Despite the positive results from a case study of thalidomide therapy in patients with severe arteriovenous malformations, researchers have found an increase in symptoms and quality of life for patients treated with thalidomide.
Miikka Vikkula, a PhD, professor, and the de Duve Institute, presented the findings in Nature Cardiovascular Research, which stated that thalidomide should be used in these patients, but it was beneficial to have clinical confirmation that we were correct. This study, according to Alexandre Reymond, highlights the need for effective molecular therapies for severe arteriovenous infections.
AVMs are abnormal ties between blood vessels and veins that alter normal blood flow. vascular abnormalities are common in the body, which includes abnormal connections between high-pressure arteries and low-pressure veins that are beneficial to the normal functioning functioning, according to the researchers. AVMs are extremely painful and may result in swelling, local tissue ischemia, as well as cardiac overload.
AVMs are usually found in adolescents or adulthood as the person grows. Some severe cases are usually performed with surgery or embolization (the injection of an agent that destroys the blood vessels locally, thus inducing scarred tissue), although this is rarely completely effective and can result in severe complications. Complications of therapy such as cutaneous necrosis, peripheral nerve injuries, and even death can cause an AVM.
Some people with AVMs can maintain normal lives, but there is always the risk that abnormal tangles of blood vessels might burst and cause a stroke when in the brain. A huge need for novel therapies is awaiting attention.
Thalidomide, which was initially found to be a form of sedative therapy for pregnant women in the 1950s, has become known for its teratogenic properties (phocomelia), which was later shown to be due to inhibitory effects on angiogenesis. Thalidomide, however, was also shown to be beneficial for the treatment of cerebral AVM in a mouse model.
Vikkula reports that our group has studied the causes of vascular abnormalities for 30 years. We have identified several genetic problems and have been able to demonstrate that certain mutations activate the signaling inside the blood vessel wall cells, thus promoting abnormal blood vessel formation (angiogenesis). This led us to wonder about the possibility of using thalidomide to inhibit abnormal blood vessel formation.
Laurence Boon, PhD, from the Centre for Vascular Anomalies at Saint Luc University Hospital in Brussels, studied 18 patients with AVMs as a potential treatment for their condition. Participants were aged 1970 years, had severe malformations that could not be treated by conventional methods, and all agreed to use contraception for at least four weeks before starting thalidomide.
After two months and 52 months, participants received 50 mg, 100 mg, or 200 mg of thalidomide per day. Thalidomide was rapidly effective in alleviating chronic pain, and decreased bleeding in large stage III and stage IV AVMs for which conventional therapies had failed.
Vikkula stated that all patients were treated with rapid pain, as well as for removing bleeding and removing ulcers where these were present. Three patients with cardiac failure also saw their problems resolved, and one AVM appeared to be completely cured following 19 months of thalidomide and an eight-year follow-up.
The investigators continued, with eight AVMs at an end of the thalidomide treatment lasting 58 months, four recurred after a normal duration of 11.5 months. In three patients (patients 4, 5, and 12), the AVM decreased in size and vascularization on arteriography.
In five patients, combining therapy with embolization reduced the dosage of thalidomide to 50 mg per day. According to Vikkula, because a higher dosage was associated with side effects, particularly fatigue and peripheral neuropathy, and damage to the nerves outside the brain and spinal cord, which causes weakness and numbness. However, after thalidomide was removed, the researchers concluded.
The results suggest that thalidomide is effective in the management of extensive AVMs that are refractory to conventional therapy. Further research is needed to establish the safety and efficacy of the thalidomide treatment in AVM.
We know that thalidomide is driven by the vascular endothelial growth factor (VEGF), a signaling protein that stimulates the growth of new blood vessels. VEGF levels are high in vascular abnormalities such as AVMs, and it is therefore probable that thalidomide reduces signaling via the angiogenesis-promoting pathways. Although our research is only small, the findings are surprising, and they will be confirmed by larger trials.
One further advantage of the use of thalidomide in the treatment of AVMs would be the cost. Two other medicines, recently developed for oncology and being tested for treating AVMs, cost up to twelve times as much, as are capable of causing several side effects.