Novel strategies for stimulating erythropoiesis and potential new treatments for anaemia

  title={Novel strategies for stimulating erythropoiesis and potential new treatments for anaemia},
  author={Iain C Macdougall and Kai-Uwe Eckardt},
  journal={The Lancet},

Updates on Novel Erythropoiesis-Stimulating Agents: Clinical and Molecular Approach

In this review, all clinical indications, side effects, challenges and notable points regarding EPO, rHuEPO, and other ESAs have also been addressed along with its molecular characterization, such as the modifications needed to optimize their rHu EPO biosynthesis.

Erythropoiesis-stimulating agents in renal medicine.

All ESAs are effective in correcting renal anemia and increasing hemoglobin levels, but the choice of which to use should also take into account their pharmacokinetics and pharmacodynamics, their administration route, and economic issues.

The (re)challenging question of erythropoiesis-stimulating agents inducing pure red cell aplasia.

  • S. SummersS. HoldsworthE. Sharples
  • Medicine
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
  • 2008
Pure red cell aplasia (PRCA), secondary to EPO, will form the basis of this review and involves the generation of anti-EPO antibodies (Abs) resulting in significant anaemia.

Erythropoietins: a common mechanism of action.

Cardiovascular effects of erythropoietin an update.


As might be expected with a genetic copy of the endogenous protein, EPO is highly effective in stimulating erythropoiesis, particularly in chronic renal failure, and has very low immunogenicity.

Erythropoietin after a century of research: younger than ever

  • W. Jelkmann
  • Biology, Medicine
    European journal of haematology
  • 2007
The demonstration of Epo‐R in non‐haematopoietic tissues indicates that Epo is a pleiotropic viability and growth factor, and the neuroprotective and cardioprotective potentials ofEpo are reviewed with a focus on clinical research.

Use of erythropoiesis-stimulating agents in patients with anemia of chronic kidney disease: overcoming the pharmacological and pharmacoeconomic limitations of existing therapies.

Use of ESAs in the management of anemia of CKD is associated with improved quality of life, increased survival, and decreased progression of renal failure, and some evidence suggests that ESAs have a cardioprotective effect.

Pathophysiology of anemia and erythrocytosis.




Human erythropoietin gene therapy for patients with chronic renal failure.

Implantation of dermal cores ex vivo transduced with human genes could eventually be used in the clinical setting to express therapeutic serum proteins like erythropoietin, but nonimmunogenic delivery system should be tested as gene vehicles.

CERA (Continuous Erythropoietin Receptor Activator): a new erythropoiesis-stimulating agent for the treatment of anemia.

Continuous Erythropoietin Receptor Activator (CERA), a third-generation molecule, incorporating a large polymer chain, has been developed and has an elimination half-life in humans that is considerably longer than the half- life of either epoetin or darbepoetIn alfa.

Preclinical Evaluation of Hematide™, a Novel Erythropoietic Receptor Agonist for the Treatment of Anemia Caused by Kidney Disease.

Hematide is a potent erythropoietin receptor agonist with prolonged half-life and slow clearance times and is anticipated that similar prolonged clearance will be observed in the clinic, potentially enabling dosing intervals of 3 to 4 weeks that may translate into improved patient convenience and compliance.

Derivatives of Erythropoietin That Are Tissue Protective But Not Erythropoietic

CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis at a potency and efficacy comparable to EPO.

Development and characterization of novel erythropoiesis stimulating protein (NESP)

Darbepoetin alfa (novel erythropoiesis stimulating protein, NESP, ARANESPTM, Amgen Inc, Thousand Oaks, CA), which was engineered to contain 5 N-linked carbohydrate chains, is currently being evaluated in human clinical trials for treatment of anaemia and reduction in its incidence.

Pharmacokinetics of novel erythropoiesis stimulating protein compared with epoetin alfa in dialysis patients.

The longer half-life of NESP is likely to confer a clinical advantage over Epoetin by allowing less frequent dosing in patients treated for anemia.

Gene electro‐transfer of an improved erythropoietin plasmid in mice and non‐human primates

Transduction can be improved in several animal models by application of electric pulses after DNA injection, and Naked DNA intramuscular injection is a safe approach for gene delivery; however, transduction levels show high inter‐individual variability in rodents and very poor efficiency in non‐human primates.

Long-term reversal of chronic anemia using a hypoxia-regulated erythropoietin gene therapy.

It is established that a hypoxia regulatory mechanism similar to the natural mechanism can be achieved, and it makes EPO gene therapy more attractive and safer in clinical settings and it envisage that this control system will allow regulated delivery of therapeutic gene products in other ischemic settings.

Long-term pharmacologically regulated expression of erythropoietin in primates following AAV-mediated gene transfer.

Data indicate that one-time or infrequent gene transfer followed by dimerizer regulation is a promising approach for delivery of therapeutic proteins.