Vienna, Austria – New research shows that the infamous drug thalidomide may finally find a useful purpose, which is to prevent bleeding and strokes.
Although the drug has had a bad history of causing birth defects for decades, researchers say patients with diseased blood vessels have benefited from using the drug. All 18 volunteers experienced a significant reduction in symptoms and improvements in quality of life – with one of them making a full recovery.
A repurposed drug could revolutionize the treatment of arteriovenous malformations (AVMs), which affect more than three million people worldwide. The genetic disorder causes swelling and disfigurement, and it usually worsens over time.
“All patients experienced a rapid reduction in pain, along with a cessation of bleeding and healing of ulcers if present,” lead author Professor Mika Fikula of the Catholic University of Louvain says in an information release. “The three patients with heart failure also saw their problems resolved, and one of them appeared to be completely cured after 19 months of thalidomide and eight years of follow-up.”
“We know that thalidomide acts through vascular endothelial growth factor (VEGF), a protein that signals the growth of new blood vessels,” Vikola adds.
“VEGF levels are high in vascular abnormalities such as AVMs and thus thalidomide likely reduces signaling via pathways promoting angiogenesis. Although our study is only small, the results are convincing, and we hope to be confirmed by larger trials.”
Thalidomide has a dark past
Thalidomide is one of the most controversial drugs of all. In the late 1950s and early 1960s, doctors gave it to pregnant women to combat morning sickness. However, their children were born without limbs. Scientists later discovered that the drug inhibits the growth of blood vessels in the womb, which led to the drug being banned worldwide.
These same properties, known as antiangiogenic, are now attracting interest in other areas. Two other drugs recently developed for use against cancer are being tested to treat AVMs at up to 12 times the cost. It also has many side effects.
“We assumed that thalidomide should work in these patients, so our results weren’t a surprise, but it was great to get clinical confirmation that we were right,” says Professor Fikola. “In our view, this is a progressive discovery and provides a solid foundation for the development of molecular therapies for antivehicle diseases.”
The researchers presented the results of the annual conference of clinical trials of the European Society of Human Genetics in Vienna.
“Our group has been studying the causes of vascular malformations for 30 years,” the researcher continues. “We have identified several genetic causes and have been able to show that some mutations activate signals within the cells of the blood vessel wall and this promotes abnormal formation of blood vessels (angiogenesis). This led us to question the possibility of using thalidomide to prevent abnormal angiogenesis.”
Does thalidomide cause any other side effects?
The volunteers, aged between 19 and 70, had severe abnormalities that could not be treated with conventional methods. They had to agree to use contraception for at least four weeks before starting thalidomide and continuing for four weeks after stopping treatment. Because thalidomide is present in semen, men also had to agree to use condoms during sex.
Patients received a dose of 50, 100, or 200 mg daily for between 2 and 52 months. Eight cases stabilized after stopping treatment, for an average of four and a half years. Combined therapy with embolization, in which arteries or veins within an arteriovenous malformation are blocked by an agent that destroys vascular wall cells, allowed the dose of thalidomide to be reduced to 50 mg daily in five patients.
Reducing the dose as much as possible was important because taking a larger dose resulted in side effects, particularly fatigue, damage to nerves near the brain and spinal cord, and weakness and numbness in the hands and feet.
“This study demonstrates not only the health and economic benefits of drug reuse – even the worst – but also how genetic research can lead to real breakthroughs in treatments for challenging and troublesome conditions,” says Professor Alexandre Raymond, Conference Chair.
Arteriovenous tangles are abnormal tangles of vessels that connect arteries and veins that alter normal blood flow. It is very painful and causes bleeding and disfigurement in the affected part of the body as well as heart problems.
It is usually congenital, and is often only noticed during adolescence or adulthood as the person grows. Severe cases are usually treated with surgery or embolization. However, these deformed blood vessels can burst. About one in 100 patients suffers a stroke each year. Doctors now use thalidomide to treat leprosy and other skin diseases, as well as some types of cancer.
The results have also been published in Cardiovascular Nature Research.
Writer Mark Waghorn, columnist for the Southwest News Service, contributed to this report.