Breaking News
December 12, 2018 - Aspirin could reduce HIV infections in women
December 12, 2018 - Sacrificial immune cells alert body to infection
December 12, 2018 - Low-salt diet may be more beneficial for females than males
December 12, 2018 - Major soil organic matter compound battles chronic wasting disease
December 12, 2018 - Findings may open up new ways to treat dwarfism and other ER-stress-related conditions
December 12, 2018 - New computational model provides clearer picture of shape-changing cells’ structure and mechanics
December 12, 2018 - 10 Facts on Patient Safety
December 12, 2018 - Poorest dying nearly 10 years younger than the rich in ‘deeply worrying’ trend for UK
December 12, 2018 - Innovative care model for children with ASD reduces use of behavioral drugs in ED
December 12, 2018 - Spending time in and around Hong Kong’s waters linked to better health and wellbeing
December 12, 2018 - Simple measures to prevent weight gain over Christmas
December 12, 2018 - Research advances offer hope for patient-tailored AML treatment
December 12, 2018 - Researchers discover a ‘blind spot’ in atomic force microscopy
December 12, 2018 - Sprayable gel could help prevent recurrences of cancer after surgery
December 12, 2018 - SLU researchers explore how fetal exposure to inflammation can alter immunity in newborns
December 12, 2018 - How do patients want to discuss symptoms with clinicians?
December 12, 2018 - Zinc chelation may be able to deliver drug to insulin-producing cells
December 12, 2018 - Brigham researchers develop automated, low-cost tool to predict a woman’s ovulation
December 12, 2018 - Some people with Type 2 diabetes may be testing their blood sugar more often than needed
December 12, 2018 - Slow-growing type of glioma may be vulnerable to immunotherapy, suggests study
December 12, 2018 - Study provides new information regarding microRNA function in cellular homeostasis of zebrafish
December 12, 2018 - Study provides new understanding of mysterious ‘hereditary swelling’
December 12, 2018 - Researchers shed new light on how to combat Shiga and ricin toxins
December 12, 2018 - Pregnant Women Commonly Refuse Vaccines
December 12, 2018 - Drug treatment could offer new hope for some patients with brain bleeding
December 12, 2018 - Health care financial burden of animal-related injuries is growing, study says
December 12, 2018 - Macrophage cells could help repair the heart following a heart attack, study finds
December 12, 2018 - Researchers develop new system for efficiently producing human norovirus
December 12, 2018 - New artificial intelligence-based system to differentiate between different types of cancer cells
December 11, 2018 - Brazilian professors propose guidelines for therapeutic use of melatonin
December 11, 2018 - Healthy Lifestyle Lowers Odds of Breast Cancer’s Return
December 11, 2018 - New research identifies two genes linked to serious congenital heart condition
December 11, 2018 - NIH Director talks science, STEM careers with preteens
December 11, 2018 - Disabling a Cellular Antivirus System Could Improve Gene Therapy
December 11, 2018 - New tool swiftly provides accurate measure of patients’ cognitive difficulties
December 11, 2018 - NICE releases new guidelines for diagnosis and management of COPD
December 11, 2018 - Without Obamacare penalty, think it’ll be nice to drop your plan? Better think twice
December 11, 2018 - Researchers capture high-resolution X-ray and NMR image of key immune regulator
December 11, 2018 - Natural flavonoid is effective at treating leishmanisis infections, study shows
December 11, 2018 - Avoidant grievers unconsciously monitor and block mind-wandering contents, study shows
December 11, 2018 - Study identifies how hantaviruses infect lung cells
December 11, 2018 - Improving PTSD care through genetics
December 11, 2018 - Dermatology providers show interest in recommending cannabinoids to patients
December 11, 2018 - Researchers to study effects of electroconvulsive therapy on Alzheimer’s patients with aggression
December 11, 2018 - Four dried fruits have lower glycemic index than starchy foods, study finds
December 11, 2018 - Optimization of drug dose sizes can reduce pharmaceutical wastage
December 11, 2018 - Ultrarestrictive opioid prescribing strategy linked with reduction in number of pills dispensed
December 11, 2018 - PET scans to optimize tuberculosis meningitis treatments and personalize care, study finds
December 11, 2018 - Researchers aim to identify and target high blood pressure indicators
December 11, 2018 - Researchers identify immune cell subset that may drive chronic inflammation
December 11, 2018 - Ezogabine treatment reduces motor neuron excitability in ALS patients, study shows
December 11, 2018 - One implant, two prices. It depends on who’s paying.
December 11, 2018 - Standardizing feeding practices improves growth trends for micro-preemies
December 11, 2018 - COPD Tied to Obesity in Male, Female Never-Smokers
December 11, 2018 - Flossing: Information for Caregivers
December 11, 2018 - Does breastfeeding hormone protect against type 2 diabetes?
December 11, 2018 - Educating future doctors to prescribe physical activity for their patients
December 11, 2018 - Krystal 2000 microplate design improves fluorescence and luminescence measurement
December 11, 2018 - FDA clears mobile medical app to help increase retention in recovery program for opioid use disorder
December 11, 2018 - Overcoming Challenges in High-Speed Centrifugation Experiments
December 11, 2018 - Study shows link between neighborhoods’ socioeconomic status and dietary choices
December 11, 2018 - Lower BMI before obesity surgery predicts greater post-operative weight loss, study finds
December 11, 2018 - Obesity May Be Driving Rise in Uterine Cancers
December 11, 2018 - Antioxidants may prevent cognitive impairment in diabetes
December 11, 2018 - Study discovers link between meditation and how individuals respond to feedback
December 11, 2018 - Researchers identify potential diagnostic tool for Alzheimer’s disease
December 11, 2018 - Oral cancer prognostic signature identified
December 11, 2018 - How Can I Find Out What Caused My Miscarriage?
December 11, 2018 - Novel personalized medicine tool for assessing inherited colorectal cancer syndrome risk developed
December 11, 2018 - Study uncovers 11 new genes associated with epilepsy
December 11, 2018 - Filling research gaps could help develop more disability-inclusive workplaces
December 11, 2018 - Cartilage tissue engineering brings good news for patients with cartilage defects
December 11, 2018 - Novel 3D printing workflow helps predict leaky heart valves
December 11, 2018 - Imagination can help overcome fear and anxiety-related disorders, shows study
December 11, 2018 - Are caries linked to political regime?
December 11, 2018 - Leader in Diabetes Clinical Trials Wins Naomi Berrie Award
December 11, 2018 - Scientists discover cellular mechanism that triggers pneumonia in humans
December 11, 2018 - Increasing mental health problems related to drug use in over 55’s
December 11, 2018 - High-intensity interval exercise could help combat cognitive dysfunction in obese people
December 11, 2018 - Annual flu shot can save lives of heart failure patients
Researchers use gene therapy that lengthens telomeres to cure pulmonary fibrosis in mice

Researchers use gene therapy that lengthens telomeres to cure pulmonary fibrosis in mice

image_pdfDownload PDFimage_print

Idiopathic pulmonary fibrosis is a potentially lethal disease associated with the presence of critically short telomeres, currently lacking effective treatment. The Telomere and Telomerase Group at the Spanish National Cancer Research Centre (CNIO) has succeeded in curing this disease in mice using a gene therapy that lengthens the telomeres. This work constitutes a “proof of concept that telomerase activation represents an effective treatment against pulmonary fibrosis,” the authors write in their publication in the journal eLife. Given that telomere shortening is also an indicator of organism ageing, Maria A. Blasco, lead author of the paper, points out that “this is the first time that pulmonary fibrosis has been treated as an age-related disease, looking for rejuvenating the affected tissues”.

“The most relevant aspect of our work is that it suggests a potentially viable and effective solution to a real clinical problem, pulmonary fibrosis, for which there is still no treatment,” says Paula Martínez, co-first author of the paper. “The only approved treatments for pulmonary fibrosis up-to-date have no curative effects, as they target a symptom and not the cause of fibrosis. Our therapy is based on correcting the molecular cause of pulmonary fibrosis in patients with short telomeres, introducing into the cells of damaged lung tissue the only enzyme capable of lengthening telomeres, telomerase. “

Telomeres are protein structures located at the ends of each chromosome; like caps, they protect the integrity of the chromosome when the cell divides. But telomeres only fulfill their protective function if they are long enough; when they shorten too much, the damaged cells cease to divide preventing tissue regeneration. Short telomeres are associated with aging -as age increases, cells accumulate more divisions and more telomeric shortening- and also with several diseases. Pulmonary fibrosis, which affects around 8,000 people in Spain, is one of them.

In lung fibrosis, the lung tissue develops scars that cause a progressive loss of respiratory capacity. Environmental toxins play an important role in its origin, but it is known that there must also be telomeric damage for the disease to appear. Patients with pulmonary fibrosis have short telomeres whether the disease is hereditary -it runs into the family- or not. The most likely explanation is that when the telomeres become too short, the damaged cell activates a ‘repair program’ that induces scar formation that leads to fibrosis.

The best animal model available

The CNIO Telomere and Telomerase Group, led by Blasco, decided to address the problem about five years ago, starting with the development of an animal model that faithfully reproduces the human disease. The most widely used model until then was to apply bleomycin into the mouse lungs to induce damage, in an attempt to reproduce the environmental insult. However, in these animals the disease goes into remission in a few weeks and there is not telomere shortening.

The CNIO researchers sought after a mouse model in which the environmental damage synergized to that produced by short telomeres, that is what happens in human pulmonary fibrosis. They succeeded in 2015, when they already indicated their next goal in their research work: “This is an essential model to test therapeutic strategies based on the activation of telomerase [the enzyme that repairs the telomeres]”, they wrote in the journal Cell Reports.

Their current publication shows that activating the telomerase enzyme to lengthen the telomeres in the lung tissue may constitute an effective therapeutic strategy to treat human pulmonary fibrosis. It has proven so in mice. Only three weeks after treatment, the sick animals “showed improved lung function and less inflammation and fibrosis” -the authors write in eLife-; two months after the treatment, the fibrosis had “improved or disappeared”.

A genetic driver

The treatment consisted of introducing the telomerase gene into the lung cells using gene therapy. The researchers first modified a virus innocuous to humans (known as vectors) so that their genetic material incorporated the telomerase gene, and then injected those vectors into the animals. The animals received a single injection of this genetic taxi.

As Juan Manuel Povedano, co-first author of the paper, explains, “we observe that telomerase gene therapy reverses the fibrotic process in mice, which suggests that it could be effective in human patients, opening a new therapeutic opportunity towards the treatment of this disease”. Povedano is now a postdoctoral researcher at the Southwestern Medical Center at the University of Texas, USA.

The work has been carried out in collaboration with the gene therapy expert Fàtima Bosch, from the Autonomous University of Barcelona, ??with whom the first steps will also be taken to bring this therapy closer to its use in humans. “The strategy devised by the CNIO group is very encouraging,” says Bosch; “although we are still far from reaching the clinic, we are already generating gene therapy vectors for human therapy”.

The basis of this work is the hypothesis that age-associated diseases can be treated by targeting the molecular and cellular processes of ageing, specifically telomere shortening. In 2012, Blasco and her group generated mice that not only lived longer but also showed improved health by treating them with telomerase. Her work since then has aimed to develope this therapy to specifically treat age-associated diseases and telomere syndromes.

They have obtained positive results in the treatment of heart infarct, aplastic anemia and, now, pulmonary fibrosis. In the case of heart infarct, research to bring therapy to the clinic is already underway, in collaboration with the Fàtima Bosch’s group and Francisco Fernández-Avilés, Head of the Cardiology Service at the Hospital General Universitario Gregorio Marañón.

Source:

https://www.cnio.es/ing/publicaciones/cnio-researchers-cure-lung-fibrosis-in-mice-with-a-gene-therapy-that-lengthens-telomeres

Tagged with:

About author

Related Articles