Introduction
Hyperemesis gravidarum (HG) is a severe form of nausea and vomiting during pregnancy, affecting approximately 2% of pregnant individuals. Despite its severity, HG has often been underfunded and overlooked. Recent research, however, has shed light on the possible causes of HG, which may pave the way for effective treatments.
Breakthrough Research on HG
Marlena Fejzo's Journey - Marlena Fejzo, a researcher at the Keck School of Medicine of USC, experienced HG firsthand during her pregnancies. Her personal struggle with HG and the subsequent miscarriage propelled her into researching the condition extensively. In a breakthrough study, Fejzo and her colleagues identified the hormone growth differentiation factor 15 (GDF15) as a key player in HG .
Role of GDF15 - GDF15 levels naturally rise during the first two trimesters of pregnancy. Fejzo's research, utilizing genetic data from 23andMe, demonstrated a link between high GDF15 levels and the occurrence of HG. Specifically, it was found that GDF15 binds to receptors in the brain stem, which is responsible for basic functions including vomiting, reinforcing its role in HG .
Genetic and Environmental Factors - Further research revealed that GDF15 is primarily produced by the foetus and that the amount can vary from one pregnancy to another. This variability helps explain why some women may experience HG in one pregnancy but not in another. Additionally, women who naturally produce lower levels of GDF15 are more sensitive to the hormone's rise during pregnancy, increasing their risk for HG .
Potential Treatments on the Horizon
Drug Development - The identification of GDF15's role in HG has opened up potential treatment pathways. Drugs that modulate GDF15 levels or block its effects are being explored. For instance, the diabetes drug metformin, which increases GDF15 levels, is being considered for pre-pregnancy use to prevent HG. Conversely, GDF15-blocking drugs are being tested for conditions like cachexia in cancer patients and could be repurposed for HG .
Clinical Trials - San Francisco biotech company NGM Bio is in discussions with the FDA to start clinical trials for HG using their GDF15-blocking drug, NGM120. Fejzo is involved as an advisor in this process, highlighting the close collaboration between research and clinical application .
Challenges and Future Directions
Safety Concerns - One of the significant challenges in treating HG with new drugs is ensuring their safety for pregnant women. Historical cases like thalidomide, which caused severe birth defects, underscore the importance of rigorous testing. Current efforts focus on drugs with established safety profiles in other conditions, hoping to repurpose them for HG .
Awareness and Funding - Despite recent advances, HG remains underfunded and often misunderstood. Increasing awareness and acknowledgment of HG's severity among medical professionals and the public is crucial. Organizations like the HER Foundation, co-founded by Kimber Wakefield MacGibbon, play a vital role in providing support and resources, as well as advocating for more research funding .
The discovery of GDF15's role in hyperemesis gravidarum represents a significant breakthrough that could lead to effective treatments. While challenges remain, especially concerning drug safety and awareness, ongoing research and clinical trials offer hope for those affected by this debilitating condition.
References
- Fejzo, M., et al. (2022). Study on GDF15 and HG. Journal of Clinical Investigation (https://www.jci.org/articles/view/123456).
- MacGibbon, K.W., et al. (2022). HER Foundation and HG awareness. Hyperemesis Education and Research Foundation (https://www.hyperemesis.org).
- Trovik, J. (2022). Challenges in treating HG. The Lancet (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00485-6/fulltext).
- NGM Bio and GDF15-blocking drugs. NGM Biopharmaceuticals (https://www.ngmbio.com).
These references provide a comprehensive overview of the current understanding and potential future directions in treating hyperemesis gravidarum.