A Race Against Time: Treating ENPP1 Deficiency, with Douglas A. Treco, Ph.D.

In an interview with The Educated Patient, Douglas A. Treco, Ph.D., CEO and chairman of Inozyme Pharma, discusses the role of ENPP1, an enzyme crucial for regulating calcium and pyrophosphate (PPi) balance in the body. ENPP1 deficiency leads to severe diseases, primarily generalized arterial calcification of infancy (GACI) in newborns and autosomal recessive hypophosphatemic rickets (ARHR2) in older children. These conditions cause life-threatening cardiovascular complications, abnormal bone development, progressive mobility issues and hearing loss.

ENPP1 generates two key molecules: PPi and adenosine, which prevent abnormal calcification and vascular blockages. Without these molecules, calcium and phosphate accumulate in soft tissues and blood vessels, leading to hardened arteries and restricting normal function, particularly in the heart. Babies with GACI often develop severe heart failure due to calcified coronary arteries, with nearly half not surviving beyond 6 months.

For those who do survive, the disease evolves. Instead of excess calcium in the wrong places, bone growth becomes abnormal, leading to ARHR2. This condition manifests as rickets-like deformities, bowed legs, joint pain and progressive loss of mobility. Many affected individuals also experience hearing loss due to calcifications in the ear bones. Over time, patients suffer from chronic pain, fatigue and other complications.

“The biggest challenge with all these rare diseases is that many physicians have never seen a patient and they don’t know how to diagnose the patient,” Treco says.

Inozyme Pharma is focused on raising awareness among healthcare providers and families, ensuring that at-risk newborns undergo genetic testing. Since some cases can be detected via prenatal ultrasound, early intervention is critical.

Currently, no cure exists, and treatment options are limited to supportive care like phosphate and vitamin D supplementation. However, through ongoing research, physician education and patient advocacy, Inozyme Pharma aims to transform the treatment landscape for GACI and ARHR2, offering hope to families affected by these devastating conditions.

For families affected with GACI and ARHR2, Treco recommends GACI Global, a nonprofit organization whose mission is to connect families to each other and to the medical community.