$1.7 million NIH grant to fund research on rare genetic bleeding disorder
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The NIH has awarded a $1.7 million grant to fund research into potential treatments for hereditary hemorrhagic telangiectasia, a frequently misdiagnosed but potentially life-threatening bleeding disorder.
The agency awarded the 4-year grant to Philippe Marambaud, PhD, a professor at the Institute of Molecular Medicine at Feinstein Institutes for Medical Research.
Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a condition in which blood vessels form improperly. This can result in bleeding in major organs, including the brain.
No treatments exist for HHT; however, some interventions can help to control bleeding.
“The first manifestation of HHT is usually nosebleeds, which are manageable at the beginning but become more and more problematic and may even lead to anemia,” Marambaud said in an interview with Healio. “These patients cannot live normally; they are affected in their daily living and work activities. Cauterization can be done for the nosebleeds, but in the long term it’s not easy to manage. There is a need to find more effective treatments, and this is what our research is looking at now.”
Marambaud discussed the debilitating nature of HHT, the challenges in diagnosing it and potential treatments that his lab will investigate.
Question: What is HHT?
Answer: HHT is a genetic disease, a bleeding disorder that leads to lesions in the blood vessels in different parts of the body. HHT is relatively rare, affecting about one in 5,000 individuals, but extremely debilitating. Obviously, because it is genetic, it can affect many members of the same family. This can be a huge concern when several members of a family are affected.
Q: Why is HHT misdiagnosed so frequently?
A: Actually, it’s easy to diagnose HHT now; a genetic test is available. However, because it is a rare disease, the primary care physician might not think about HHT right away, because nosebleeds happen to a lot of people. Family history is helping the PCP direct these patients to a specialist, at which time they will be genetically tested. So, it’s getting better, but still very often misdiagnosed.
Q: How is HHT currently managed and what will your research evaluate?
A: A lot of interventions can be done by an ear, nose and throat specialist, if nosebleeds are the main problem. If the lesions are in the lungs or the brain, embolization can be performed, but this is an invasive procedure. Blood transfusions alleviate anemia, but there is no cure. It’s very difficult for patients to cope with the different problems once they accumulate.
Our research is trying to better understand the mechanisms that are defective in the lesions that develop. The lesions are formed by the accumulation of specific endothelial cells, which are important for the formation of the blood vessel walls. We found two markers, endothelial mTOR and VEGF receptor 2, for which drugs already are available. Our goal is to see whether, by using these drugs, we can intervene preclinically in a mouse model. We will use an in vitro system in the lab to test the hypothesis that these drugs can be beneficial to patients.
We are not doing clinical trials in my lab, but we collaborate with HHT centers. Once the project has delivered sufficient evidence that these two markers are important for the disease process, based on the in vitro mechanisms that we study, the hope is that clinical trials can be initiated in other institutions. Working with already approved drugs has a tremendous advantaged because it could fast track the testing of the therapeutic value of this program.
Q: Are any other drugs being developed for HHT?
A: There are a lot of off-label prescription attempts. Some people are trying drugs that might change the way blood vessels heal, such as antiangiogenic drugs. Some promising clinical trials are emerging, but more basic research is required. Very often, case reports or studies are based on observations we make by accident, because the patient was treated for another reason and showed some improvement. We are still at the very beginning in our question for a cure.
For more information:
Philippe Marambaud, PhD, can be reached at 350 Community Drive, Manhasset, NY, 11030.
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