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Understanding progeria and processing-deficient progeroid laminopathies (PDPL)

Learn more about what causes progeria and PDPL, and how to treat them once a diagnosis is confirmed.

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Progeria and PDPL:
premature aging diseases

Ultra-rare, genetic, and multisystemic, progeria and PDPL result in accelerated morbidity and mortality1,2

Though there are distinct differences, progeria, also known as Hutchinson-Gilford progeria syndrome (HGPS), and processing-deficient progeroid laminopathies (PDPL) are types of laminopathies that are often grouped together.3

Both diseases:

Have low prevalence rates

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In the United States, the prevalence of progeria is 1 in 20 million,1 and the prevalence of progeroid laminopathies, which include both processing-deficient and processing-proficient, is 1 in 36.4 million.4

Share disease pathophysiological processes

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Both diseases are caused by genetic mutations, with progeria caused by a single-point mutation in LMNA and PDPL caused by a constellation of mutations in LMNA and/or ZMPSTE24. These affect the same nuclear architecture pathway, resulting in accumulation of harmful excess progerin or progerin-like proteins, damaging tissues and multiple organs and leading to early mortality.1,3

Accelerate morbidity and mortality

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Cardiovascular manifestations are commonly seen in both progeria and PDPL, though the course of disease, select manifestations, and severity can vary between the two.4 In progeria, patients often experience accelerated atherosclerosis leading to cardiovascular disease, stroke, and early mortality primarily caused by heart failure at a mean age of 14.6 years.1

Image Ana Clara, 11, Brazil. Photo courtesy of The Progeria Research Foundation.

The underlying cause: persistent nuclear accumulation of progerin or progerin-like proteins1,3

Left untreated, the accumulation of progerin or progerin-like proteins supports the likelihood of progressive cardiovascular disease.1

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    Due to the genetic mutation(s) in progeria and PDPL, prelamin A, a protein crucial to many cellular functions, is enzymatically modified to form progerin.3,5

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    Increased accumulation of progerin (or a similar protein) inside cellular nuclei drives a cascade of cellular pathologies that negatively affect tissues and organs throughout the body.1,3

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    Zokinvy® prevents farnesylation and the subsequent accumulation of progerin or progerin-like proteins within cells.6 This accumulation impairs tissue repair functions and further damages cells as they age, which can lead to early mortality.1,3,7

Early diagnosis of progeria and PDPL allows for earlier, targeted intervention4

Once a diagnosis is confirmed, initiate Zokinvy immediately.

Image Meghan, 19, USA. Photo courtesy of The Progeria Research Foundation

Children appear normal at birth but start to develop symptoms during the first 12 to 18 months of life.4,8

Clinical evaluation of a child’s appearance

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  • Evaluation of height and weight (failure to thrive, typically during first year of life)8,9

  • Examination for distinct visible clinical features8

  • Assessment of vital signs4

Medical history and records

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  • Evidence of vascular dysfunction; early cardiac changes can manifest between 5 and 8 years of age, usually start after age 88,10

Genetic testing to detect LMNA or ZMPSTE24 mutations

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  • Offered by labs: www.ncbi.nlm.nih.gov/gtr/

  • The Progeria Research Foundation offers a genetic testing program through laboratories certified by Certified Laboratory Improvement Amendments (CLIA) and in collaboration with the treating physician

Learn How Zokinvy Works
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IMPORTANT SAFETY INFORMATION

Contraindications

ZOKINVY is contraindicated in patients taking:

  • Strong or moderate CYP3A inhibitors or inducers
  • Midazolam
  • Lovastatin, simvastatin, and atorvastatin

INDICATION AND USAGE

ZOKINVY is indicated in adult and pediatric patients 12 months of age and older with a body surface area (BSA) of 0.39 m2 and above:

  • To reduce the risk of mortality in Hutchinson-Gilford Progeria Syndrome (HGPS)
  • For the treatment of processing-deficient
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