New treatment for a severe vascular disease proves effective

Treatment with thalidomide leads to a striking reduction in symptoms and a subsequent improvement of quality of life in patients with severe arteriovenous malformations. That is the conclusion of a study in 18 patients, performed by Prof. Laurence Boon and Prof. Miikka Vikkula, in a long-standing collaboration between de Duve Institute and the Centre for Vascular Anomalies at University Hospital Saint-Luc.

Arteriovenous malformations (AVMs) are difficult-to-treat vascular anomalies in which abnormal connections are formed between high-pressure blood vessels (arteries) and low-pressure blood vessels (veins). Lesions can arise anywhere in the body. They are painful and may cause recurrent and sometimes life-threatening bleeding, ulceration and functional disability. Though mostly present at birth, AVMs usually become visible and symptomatic in adolescence or adulthood, and often evolve over time with increasingly severe symptoms. Common treatment is embolization (deliberate blocking of blood vessels) followed by surgical resection. However, complete resection is rarely possible and partial resection often leads to dramatic worsening.

Some people with AVMs can live relatively normal lives, but even in less severe cases there is always the risk that the abnormal tangles of blood vessels can burst and may cause a stroke when in the brain. About one in every hundred AVM patients suffers a stroke each year.

“Our group has been studying the causes of vascular abnormalities for 30 years”, says Prof. Vikkula, head of the laboratory of Human Genetics at de Duve Institute. “We have identified several genetic causes and have been able to show that certain mutations activate the signalling inside the cells of blood vessel walls, and this promotes the abnormal formation of blood vessels (angiogenesis). This led us to wonder about the possibility of using thalidomide to inhibit abnormal blood vessel formation”. Thalidomide was used as a sedative drug for pregnant women in the 1950s and it became infamous for its teratogenic properties. These effects were later shown to be due to strong inhibitory effects on angiogenesis of thalidomide.

After showing that a vascular malformation could be corrected in a mouse model, Prof. Laurence Boon from the Centre for Vascular Anomalies at University Hospital Saint-Luc, started in 2010 a clinical study into the use of thalidomide in AVMs. She recruited 18 patients, aged between 19 and 70, with severe malformations that could not be treated by conventional approaches.

“All the patients experienced a rapid reduction of pain, together with cessation of bleeding and the healing of ulcers where these were present”, says Prof. Vikkula. “Three patients with cardiac failure also saw these problems resolved, and one AVM appeared to be completely cured after 19 months of thalidomide and an eight-year follow-up”. The researchers showed in five patients that combined treatment with embolization permitted thalidomide dose reduction with clinical improvement. Reducing the dose led to less side-effects during the treatment.

Further clinical studies are needed to confirm the safety and efficacy of thalidomide treatment in AVMs. “Although our study is relatively small, the results are convincing, and we hope that they will be confirmed by larger trials”, says Prof. Vikkula. These results give great hope for a better future for patients affected by an AVM.

Affected hand of an AVM patient.
(a) Before thalidomide treatment: the AVM recurred despite amputation of the second finger.
(b) Complete healing after 2 years of thalidomide treatment.

(Picture from the article in Nature Cardiovascular Research, see below)

Article describing the research

Case report study of thalidomide therapy in 18 patients with severe arteriovenous malformation.
Boon LM, Dekeuleneer V, Coulie J, Marot L, Bataille A-C, Hammer F, Clapuyt P, Jeanjean A, Dompmartin A & Vikkula M.
Nat Cardiovasc Res (2022) 1: 562–567