Aurora magazine

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.

Source: medicalxpress.com

Hereditary hemorrhagic telangiectasia or HHT, from the English abbreviation, is an inherited genetic disease. It affects about 1 in 10,000 individuals and affects mainly blood vessels. Unfortunately the diagnosis is often difficult, due to the variety of symptoms.

The disease affects only a small part of the blood vessels, but with devastating consequences. Defective arteries enter the venous circuit directly, without capillaries acting as intermediaries. The pressure of the arterial blood is therefore excessive for the vein walls, which are gradually damaged. In the long run they break, causing a hemorrhage that can affect tissues or mucous membranes.

Hereditary hemorrhagic telangiectasia mainly affects skin, mucous membranes of the nose and mouth, stomach, intestine, liver, lungs and brain. Depending on the veins affected, the disease can manifest itself in different ways. The most obvious symptom is bleeding, but bleeding is not always visible from the outside. In some cases, the veins form fistulas that rarely bleed and are therefore more difficult to detect.

Each patient has different symptoms, which makes the diagnosis difficult. We are working on a genetic test, but today the diagnosis is mainly based on clinical observations. The criteria used are:

• Recurrent nose blood;
• Dilation of blood vessels on the lips, in the oral cavity and in the nose;
• Fistulas in internal organs;
• Familiarity.

For the moment it is not possible to avoid vascular lesions, so there is no definitive therapy. However, it is possible to cure most vascular lesions. As for epistaxis, they are largely avoidable with a good humidification of the domestic environment.

Source: hht.it

Researchers at Massachusetts General Hospital in Boston have isolated the anti-Alzheimer gene from the DNA of a Colombian woman. The mutation is called APOE3ch and contrasts the genetic predisposition to the disease, very common in Colombia. Thanks to this variant, the woman lived for over 30 years without showing any symptoms, despite the other variants.

In Colombia there are about 6,000 people with the E280A mutation, which increases the risk of getting Alzheimer's. The variant is also linked to an early form of the disease, which begins as early as 40 years. Yet the woman became ill only in old age. The researchers then searched for the causes of this phenomenon. Accumulations of beta-amyloid had formed in the woman's brain, which should have made her sick.

Nevertheless, his brain has resisted damage for decades. The merit was the APOE3ch mutation, which protected the neurons from the plaques that were supposed to destroy them. The variant has in fact prevented the formation of toxic neurofibrillary clusters, which are determinant in Alzheimer's disease. The discovery sheds new light on Alzheimer's research.

According to the authors of the study, the disease could be fought not by avoiding its appearance but by making the brain more resistant. Just like it happened to the woman in question. However, further studies will be needed to understand if it is really possible to apply this principle to the pharmacological field.

Source: repubblica.it

Researchers from the University of Manchester have discovered the possible cause of a serious genetic disease. It is actually a group of diseases that affect the nervous system, causing paraplegia and epilepsy. It is called hereditary spastic paraplegia and at the moment there is no cure. Thanks to the discoveries made, however, it will be easier to develop treatments.

The diseases that fall under the umbrella of hereditary spastic paraplegia were already known, at least in part. Over the years, researchers have identified several common genetic variants among patients. None of these, however, seemed to be the real cause of the disease, which therefore remained unknown.

A team of researchers from Manchester and Amsterdam worked to identify the real cause of hereditary spastic paraplegia. Thanks to studies on zebrafish and patient samples, they detected an anomaly in the PCYT2 gene. This could be the variant that determines the appearance and severity of the disease. Zebra fish with normal or slightly reduced PCYT2 activity had a good survival rate. In contrast, those with PCYT2 absent or inactive lived little.

The gene encodes an enzyme that produces the lipids that make up cellular membranes, especially those of neurons. When it is missing, the cells deteriorate more quickly and the symptoms described above occur.

Source: medicalxpress.com