Breaking News
January 16, 2019 - A new brain imaging study challenges the dominant theoretical model of autism spectrum disorders
January 16, 2019 - GoFundMe CEO: ‘Gigantic Gaps’ In Health System Showing Up In Crowdfunding
January 16, 2019 - Induced neuronal cells derived from fibroblasts are similar to neurons in the brain
January 16, 2019 - New study finds link between childhood abuse and suicide in later life
January 16, 2019 - Lifestyle and health factors that are good for the heart can also prevent diabetes
January 16, 2019 - Scientists take another step in understanding bacteria that cause Salmonella epidemic
January 16, 2019 - Look to Your Aunts, Uncles and Parents for Clues to Your Longevity
January 16, 2019 - Study finds ADHD drugs are unlikely to cause cardiac damage in children who take them
January 16, 2019 - Call The Midwife! (If The Doctor Doesn’t Object)
January 16, 2019 - Changes in hippocampal structural connectivity differentiate responders of electroconvulsive therapy
January 16, 2019 - Study sheds light on the deadly venom of Mojave rattlesnakes
January 16, 2019 - University of Nebraska to develop new drugs that prevent and counteract effects of radiation exposure
January 16, 2019 - Sugar-based stent makes precarious sewing process easier
January 16, 2019 - FDA-approved drug hampers cancer metastasis in animal model, shows study
January 16, 2019 - Childhood body composition may play a role in future respiratory health
January 16, 2019 - Outdated commissioning methods are failing mental health services in the UK, reveals report
January 16, 2019 - Unconventional immune cells trigger disturbed cytokine production in human spondyloarthritis
January 16, 2019 - Patients Turn To GoFundMe When Money And Hope Run Out
January 16, 2019 - Researchers develop novel viral identification method
January 16, 2019 - Study proposes improvements in pharmacological study of cognitive function enhancers in schizophrenia
January 16, 2019 - Study points to potential new biomarker and drug target for amyotrophic lateral sclerosis
January 16, 2019 - Differences in geographic origin of genes may affect mitochondrial function
January 16, 2019 - Study analyzes vaccine-preventable infections in children who receive solid organ transplants
January 16, 2019 - MiRagen Announces New Clinical Data in Patients With Three Different Types of Blood Cancers Treated With Cobomarsen
January 16, 2019 - Scientists uncover why knee joint injury leads to osteoarthritis
January 16, 2019 - Salk team uses new model to study health effects of AMP-activated protein kinase
January 16, 2019 - Research reveals novel approach to suppressing chemotherapy-induced tumor growth
January 16, 2019 - Researchers reveal how fasting leads to better overall health
January 16, 2019 - Deprivation and neglect in early childhood have impact on cognitive functioning in adolescence, shows study
January 16, 2019 - Training Students to use Imaging Techniques: NMR and EPR
January 16, 2019 - Nerve transfer surgery restores arm movement in children with acute flaccid myelitis
January 16, 2019 - Exelixis Announces U.S. FDA Approval of Cabometyx (cabozantinib) Tablets for Previously Treated Hepatocellular Carcinoma
January 16, 2019 - DNA vaccine reduces both toxic proteins linked to Alzheimer’s
January 16, 2019 - Even in the U.S., poor women often can't afford tampons, pads
January 16, 2019 - One time use of Marijuana could affect teen brains finds study
January 16, 2019 - Persistent Opioid Use High in Head, Neck Cancer Patients
January 16, 2019 - Questions to ask your doctor about post pregnancy care: MedlinePlus Medical Encyclopedia
January 16, 2019 - Neurons with good housekeeping are protected from Alzheimer’s
January 16, 2019 - Is mindfulness worthy of all the hype?
January 16, 2019 - Physical Activity, Any Type or Amount, Cuts Health Risk from Sitting
January 16, 2019 - New understanding in the evolution of human feet
January 15, 2019 - AHA: New Cholesterol Guidelines Put Ethnicity in the Spotlight
January 15, 2019 - Different brain areas linked to smoking and drinking
January 15, 2019 - Henry Marsh shares insights into neurosurgery and more at Dean’s Lecture Series
January 15, 2019 - Want to Live Longer? For Just 30 Minutes a Day, Do Anything Else But Sit
January 15, 2019 - The Current issue of “The view from here” is concerned with Targets
January 15, 2019 - Plain packaging sparked tobacco price rises, new study finds
January 15, 2019 - Sedentary lifestyles can be unhealthy, physical activity can lower risk
January 15, 2019 - Gut microbiome may help prevent development of cow’s milk allergy
January 15, 2019 - Lesbian, gay and bisexual individuals more likely to suffer severe substance use disorders
January 15, 2019 - New England Journal of Medicine Publishes Positive Results of the Pivotal Trial of Cablivi (caplacizumab) for Rare Blood Clotting Disorder
January 15, 2019 - Levels of inflammatory marker (CRP) linked to housing type and tenure
January 15, 2019 - Three gifts I’m glad I gave myself in 2018
January 15, 2019 - Columbia’s Pediatrics Department Names New Vice Chairs, Expands Leadership
January 15, 2019 - US FDA Accepts Regulatory Submissions for Review of Tafamidis to Treat Transthyretin Amyloid Cardiomyopathy
January 15, 2019 - Staying fit can cut your risk of heart attack by half
January 15, 2019 - Vitamin D supplements are of no gain to those over 70, study shows
January 15, 2019 - Scientists create comprehensive new method to predict breast cancer risk
January 15, 2019 - Research shows connection between social media use and impaired risky decision-making
January 15, 2019 - FDA Approves Expanded Use of Adacel (Tdap) Vaccine for Repeat Vaccination
January 15, 2019 - Treating spinal pain with replacement discs made of ‘engineered living tissue’ moves closer to reality
January 15, 2019 - Providers Walk ‘Fine Line’ Between Informing And Scaring Immigrant Patients
January 15, 2019 - Outcomes Poorer for Medicaid Beneficiaries With STEMI
January 15, 2019 - Decorative Products on Foods Can Be Unsafe
January 15, 2019 - A dream of sustainable surgery in Uganda
January 15, 2019 - Study shows how herpes viruses and tumors have learned to manipulate the same ancient RNA
January 15, 2019 - Common Heart, Diabetes Meds May Help Ease Mental Illness
January 15, 2019 - Stress and trauma in earliest years linked to reduced hippocampal volume in adolescence
January 15, 2019 - Scientists identify endogenous activator of sigma-1 receptors in human cells
January 15, 2019 - MAR treatments unlikely to be cause of premature or low birth weight babies
January 15, 2019 - Parental CPTSD increases transmission of trauma to offspring of Tutsi genocide survivors
January 15, 2019 - High-fat diets shown to increase blood pressure
January 15, 2019 - New institute for food safety to be established in Netherlands
January 15, 2019 - Keele University researchers receive £2.4 million grant to help reduce overprescribing of opioids
January 15, 2019 - Synthetic compound reverses mutant p53 aggregate accumulation, study shows
January 15, 2019 - First elder care robot tested in a WSU smart home apartment
January 15, 2019 - Oxford researchers explore relationship between technology use and adolescent mental health
January 15, 2019 - From microbiome research to healthier and sustainable foods
January 15, 2019 - How coaching moms and dads improves infants’ language skills
January 15, 2019 - Precision health approach tapped to identify causes of poverty
Study advances gene therapy for glaucoma

Study advances gene therapy for glaucoma

image_pdfDownload PDFimage_print
In an effort to improve gene transfer to treat the blinding disease glaucoma, the front of an untreated eye (left) is compared to an eye (right) pretreated with a gene delivery enhancer. The green marker reveals the expression of a new gene in the trabecular meshwork, which drains fluid from the eye and is usually blocked in glaucoma. The green band resulting from gene transfer is denser and wider in the enhancer-treated eye. Credit: Curtis Brandt/Paul Kaufman, University of Wisconsin-Madison

While testing genes to treat glaucoma by reducing pressure inside the eye, University of Wisconsin-Madison scientists stumbled onto a problem: They had trouble getting efficient gene delivery to the cells that act like drains to control fluid pressure in the eye.

Genes can’t work until they enter a cell.

Glaucoma, one of the most common blinding diseases, is caused by excess pressure inside the eye, usually due to a clog in the fluid drain. “Most glaucoma can be treated with daily drug treatment,” says Paul Kaufman, professor of ophthalmology and visual sciences at the University of Wisconsin-Madison. “Replacement genes could, theoretically, restore normal fluid flow for years on end, without requiring daily self-administration of eye drops that is inconvenient and may have local or even systemic side effects.”

In a study published today in the scientific journal Investigative Ophthalmology and Visual Science, Kaufman and Curtis Brandt, a fellow professor of ophthalmology and visual sciences at UW-Madison, showed an improved tactic for delivering new genes into the drain, called the trabecular meshwork.

The colleagues have been testing a vector based on feline immunodeficiency virus (FIV) to deliver the genes. Like the related human immunodeficiency virus, FIV can insert genes into the host’s DNA. The eye’s innate defenses against FIV, however, interfered with the delivery.

Virus particles contain genes wrapped in a protein coat and then a lipid membrane. After the virus enters the cell and sheds its membrane, defensive molecules from the host can “drag the virus particle to the cell’s garbage disposal, called the proteasome, where it is degraded,” Brandt says. “We wanted to know if temporarily blocking the proteasome could prevent the destruction of the gene delivery vector and enhance delivery.”

In the current study, FIV virus carrying a marker protein was placed on cells of the trabecular meshwork, with or without a chemical that blocks proteasomes.

Above a dosage threshold, the treatment roughly doubled the transfer of genes entering the target cells, Brandt says. The new genes also spread more uniformly across the meshwork tissue. Delivering more copies of the gene should give a greater therapeutic effect, opening the meshwork drain and reducing pressure inside the eye.

The present study concerns the tools for transferring genes, not the genes themselves, Brandt says. But even before the current study, he says he and Kaufman “have already identified at least two genes that could unplug the drain.”

In the long struggle to replace genes and cure disease, “eyes have been one of the big success stories,” Brandt says. A blinding eye disease called Leber’s congenital amaurosis damages the function of cells that keep the light-sensitive cells healthy; replacing the mutated genes has preserved and even improved vision in young patients. Approval for this gene therapy is now pending at the Food and Drug Administration.

To forestall danger from injecting a virus, “We take out pretty much all of the virus’ genes, so it has no chance to replicate and spread from where it’s initially injected,” says Brandt.

Although the technique does interfere with the anti-viral defense in the eye, the effect is temporary. “You encounter the drug once, then it is metabolized, and the innate inhibition is lost,” Brandt says.

“We have shown that this strategy does work in eye organ culture,” Brandt says. “Once we do further work on efficiency and identify which gene to deliver, then we are probably ready to move toward clinical trials.”


Explore further:
Genetic treatment for blindness may soon be reality

Provided by:
University of Wisconsin-Madison

Tagged with:

About author

Related Articles