Pyruvate Kinase Deficiency (PKD)

Pyruvate kinase deficiency (PKD) is an inherited disorder resulting from the lack of the enzyme pyruvate kinase which participates in glycolysis and energy metabolism in the erythrocytes. Protheragen's extensive experience in PKD therapy development places us in a unique position to offer specific guidance that extends from PKD therapy research to the market launch.

Overview of Pyruvate Kinase Deficiency (PKD)

Pyruvate kinase deficiency (PKD) is the most common form of genetic nonspherocytic hemolytic anemia due to autosomal recessive mutations in PKLR gene which is responsible for erythrocyte specific pyruvate kinase (PK-R) enzyme. With its prevalence as 1 in 20,000 Northern Europeans, PKD presents with chronic hemolysis that can severely range from compensated anemia to needing transfusions frequently.

Fig.1 The physiopathology of pyruvate kinase deficiency (PKD), and its clinical features and complications. (Fattizzo B, et al., 2022)

Pathogenesis of Pyruvate Kinase Deficiency (PKD)

Pyruvate kinase deficiency (PKD) is caused by inherited mutation from the PKLR gene which leads to low erythrocyte pyruvate kinase activity which disrupts glycolysis to deplete ATP and accumulate 2,3-BPG. This form of metabolic crisis leads to rigid, dysfunctional red blood cells that undergo splenic sequestration (extravascular hemolysis) or mechanical destruction (intravascular hemolysis), while chronic tissue starvation of oxygen evokes compensative erythroid hyperplasia.

Fig.2 Pyruvate kinase deficiency (PKD) results in decreased ATP production and accumulation of pyruvate kinase proximal pathway intermediates. (Al-Samkari H, et al., 2020)

Therapy Development for Pyruvate Kinase Deficiency (PKD)

Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.

Our Services

Protheragen devotes its services towards accelerating the discovery of new treatments for anemias, with special focus on pyruvate kinase deficiency (PKD). Our fully integrated services include creation of diagnostics, development of innovative therapies, precision disease modeling, and thorough preclinical validation. We gap the divide between clinical research and practice with the use of proprietary technologies and validated PKD-specific models, allowing our partners to proceed with their therapies from research to commercial application.

Therapeutic Development Services

As a premier provider of therapeutic development solutions, Protheragen is dedicated to pioneering a diverse range of groundbreaking therapies for hairy cell leukemia (HCL) aimed at tackling the intricate obstacles within this domain.

• Small Molecule Drug Development
• Cell Therapy Development
• Gene Therapy Development

• Therapeutic Antibody Development
• Therapeutic Peptide Development
• Therapeutic Protein Development

Animal Model Development Services

Protheragen delivers genetically engineered PKD animal models that faithfully recapitulate human disease pathophysiology, enabling robust preclinical evaluation of novel therapies.

• Spontaneous Model: Our scientists discovered that pups of the CBA strain of inbred mice spontaneously developed splenomegaly accompanied by severe anemia.
• Transgenic Model: The model was engineered through gene editing-mediated PKLR knockout combined with human PKLR mutation knock-in, creating a humanized disease model.

At Protheragen, we are committed to validating and optimizing therapies for pyruvate kinase deficiency (PKD) through preclinical studies including pharmacodynamics (PD), pharmacokinetics (PK) and toxicology to ensure their successful regulatory approval. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.

References

• Fattizzo B, Cavallaro F, Marcello A P M L, et al. Pyruvate kinase deficiency: current challenges and future prospects[J]. Journal of Blood Medicine, 2022: 461-471.
• Al-Samkari H, Van Beers E J, Kuo K H M, et al. The variable manifestations of disease in pyruvate kinase deficiency and their management[J]. haematologica, 2020, 105(9): 2229.