ENPP1 Deficiency is a rare genetic disease linked to disruptions in the PPi-Adenosine Pathway, leading to severe, lifelong cardiovascular and musculoskeletal issues.
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ENPP1 Deficiency
People with ENPP1 Deficiency have one or two ENPP1 gene mutations, which may cause ENPP1 enzyme activity to be reduced or even absent. ENPP1 is important in regulating the levels of two key molecules: PPi and adenosine. In ENPP1 Deficiency, the body has trouble with bone formation due to low levels of PPi and maintaining blood vessel health due to low levels of PPi and adenosine.
There are currently no approved therapies for ENPP1 Deficiency.
ENPP1 Deficiency affects people in different ways and can affect people of all ages. The disease may vary in terms of severity of signs and symptoms – even among people in the same family. New symptoms can appear at any age and tend to progress over an individual’s lifetime.
People who have two variants in the ENPP1 gene (biallelic ENPP1 Deficiency) can suffer from a host of complications shortly after birth, in their childhood, and through adulthood. Learn more about the three forms of the disorder:
This rare and serious condition affects babies before and shortly after birth. In GACI, hydroxyapatite crystals build up in the walls of the arteries. This buildup stiffens and narrows arteries, which makes it hard for blood to flow properly. As a result, babies with GACI may have serious medical problems because their heart and other organs cannot get enough oxygen-rich blood. GACI can cause symptoms like heart failure, high blood pressure, breathing difficulties, or failure to thrive. Infants with GACI have a poor prognosis, with approximately 50% mortality before the age of 6 months despite supportive care.
Children with ARHR2 caused by ENPP1 Deficiency develop bone issues due to low levels of phosphate in their blood (hypophosphatemia). These children often experience symptoms such as weak bones, bowed legs, and impaired growth. Children with ARHR2 may also develop hearing loss. Notably, not all children with ARHR2 have a medical history of GACI, but those who do may continue to have high blood pressure throughout childhood.
Osteomalacia is a softening of the bones. In people with ENPP1 Deficiency, bone softening can continue and progress throughout adulthood. Osteomalacia can cause fractures or significant pain that impairs quality of life. In addition, adults may have painful or immobile joints and ligaments due to calcifications around the knees, hips, ankles, hands, and neck.
Additionally, some infants presenting with symptoms of GACI – including vascular calcification and cardiovascular complications – may only have one variant in the ENPP1 gene.
INZ-701 is an ENPP1 enzyme replacement therapy (ERT) given as an injection under the skin (called a subcutaneous injection) that is designed to increase PPi and adenosine in the body to help improve or prevent symptoms of ENPP1 Deficiency.
INZ-701 is an investigational product and that has not yet been approved by the U.S. Food and Drug Administration or any other health regulatory authority.
We are enrolling infants and children with ENPP1 Deficiency in clinical trials for a potential new treatment. Your child’s participation can help us better understand this disease, evaluate the safety and efficacy of INZ-701, and inform future treatment options.
