Studying ENPP1 Deficiency
(GACI or ARHR2)
Now enrolling patients with ENPP1 Deficiency (GACI or ARHR2) in an observational study or the first clinical trial for a potential new treatment. With your participation, healthcare providers can better understand this disease. You can also help inform possible future treatment options.

Join our research!

About ENPP1 deficiency

ENPP1 Deficiency is a rare and life-threatening genetic disorder caused by mutations in the ENPP1 gene1

ENPP1 Deficiency leads to a low amount of pyrophosphate (PPiA substance made by the body to control mineral buildup in soft tissues)2

This causes a disease that could affect the entire body3

The clinical signs of ENPP1 deficiency may first appear from the

fetal stage through adulthood, and include3:

Neointimal proliferation: thickening of the arterial wall leading to stiffness of the artery

Ectopic mineralization: calcification of the arteries, organs, and joints

Pathological skeletal mineralization: under-mineralization of bones

The time of onset and symptoms of ENPP1 Deficiency vary widely3

Early symptoms
  • Heart failure, respiratory problems, hypertension, heart attack, neurological problems (stroke, seizure)
Symptoms in children
  • Skeletal deformities, short stature, severe bone pain, bone fractures, hearing loss, neurological problems (stroke, seizure)
Symptoms in adults
  • Severe bone and joint pain, fatigue, muscle weakness, bone fractures, loss of mobility, hypertension
People living with ENPP1 Deficiency have been diagnosed with:
  • Neointimal proliferationThickening of the artery wall due to the growth of smooth muscle and/or mineralizationBuildup of different minerals in the body and/or of the aorta, arteries, joints, and major organs (eg, heart and kidneys)
  • Organs can start to fail or not work properly
  • Soft and deformed bones due to undermineralization
  • This can lead to severe skeletal defects, short height, bone pain, and a greater risk of bone breaks

People with ENPP1 Deficiency have a high risk of death early in life. Those who survive face many health issues.3,6 If you think that you may have ENPP1 Deficiency but your diagnosis has not been confirmed, consider getting a no‑charge genetic test to verify.

The ENPP1 Deficiency Prospective Observational Study

The ENPP1 Prospective Observational Study is designed to look at how ENPP1 Deficiency presents and progresses from birth through adulthood. The study will include people across all age groups.

Researchers will follow participants over time to:

  • Map the course of ENPP1 Deficiency
  • Understand how PPi levels and other markers or outcomes can change
  • Gain insights to help diagnose and treat ENPP1 Deficiency


Participation in this study could help scientists better understand the disease and inform possible future treatment options.

Participants must be:
  • Diagnosed with ENPP1 Deficiency (all age groups) or ABCC6 Deficiency (infantile onset) through genetic testing, clinical presentation, radiologic, or biochemical testing
  • Able to provide written consent by themselves or through a legal caregiver before research
  • Have a PPi level at screening that meets the requirement
  • Willingness to provide relevant medical records and complete all aspects of the study
If enrolled, participants will complete a number of tests and visits throughout the study. These tests and visits may be time-consuming and/or require assistance from a caregiver. A researcher will thoroughly explain all requirements before enrollment.
If you have a confirmed ENPP1 (all age groups) or ABCC6 (infantile onset) diagnosis, please see additional information about study enrollment. Otherwise, keep reading to see how you can get tested for ENPP1 or ABCC6 Deficiency.

The Clinical Trial for ENPP1 Deficiency

The clinical trial for ENPP1 Deficiency will determine if a new medication, INZ-701, is suitable to treat those affected with the disease. Participants will be split into 3 groups. Each group will receive a different dose of INZ-701. Every 4 weeks, the dose given will increase if it is deemed safe to do so. INZ-701 is a subcutaneous injection (under the skin).

Researchers will monitor participants on increasing doses of INZ-701 to:

  • Understand the safety of the medication
  • Study how the medication is processed throughout the body
  • Study changes in PPi and other markers

For the extension period of the study, researchers will monitor participants on increasing doses of INZ-701 to evaluate skeletal, vascular, and physical function as well as outcomes reported by participants.

Subject participation consists of a screening period, a 32-day dose-evaluation period, and a 48-week extension period following completion of the dose-evaluation period.

Participants must:
  • Provide written or electronic consent after the nature of the study has been explained, and prior to any research-related procedures
  • Be diagnosed with ENPP1 Deficiency supported by prior genetic identification of biallelic ENPP1 mutations
  • Be male or female, 18 to < 65 years old at screening
  • Have a PPi level at screening that meets the requirement
  • Be willing and able to complete all aspects of the study in the opinion of the researcher
  • Agree to provide access to relevant medical records
People being treated with statins or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors must:
  • Be on stable doses for 3 years prior to enrollment through end of study unless previously cleared
Women of child-bearing potential must:
  • Have a negative serum pregnancy test at screening
Women of child-bearing potential and partners of fertile males who are of child-bearing potential must agree to:
  • Use 1 highly effective form of contraception and a barrier method from at least 1 month before the first dose through 30 days after last dose of treatment
  • Not donate ova from the period following the first dose through 30 days after last dose of treatment
Males who are sexually active must agree to:
  • Use condoms from the period following first dose through 30 days after the last dose of treatment
  • Not donate sperm from the period following the first dose through 30 days after last dose of treatment

If you have a confirmed ENPP1 diagnosis and meet the criteria described, please see additional information about study enrollment. Otherwise, keep reading to see how you can get tested for ENPP1 Deficiency.

Contacts
Inozyme Clinical Trial Information
1-857-330-4340
clinicaltrials@inozyme.com

Locations
United States, New Jersey
Clinilabs Recruiting
Eatontown, New Jersey, United States, 07724
Contact: Imani Beard
1-212-994-4567
Ext. 6472
Contact: Ziomara Spoelstra
1-646-625-5524

Coming Soon
London, United Kingdom
Richmond Pharmacology
Contact: Keith Berelowitz
k.berelowitz@richmondpharmacology.com

Additional clinical trial information is coming soon.
Please visit the website often for an update.

ABOUT ABCC6 DEFICIENCY

ABCC6 Deficiency is a rare, life-threatening, and progressively debilitating genetic disorder caused by mutations in the ABCC6 gene7

ABCC6 Deficiency leads to a low amount of pyrophosphate (PPiA substance made by the body to control mineral buildup in soft tissues)8

This causes a disease that could affect the entire body7

The clinical sign of ABCC6 Deficiency is7:

Ectopic mineralization: calcification of the elastic fibers affecting the skin, eyes, and blood vessels

Symptoms of ABCC6 Deficiency progress9

0-12 months
Early symptoms8
  • Some infants with ABCC6 Deficiency are diagnosed with a vascular calcificationMineral deposits on the walls of arteries and veins condition resembling the acute infantile form of ENPP1 Deficiency.
Icon of person
15-30 years
Symptoms that can appear from adolescence through adulthood7
  • Dermatologic changes (changes in the skin)
    • Yellowish bumps called papules
  • Ocular changes
    • Angioid streaks
Icon of person
30 years and above
Symptoms that appear in adulthood7
  • Cardiovascular issues
    • Peripheral arterial disease: pain and cramping in legs
    • Stroke
  • Pain
  • Skin calcification lesions (calcium deposits that appear as hard bumps)
  • A recent report stated that 37% of PXE patients over the age of 50 experienced visual impairment and 15% were legally blind10

ABCC6 Deficiency studies coming soon

People living with ABCC6 Deficiency have been diagnosed with:
  • Neointimal proliferationThickening of the artery wall due to the growth of smooth muscle and/or mineralizationBuildup of different minerals in the body and/or of the aorta, arteries, joints, and major organs (eg, heart and kidneys)
  • Organs can start to fail or not work properly
  • Calcification (mineral deposits) of soft connective tissues including the eyes, cardiovascular (heart and blood system), and skin

The Genetic Testing Process

Consider getting tested for ENPP1 Deficiency if you’ve experienced the symptoms described or have been diagnosed with GACI and/or ARHR2

Individuals who meet the eligibility criteria for the testing program can receive a no-cost, third-party genetic test to determine if they have the condition or are a carrier for ENPP1 Deficiency. Those with confirmed ENPP1 status may be eligible to participate in studies to help researchers better understand and treat the condition, including the ENPP1 Deficiency Prospective Observational Study previously mentioned.

Your healthcare provider (HCP) will determine if you meet eligibility criteria for a no-cost genetic test through this program.

Your HCP will order your test by following the instructions.

The genetic test will be processed at a genetic laboratory; the results will be sent to your HCP in 2-3 weeks (on average), who will discuss the results with you.
Your HCP can contact PreventionGenetics at 1‑715‑387‑0484 and/or email clinicaldnatesting@preventiongenetics.com or visit this website.

For more information, including FAQs: 

  • ABCC6, ATP binding cassette transporter protein subfamily C member 6; ENPP1, ectonucleotide pyrophosphatase/phosphodiesterase 1.

References

  1. Ferreira C, Ziegler S, Gahl WA. Generalized arterial calcification of infancy. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; 2014.
  2. Kalal IG, Seetha D, Panda A, Nitschke Y, Rutsch F. Molecular diagnosis of generalized arterial calcification of infancy (GACI). J Cardiovasc Dis Res. 2012;3(2):150-154.
  3. Ziegler SG, Gahl WA, Ferreira CR. Generalized Arterial Calcification of Infancy. 2014 Nov 13 [Updated 2020 Dec 30]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021.
  4. Nitschke Y, Baujat G, Botschen U, et al. Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6. Am J Hum Genet. 2012;90(1):25-39.
  5. Nitschke Y, Rutsch F. Generalized arterial calcification of infancy and pseudoxanthoma elasticum: two sides of the same coin. Front Genet. 2012;3:302.
  6. Rutsch F, Böyer P, Nitschke Y, et al. Hypophosphatemia, hyperphosphaturia, and bisphosphonate treatment are associated with survival beyond infancy in generalized arterial calcification of infancy. Circ Cardiovasc Genet. 2008;1(2):133-140. doi:10.1161/CIRCGENETICS.108.797704.
  7. Moitra K, Garcia S, Jaldin M, et al. ABCC6 and Pseudoxanthoma Elasticum: The face of a rare disease from genetics to advocacy. Int J Mol Sci. 2017;18(7):1488. Published 2017 Jul 11. doi:10.3390/ijms18071488.
  8. Germain DP. Pseudoxanthoma elasticum. Orphanet J Rare Dis. 2017;12(1):85. Published 2017 May 10. doi:10.1186/s13023-017-0639-8.
  9. Klement JF, Matsuzaki Y, Jiang QJ, et al. Targeted ablation of the abcc6 gene results in ectopic mineralization of connective tissues. Mol Cell Biol. 2005;25(18):8299-8310. doi:10.1128/MCB.25.18.8299-8310.2005.
  10. Risseeuw S, Ossewaarde-van Norel J, Klayer CCW, Colijn JM, Imhof SM, van Leeuwen R. Visual acuity in pseudoxanthoma elasticum. Retina. 2019;39(8):1580-1587.