Breaking News
April 25, 2019 - Association Insurance Pushes On Despite Court Ruling
April 25, 2019 - Traditional and e-cigarette users may be more receptive to smoking cessation interventions
April 25, 2019 - Delving into tumor’s cellular lineage may offer clues for customized therapies
April 25, 2019 - Two studies uncover brain mechanisms underlying decision making process
April 25, 2019 - Cardiometabolic Risk Better ID’d in Children Reclassified to Higher BP
April 25, 2019 - How the obesity epidemic is taking a toll on our bones and joints
April 25, 2019 - E-cigarettes contaminated with dangerous microbial toxins
April 25, 2019 - Researchers document specific characteristics of storefront tobacco advertisements
April 25, 2019 - Oncotype DX-guided treatment could reduce cost for breast cancer care, study suggests
April 25, 2019 - New review highlights how lifestyle affects our genes
April 25, 2019 - Study provides evidence that blood tests can detect Alzheimer’s risk
April 25, 2019 - Computer program mimics natural speech using brain signals from epilepsy patients
April 25, 2019 - Physicians turning to antibiotic alternatives for long-term acne treatment
April 25, 2019 - Preschool Is Prime Time to Teach Healthy Lifestyle Habits
April 25, 2019 - Study finds insidious and persistent discrimination among physician mothers
April 25, 2019 - Newly identified skin-gut communication helps illuminate link between food allergy and eczema
April 25, 2019 - Thiazide use linked with reduced risk of low energy fractures in people with Alzheimer’s
April 25, 2019 - Some women are biologically more resilient than others to PTSD
April 25, 2019 - The Current issue of “The view from here” is concerned with Partnerships and Alliances
April 25, 2019 - Imaging method reveals long-lived patterns in cells of the eye
April 25, 2019 - Podcast: KHN’s ‘What The Health?’ The Abortion Wars Rage On
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 - Researchers use brain scans to provide better understanding of unconscious bias
April 24, 2019 - Blocking BRAF ubiquitination may be an effective treatment approach in melanoma
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
Stanford researchers find that small molecule may help treat enzyme deficiency

Stanford researchers find that small molecule may help treat enzyme deficiency

image_pdfDownload PDFimage_print

Scientists are one step closer to developing a treatment for a genetic enzyme deficiency that can cause red blood cells to break down in response to infections or certain drugs or foods, like fava beans. In extreme cases, reactions can be fatal.

The research, led by Stanford’s Daria Mochly-Rosen, PhD, and Sunhee Hwang, PhD, identified a small molecule that can patch up the defective enzyme. The goal is to convert this molecule into a safe daily treatment for people with the enzyme deficiency.

The research appears in Nature Communications.

When it functions properly, the enzyme, called glucose-6-phosphate dehydrogenase or G6PD, protects red blood cells from oxidative stress, which occurs when unstable atoms called free radicals steal electrons from red blood cells’ protective membrane, causing them to break down.

However more than 400 million individuals worldwide are born with mutated G6PDs, leaving their cells more susceptible to oxidative stress and deterioration. When exposed to specific foods, medications, infections or environmental factors, patients can experience hemolytic anemia, where their red blood cells are destroyed faster than the body can produce them. This results in symptoms such as abdominal pain, increased heart rate, shortness of breath, fever, jaundice and brain damage in severe cases or if left untreated.

Many of the people with the G6PD mutation live where malaria is common. Unfortunately, chloroquine, a commonly used antimalarial drug in low and middle income countries, is known to trigger hemolytic anemia in G6PD-deficient patients. Due to limited resources, malaria patients in these regions are rarely tested for G6PD deficiency before taking chloroquine. This puts individuals with the disorder in a dangerous predicament.

Mochly-Rosen and Hwang don’t believe that patients should have to choose between malaria or a hemolytic episode.

They thought the molecule they had found, known as activator of G6PD-1 (abbreviated as AG1), might provide some protection from the condition. To see, the researchers and collaborator Karen Mruk, PhD, exposed zebrafish embryos to chloroquine, causing blood to pool in the veins and physical changes in the embryo’s structure. Incredibly, when they treated the embryos with AG1, they noticed a decrease in both oxidative stress and the physical defects. Long term, the goal is to give a drug similar to AG1 together with chloroquine for people with G6PD deficiency who are exposed to malaria.

However, moving from fish to humans is a tricky business.

Along with correcting G6PD-deficiency, AG1 has an additional purpose. By testing AG1 on human blood samples, the team found that the molecule helps prolong red blood cells’ 42-day shelf-life by reducing the rate of hemolysis. This could be a huge help in lengthening the amount of available time between blood donation and transfusion.

But, “even though we have some promising data, this molecule is quite a mild activator,” Hwang said. “We want to increase the mutant G6PD enzyme activity to 60 percent of the normal enzyme, which is known to be sufficient in humans. As of now, we have only activated it by 20 or 30 percent.”

Currently, Andrew Raub, a graduate student who is working in the Mochly-Rosen lab, is trying to make a new form of AG1 that can be used in human trials. By examining the crystal structure of AG1, the team can understand where the molecule binds and create a more stable and effective drug.

And the new molecule could help with more than just red blood cells, Mochly-Rosen believes.

“It is assumed that the deficiency in this enzyme is only important for maintaining the integrity of red blood cells,” Mochly-Rosen said. “But I’m quite confident that this is really an underestimation of the contribution of this mutation to human health.”

For Mochly-Rosen, this study also holds personal significance. In addition to activator of G6PD, the acronym AG stands for the initials of the University of California, San Francisco professor and neuroscientist Adrienne Gordon, a close friend and mentor of Mochly-Rosen who died in 2015. “She was my mentor since graduate school, I was always bouncing ideas against her, and she love this G6PD project. And so, we named the molecule AG for her as well.”

Photo of Sunhee Hwang, at left, and Daria Mochly-Rosen by Helen Santoro

Tagged with:

About author

Related Articles