairman of the Gauchers Association added, “The Association has been involved as part of this project from a very early stage providing the initial grant to which allowed them to begin their research and are delighted to hear of the promising results published today.”

Source:

https://www.singhealth.com.sg/

Tagged with:

About author

Related Articles