Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease that prevents the formation of blood vessels. This leads to the appearance of sometimes lethal complications. Scientists at the Feinstein Institute for Medical Research may have revealed the molecular mechanisms of the disease. This allowed them to develop two possible drugs that could treat the most devastating complications. For the time being, tests have been limited to animal models.
The disease is characterized by the development of cells in blood vessels and hemorrhagic lesions. In the long run, it damages internal organs and reduces their functionality. It is known to be caused by the ALK1 gene, but the mechanism is still unclear. Dr. Marambaud and his colleagues started from these premises and developed a possible treatment. This is based on drugs already used for other diseases, which could inhibit the complications of hereditary haemorrhagic telangiectasia.
The researchers found that the mTOR and VEGFR2 pathways were ultra-activated in sick animal models. This was also evident in human patients. The drugs being studied interact with these, thus acting on part of the symptoms of the disease. They are in fact sirolisum and nintedanib, inhibitors of the two identified pathways. The first is used to open obstructed arteries and reduce the risk of rejection in transplants. The second is a drug used for the treatment of idiopathic pulmonary fibrosis.
Used together, the two drugs reduce most of the more serious symptoms of the disease. This at least in animal models: further studies will be needed to prove its efficacy in humans.