Roughly 70 percent of pregnant individuals experience morning sickness, a common condition that involves bouts of nausea or vomiting, or both. It can happen at any time of day and usually subsides after the first trimester. However, for up to 3 percent of pregnant people, morning sickness escalates into a severe and sometimes life-threatening condition called hyperemesis gravidarum (HG). This debilitating condition makes it extremely difficult to keep down food or liquid, leading to severe dehydration and, in some cases, hospitalization. Notable figures like Catherine, Princess of Wales, and comedian Amy Schumer have publicly shared their experiences with HG.
Marlena Fejzo, an assistant professor at the Keck School of Medicine of the University of Southern California, has dedicated her research to understanding the genetics of HG. Having experienced the condition herself during her pregnancies, Fejzo collaborated with 23andMe to identify two genes, GDF15 and IGFBP7, associated with HG. Her groundbreaking research, published in a 2023 study in Nature, confirmed the role of the hormone GDF15 in triggering severe morning sickness in individuals with HG. Fejzo’s work sheds light on the underlying mechanisms of this debilitating condition and opens the door to potential treatments.
Currently, Fejzo is focused on investigating treatments for HG, including exploring the use of the diabetes drug metformin and developing more targeted antibody therapies. Her dedication to advancing the understanding and treatment of HG has earned her recognition, including the BioInnovation Institute & Science Translational Medicine Prize for Innovations in Women’s Health.
In a recent interview with Scientific American, Fejzo discussed the challenges of hyperemesis gravidarum, the discovery of GDF15, and the progress towards finding effective treatments for this condition. She emphasized the need for more research and awareness surrounding HG, a condition that affects many pregnant individuals worldwide.
Fejzo’s personal experience with HG has fueled her passion for unraveling the mysteries of this condition. Through her research, she aims to provide hope and relief for those suffering from hyperemesis gravidarum and pave the way for improved treatments in the future. Genetic research has been making significant strides in understanding the underlying mechanisms behind hyperemesis gravidarum (HG), a severe form of nausea and vomiting during pregnancy. One researcher, who was fortunate to receive a kit from 23andMe for her brother, embarked on a journey that led to groundbreaking discoveries in the field.
Initially, the researcher collaborated with 23andMe to add hyperemesis-related questions to their surveys, which ultimately resulted in the publication of a paper demonstrating a strong link between hyperemesis and the nausea and vomiting hormone GDF15. This discovery paved the way for further investigations, including sequencing study participants by the pharmaceutical company Regeneron.
In a cohort of participants with a mutation in GDF15, the researcher found that the mutation significantly increased the risk of hyperemesis. However, a surprising finding emerged when examining the children of these women with the mutation – those who inherited the gene were actually less likely to experience hyperemesis. This led to the hypothesis that the presence of the mutation in the baby played a role in whether or not the mother would develop hyperemesis.
Collaborating with an endocrinologist at the University of Cambridge, the researcher delved deeper into the genetic variants associated with GDF15 production. Contrary to expectations, these variants were linked to lower levels of the hormone, suggesting a potential desensitization mechanism that could be protective against hyperemesis. This finding was supported by evidence from both animal models and human studies, highlighting the complex interplay between genetics and pregnancy-related symptoms.
The evolutionary perspective on the role of GDF15 in pregnancy shed light on why this hormone may have evolved as a mechanism to protect against potential dangers during sensitive states such as pregnancy. Studies have shown that the absence of morning sickness symptoms may indicate a higher risk of miscarriage, emphasizing the importance of GDF15 production in ensuring the healthy progression of pregnancy.
In terms of treatment options for HG, the researcher has explored the potential benefits of the diabetes drug metformin, which has been shown to increase GDF15 levels. Preliminary findings suggest a positive association between metformin use prior to pregnancy and a reduced risk of hyperemesis, offering hope for improved management strategies in the future.
Overall, the research journey of this dedicated scientist has illuminated key insights into the genetic and physiological factors influencing hyperemesis gravidarum, opening up new avenues for understanding and potentially treating this challenging condition. Metformin, a commonly prescribed medication for diabetes, is now available in generic form, making it more accessible to a wider population. This equitable approach allows more patients to benefit from the medication without the high cost associated with brand-name drugs.
Recently, a prospective study of metformin was initiated in patients to determine its effectiveness in treating various conditions. While the results of this study are still pending, there is promising news from NGM Biopharmaceuticals. The company has treated its first patient with a drug that targets the receptor for GDF15, a hormone associated with various health issues. A clinical trial has also been initiated to further explore this treatment approach.
The potential success of these new treatment options is on the horizon, and researchers are hopeful that they will provide effective solutions for patients in need. This exciting time in the field of medicine marks a significant step forward in the development of innovative therapies.
Editor’s Note: It is important to mention that individuals with hyperemesis gravidarum have a specific version of the GDF15 gene that affects the production of the GDF15 hormone. This information sheds light on the complex nature of genetic factors in health conditions and underscores the importance of personalized medicine approaches.
In conclusion, the advancements in medical research and the development of new treatment options offer hope for patients facing various health challenges. By staying informed and exploring innovative therapies, we can pave the way for a healthier future for all.
