Fibrodysplasia ossificans progressive (FOP), commonly known as “stone man disease”, is one of the rarest and most disabling genetic diseases in the world.
Affecting approximately 1 in every 1 million people, FOP causes muscle and connective tissue to gradually turn into bone. This results in formation of a “second skeleton”severely restricting the person’s movement.
The disease is caused by a mutation in the gene ACVR1, which plays a key role in skeletal development during pregnancy and bone repair throughout life. This mutation causes the gene to become overactive, leading to abnormal bone growth in areas where bone should not form.
In most cases, the mutation occurs by chance, without any family history, although it also occurs can be inherited. Just one copy of the mutated gene is enough to cause the disease.
From birth, there are subtle signs of FOP, such as shortened, inward-turned toes. About half of those affected may also have malformed thumbs. Symptoms typically become more evident during childhood and include gradual hardening of the jointsespecially on the neck, back, chest, arms and legs.
Has seizures, or episodes of pain, swelling and stiffnesscan worsen the disease. These outbreaks can occur spontaneously or be triggered by trauma, such as injuries, surgery, or even viral infections, such as the flu. As the disease progresses, additional symptoms may include difficulty eating or speaking if the jaw is affected, hearing loss, and spinal deformities.
By the age of 30, many patients become completely immobile, with their body blocked by extra bone tissue. Life expectancy is significantly reduced, with most patients live to age 56.
Cardiorespiratory failure, caused by the loss of the ability to breathe, is the most common cause of death among patients with FOP, highlights the .
Treatment for FOP is challenging. Pain relievers and anti-inflammatory medications such as corticosteroids can help alleviate symptoms, but surgery to remove excess bone is not an option as it often results in new flare-ups and worsening of the disease.
In 2023, there was a significant advance in the treatment of FOP with the approval of palovarotene, marketed under the brand name Sohonos. The U.S. Food and Drug Administration has authorized its use for women ages 8 and older and men ages 10 and older.
In clinical trials involving 107 patients, those treated with the drug showed a 54% reduction in excessive bone formation compared to those who did not receive the treatment.
