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PPi, or pyrophosphate, is a metabolite that regulates calcification, which is the complicated process of regulating calcium in the body. Calcium is transported through the bloodstream and found in every cell, so calcification can occur anywhere. If there is a PPi deficiency, or low PPi, calcium can build up too much or not enough.
In certain rare, life-threatening, and devastating genetic disorders, PPi levels are below the normal levels. These low levels can lead to over-mineralization of soft tissues and/or under-mineralization of bone, which cause damage and disease to bones, arteries, and organs.
Our founders recognized the integral role that low PPi plays in a broad range of rare calcification disorders that threaten and limit life. Based on this knowledge, our scientists created and tested INZ-701, an enzyme replacement therapy designed to increase PPi levels and regulate calcification in multiple metabolic diseases, including ENPP1 Deficiency and ABCC6 Deficiency.
Key Genes Implicated in PPi Deficiency
Two genes, ENPP1 and ABCC6, regulate PPi levels in the blood. Mutations in these genes are linked to calcification disorders resulting from low PPi.
|Genes||Disorders||What it Stands For|
|ENPP1 gene||ENPP1 Deficiency||Ectonucleotide Pyrophosphatase/Phosphodiesterase 1|
|ABCC6 gene||ABCC6 Deficiency||Adenosine triphosphate [ATP] binding cassette transporter protein subfamily C member 6|
Disorders of PPi Deficiency
The disorders resulting from a mutation in the ENPP1 gene include:
- In babies with generalized arterial calcification of infancy (GACI), calcium builds abnormally in the walls of blood vessels, often resulting in death by six months of age.
- In people with autosomal recessive hypophosphatemic rickets type 2 (ARHR2), low PPi can lead to severe muscle/bone/joint pain, limited movement of the spine and hips, short stature, and often bowed legs or knocked knees.
The disorders resulting from a mutation in the ABCC6 gene include:
- In people with pseudoxanthoma elasticum (PXE), calcium deposits form in the tissue, often resulting in changes in the skin, eyes, cardiovascular system, and gastrointestinal system.
- Similar to GACI type 1, in people with GACI type 2, calcification leads to narrowing of large and medium-sized arteries, often resulting in heart failure and death by six months of age.