New Potential Solution to Rare Genetic Bleeding Disorder HHT Discovered
Mon, October 25, 2021

New Potential Solution to Rare Genetic Bleeding Disorder HHT Discovered

Hereditary Hemorrhagic Telangiectasia interrupts the normal function of the blood vessels.  / Photo by: tussik13 via 123rf


Patients diagnosed with hereditary hemorrhagic telangiectasia (HHT) experience nosebleeds, sometimes daily and often starting in childhood, headaches, shortness of breath, suffering from persistent iron deficiency anemia, and chronic stomach hemorrhaging.HHT a rare genetic bleeding disorder that is potentially life-threatening. 

Understanding Hereditary Hemorrhagic Telangiectasia

HHT is a genetic disorder that is inherited from parents. Being an autosomal dominant disorder, one of the parents of a patient must have HHT. Someone who has HHT also has a 50 percent chance of passing the condition to his or her children. The disorder causes abnormal connections, which is referred to as arteriovenous malformations (AVMs) in the veins and arteries. It interrupts the normal function of the blood vessels. 

The vascular obstructions, AVMs, are like Gordian knots in a way that they block the normal blood flow in the body, depriving tissues of proper oxygen. An ambitious study conducted by scientists from the Feinstein Institute for Medical Research in New York allowed them to determine the molecular mechanisms that drive the condition. This enabled them to also create two of the shelf medications proposed as the solution to HHT as they can reverse or block some of the devastating complications brought by the disorder.

While their study was only tested in animals, the scientists explained that anemia, retinal bleeding, and retinal AVMs were prevented in their test subjects. In other test animals, their gastrointestinal bleeding was also reduced. Medical research platform Medical Xpress stated that the team’s discovery will serve as the groundwork for clinical trials on human participants.

Major HHT Symptoms Reduction or Reversal

Lead scientist Dr. Philippe Marambaud said that HHT is a genetic disorder. Its main manifestations are nosebleeds (epistaxis), anemia, and internal bleedings. He details how one of the mutated genes from either the father or the mother would already be sufficient to cause the disease to the child. Dr. Marambaud’s institute located in Long Island has already gained an international reputation for studying innovative treatments and solving complex diseases and medical conditions.

Prevalence of HHT Worldwide

Dr. Marambaud and the team’s study highlights that there are about 1.4 million people worldwide affected by such a rare bleeding disorder. Furthermore, about 85 percent of the patients diagnosed with HHT carry the gene mutations in one of two genes, either endoglin or ALK1.

Repurposing the Two Medications to Help HHT Patients

The Feinstein Institute scientists said that the two off the shelf medications they are referring to are available in the US and were given a green light by the United States Food and Drug Administration for its capability to reduce or reverse the disease-related pathology. These drugs are sirolimus and nintedanib. The sirolimus drug is a macrolide compound used to coat coronary stents and prevent organ transplant rejection because of its immunosuppressant functions. It is also being used to treat rare lung disease. 

The nintedanib, on the other hand, is an oral medication for the treatment of non-small-cell lung cancer and idiopathic pulmonary fibrosis. The medication is likewise conventionally used to treat a disease that is marked by scarring and stiffening of the lung tissue, impairing a person’s ability to breathe.

The team suggests that repurposing the two drugs may offer therapeutic benefits for patients diagnosed with HHT. In animal bodies, the synergistic effect of the two off the shelf drugs show a potential promise to treat HHT. The group also said that doctors currently don’t have treatments to control the myriad of symptoms of HHT patients. They only suggest interventions, but these are not cures for the condition.

They suggest that patients should seek the help of physicians who specialize in rare hereditary disorders. Dr. Marambaud clarifies that calling the drug combination as a potential “cure” may already be an ambitious claim. Instead, clinical trials on human subjects should first be done to determine the drugs’ therapeutic potential not just in animal bodies.

The team’s study titled "Correcting Smad1/5/8, mTOR, and VEGFR2 treats pathology in hereditary hemorrhagic telangiectasia models" has also appeared in The Journal of Clinical Investigation.


The nintedanib is an oral medication for the treatment of non-small-cell lung cancer and idiopathic pulmonary fibrosis. / Photo by: Vladimir Soldatov via 123rf


Hereditary Hemorrhagic Telangiectasia: Statistics

In other data provided by the US National Library of Medicine, it was stated that HHT is believed to affect between 1 in 5,000 and 1 in 10,000 people worldwide. The severity of symptoms also varies, such as the frequency of nosebleeds. The causes are mutations in the genes, including the SMAD4, ENG, and ACVRL1. Type of HHT is caused by mutations in the ENG gene. 

Type 2 HHT is caused by gene mutations in the ACVRl1. Lastly, hereditary hemorrhagic telangiectasia syndrome or juvenile polyposis is caused by the gene mutations in SMAD4. All genes mentioned have instructions on how to make proteins found in the blood vessels’ lining. Then, the proteins interact with various growth factors that also control the development of the blood vessels of the person. The Type 3 hereditary hemorrhagic telangiectasia may be linked with a higher risk of involvement of the liver.