Breaking News
April 25, 2019 - Prolonged exposure therapy is more effective in treating veterans with PTSD, alcohol use disorder
April 24, 2019 - Our artificial cornea breakthrough could lead to self-assembling organs
April 24, 2019 - A Stanford black, female, gay surgery resident speaks out
April 24, 2019 - Donna Lynne on Extreme Sports, Lessons From the '60s, and Taking CUIMC to the Next Level
April 24, 2019 - Pain Clinics’ Doctors Needlessly Tested Hundreds Of Urine Samples, Court Records Show
April 24, 2019 - Researchers uncover potential clue to halt destruction of nerve cells in people with ALS
April 24, 2019 - Study uncovers reasons for poor mental health in bisexual people
April 24, 2019 - Screenings, interventions, and referrals can help adolescents overcome substance abuse
April 24, 2019 - Febrile seizures following vaccination are self-resolving and not dangerous
April 24, 2019 - Flow-UV inline UV-Visible spectrometer monitors dispersion in real time
April 24, 2019 - Rates of Marijuana Use in Cancer Patients on the Rise in U.S.
April 24, 2019 - Versatile drug may protect baby from hazards of intraamniotic infections
April 24, 2019 - Financial transparency may diminish trust in doctors, new study finds
April 24, 2019 - Calling all Riders: Velocity Extends Free Registration 
April 24, 2019 - The Homeless Are Dying In Record Numbers On The Streets Of L.A.
April 24, 2019 - Simple mobility test helps predict hospital readmission in elderly heart attack patients
April 24, 2019 - Novel fluorescence imaging system helps surgeons remove small ovarian tumors
April 24, 2019 - Uncovering the Structure of HIV Integrase to Inform Drug Discovery
April 24, 2019 - Medical Marijuana Use Rising Among Cancer Patients
April 24, 2019 - Artificial intelligence approach optimizes embryo selection for IVF
April 24, 2019 - Doctor or detective? Sleuthing mysteries in medical school
April 24, 2019 - CUIMC Community Gives Blood During Spring 2019 Columbia University Blood Drive
April 24, 2019 - Americans Overwhelmingly Want Federal Protections Against Surprise Medical Bills
April 24, 2019 - Making Laboratories More Efficient with the Most Modern LIMS on the Market
April 24, 2019 - Treating cancer patients with personalized, combination therapies improves outcomes
April 24, 2019 - Researchers engineer new molecules to help stop lung cancer
April 24, 2019 - Acupuncture can be a wonderful tool for preventing number of diseases
April 24, 2019 - Daily life disability before hip replacement may predict poor post-operative outcomes
April 24, 2019 - Study finds involuntary staying in housing estates to be a potential health risk
April 24, 2019 - Older kidney disease patients starting dialysis die at higher rates than previously thought
April 24, 2019 - Time-restricted eating shows promise for controlling blood glucose levels
April 24, 2019 - Ambiguous genitalia in newborns may be more common than previously thought
April 24, 2019 - Research provides important insight on the brain-body connection
April 24, 2019 - In 10 Years, Half Of Middle-Income Elders Won’t Be Able To Afford Housing, Medical Care
April 24, 2019 - Researchers study how E. coli clones have become major cause of drug-resistant infections
April 24, 2019 - Bacterial and fungal toxins found in popular electronic cigarettes
April 24, 2019 - Factors affecting absorption of ‘sunshine vitamin’ during spring/summer months
April 24, 2019 - Texting helps improve medication adherence, health outcomes for patients with schizophrenia
April 24, 2019 - Cochrane Review looks at different ways to use nicotine replacement therapies
April 24, 2019 - New review on relationship between COPD and Type 2 diabetes
April 24, 2019 - Brain areas linked to memory and emotion aid odor navigation in humans
April 24, 2019 - Brain stimulation reverses age-related memory loss
April 24, 2019 - Amid Opioid Prescriber Crackdown, Health Officials Reach Out To Pain Patients
April 24, 2019 - $4 million NIH award will help establish UCI Skin Biology Resource-based Center
April 24, 2019 - Cancer drugs reprogram genes in breast tumors to prevent endocrine resistance, finds study
April 24, 2019 - Combination-imaging technique provides new window into macaque brain connections
April 24, 2019 - Researchers identify new allergen responsible for allergy to durum wheat
April 24, 2019 - Researchers define role of rare, influential cells in the bone marrow
April 24, 2019 - DNA rearrangement may predict poor outcomes in multiple myeloma
April 24, 2019 - FDA Approves Skyrizi (risankizumab-rzaa) for Moderate to Severe Plaque Psoriasis
April 24, 2019 - Combination therapy might be beneficial in schizophrenia
April 24, 2019 - Blood test can help match cancer patients to early phase clinical trials
April 24, 2019 - Women tend to underreport snoring and underestimate its loudness
April 24, 2019 - Comprehensive molecular test introduced for diagnosis of malaria caused by P. vivax parasites
April 24, 2019 - New range prediction approach increases accuracy, safety and tolerability of proton therapy
April 24, 2019 - Need for Sedation Up for Regular Cannabis Users
April 24, 2019 - Lack of access to antibiotics is a major global health challenge
April 24, 2019 - New study provides better understanding on safety of deworming programs
April 24, 2019 - EEG used to detect impact of maternal stress on neurodevelopment in 2-month-old infants
April 24, 2019 - FDA Approves First Generic Naloxone Nasal Spray Against Opioid Overdose
April 24, 2019 - A new way of finding compounds that prevent aging
April 24, 2019 - Mechanical training makes synthetic hydrogels perform more like muscle
April 24, 2019 - Study provides new insights into regulatory T cells’ role in protecting against autoimmune disease
April 24, 2019 - Pregnant women with type 1 diabetes are at greater risk of preterm birth
April 24, 2019 - ‘Tummy tuck’ can be safely performed in obese patients with no increase in complications
April 23, 2019 - ‘First’ 3-D print of heart with human tissue, vessels unveiled
April 23, 2019 - Which blood-based method works best to detect TB?
April 23, 2019 - Gene therapy cures infants suffering from ‘bubble boy’ immune disease
April 23, 2019 - Chemical-sampling wristbands detect similar exposures across three continents
April 23, 2019 - Management of Residual Limb Pain
April 23, 2019 - Molecular clock influences immune cell responses
April 23, 2019 - On the importance of culture, partnerships and diversity at the Dean’s Lecture Series
April 23, 2019 - Siddhartha Mukherjee Receives Lewis Thomas Prize for Writing About Science
April 23, 2019 - Dengue mosquito poses greatest danger of spreading Zika virus in Australia
April 23, 2019 - Scientists identify 104 high-risk genes for schizophrenia
April 23, 2019 - Abdominal etching can help patients to get classic ‘six-pack abs’ physique
April 23, 2019 - Alvogen Inc. Issues Voluntary Nationwide Recall of Fentanyl Transdermal System Due to Product Mislabeling
April 23, 2019 - Skype hypnotherapy is effective treatment for IBS
April 23, 2019 - The future hope of “flash” radiation cancer therapy
April 23, 2019 - Bicycling, Recycling, and Beyond: Public Safety to Host Shred Fest and Bike-to-Campus Day 
RNAi therapy mitigates preeclampsia symptoms

RNAi therapy mitigates preeclampsia symptoms

image_pdfDownload PDFimage_print
High magnification micrograph of hypertrophic decidual vasculopathy, as seen in pregnancy-induced hypertension. Credit: Wikipedia

A collaboration of scientists from the University of Massachusetts Medical School, Beth Israel Deaconess Medical Center and Western Sydney University, have shown that an innovative new type of therapy using small interfering RNAs (siRNA) can temper the symptoms of preeclampsia in an animal model. The research, led by Anastasia Khvorova, Ph.D., and Melissa Moore, Ph.D., of UMass Medical School’s RNA Therapeutics Institute and Ananath Karumanchi, MD, of Beth Israel and Harvard Medical School—suggests that RNA interference therapy could be a potential strategy for the treatment of preeclampsia in humans.

“For women with preeclampsia, being able to carry a pregnancy for just a few more weeks can make a huge difference in the health of the baby,” said Dr. Khvorova, professor of RNA therapeutics. “Thanks to rapid advances in siRNA, we’ve developed an siRNA that displays the potential to allow women with preeclampsia to extend their pregnancy from 24 or 25 weeks to as long as 30 weeks, greatly improving outcomes for the infant.”

Preeclampsia is a hypertensive disorder associated with pregnancy; preeclampsia has no cure or adequate treatment options. Women experiencing preeclampsia suffer from the onset of high blood pressure and excess protein in the urine, called proteinuria, beginning around 20 weeks of pregnancy. In severe cases, red blood cells can break down, blood platelet counts fall, liver and kidney function is impaired and fluid can fill the lungs causing shortness of breath and increasing the risk to both mother and baby. A complication in 2 to 8 percent of all pregnancies, preeclampsia is responsible for 100,000 premature births and more than 10,000 infant deaths in the U.S. every year. The only treatment for the illness is the delivery of the baby and placenta.

Symptoms of preeclampsia arise from a defect found in the placenta associated with abnormally high levels of the protein sFLT1 in the blood, which acts as an on/off switch for inhibiting the growth of new blood vessels. Reducing levels of circulating sFLT1 is considered a promising therapeutic target for the disease.

The study, published in Nature Biotechnology, shows that ‘short interfering RNAs’ or siRNAs can be used to reduce circulating sFLT1 in the blood of pregnant mice. An emerging class of drugs that target nucleic acids, siRNAs degrade the messenger RNAs (mRNAs) that carry the instructions for making proteins from DNA. By reducing the number of mRNAs for a specific DNA sequence, scientists can reduce the number of mature proteins that get made. When siRNAs targeting some of the messenger RNAs that encode sFLT1 were delivered to pregnant mice, scientists were able to reduce the amount of circulating levels of the protein by up to 50 percent.

In collaboration with Annemarie Hennessy, Ph.D., MBA, MBBS, dean of the School of Medicine at Sydney University Medical School, investigators tested this approach in pregnant baboons, an established preclinical model for human preeclampsia. The researchers found that a single injection of siRNA lowers circulating sFLT1 levels and normalizes both high blood pressure and proteinuria in the mothers. “Six years ago, this wouldn’t have been possible,” said Khvorova. “Scientific advances that now allow us to chemically stabilize and produce siRNAs so they can be delivered to tissues outside of the liver have lead to rapid advances in these compounds. The preeclampsia compounds we are developing are an example of what siRNA can do and how far they’ve come.”

Dr. Moore, professor of RNA therapeutics at UMass Medical School, began researching preeclampsia 15 years ago after being diagnosed with the disease and being asked to participate in a study of the illness. “This project is near and dear to my heart,” Moore said. “As exciting as these results are, it still feels like we’re half done. It won’t be complete until we can get a therapy to women. Getting pregnant shouldn’t be one of the most dangerous things a woman can do.”

Although the therapy improves maternal baboon health, the study’s authors also noted a trend toward reduced birth weight in the offspring—indicating that this approach’s effects on neonatal health needs to be studied in greater detail before advancing to clinical trials. The next step for researchers will be to attract funding for the necessary studies needed to further optimize siRNA chemical configuration and extensively test safety, studies necessary before applying for an investigational new drug (IND) application from the U.S. Food and Drug Administration.


Explore further:
Increases in sFLT1 predict the onset of preeclampsia symptoms in mice

More information:
RNAi modulation of placental sFLT 1 for the treatment of preeclampsia, Nature Biotechnology (2018). DOI: 10.1038/nbt.4297 ,

www.nature.com/articles/nbt.4297

Journal reference:
Nature Biotechnology

Provided by:
University of Massachusetts Medical School

About author

Related Articles