Iron depletion induced by bloodletting and followed by rhEPO administration as a therapeutic strategy in progressive multiple sclerosis: a pilot, open-label study with neurophysiological measurements

Neurophysiol Clin. 2013 Dec;43(5-6):303-12. doi: 10.1016/j.neucli.2013.09.004. Epub 2013 Oct 26.


Objectives: To evaluate the concept that iron depletion (ID) induced by bloodletting and followed by recombinant human erythropoietin (rhEPO) administration could be a therapeutic strategy in progressive multiple sclerosis (PMS) and that it could be assessed by neurophysiological measurements.

Patients and methods: In four patients with PMS, bloodletting was performed until ID was induced, and then rhEPO was administered (300 UI/kg/week). The changes induced by the treatment were assessed by clinical scores, biological tests, and neurophysiological study of cortical excitability using transcranial magnetic stimulation techniques.

Results: The treatment was well tolerated except for muscle cramps and one popliteal vein thrombosis in a patient confined to chair. ID was obtained within 28 weeks and was associated with endogenous production of EPO. No bloodletting was further required during a six-month period after introduction of rhEPO. At the end of the follow-up (up to one year), fatigue and walking capacities tended to improve in two patients. Neurophysiological changes were characterized by an increased cortical excitability, including a decrease of motor thresholds and an enhancement of intracortical facilitation and cerebellothalamocortical inhibition.

Conclusions: The combined ID-rhEPO therapy could authorize a prolonged administration of rhEPO in PMS patients, able to modify cortical excitability of the glutamatergic and gabaergic circuits. These preliminary data are encouraging to design a larger, controlled therapeutical trial to assess the value of such a strategy to improve functional symptoms in PMS patients, and maybe to prevent axonal degeneration. Neurophysiological measurements based on cortical excitability studies could provide sensitive parameters to evaluate treatment-induced changes in this context.

Keywords: Axonal degeneration; Dégénérescence axonale; Erythropoietin; Excitability; Excitabilité; Fer; Iron; Multiple sclerosis; Progression; Sclérose en plaques; Érythropoïétine.

MeSH terms

  • Aged
  • Combined Modality Therapy
  • Erythropoietin / genetics
  • Erythropoietin / therapeutic use*
  • Evoked Potentials, Motor / physiology
  • Female
  • Humans
  • Iron / blood*
  • Male
  • Middle Aged
  • Motor Cortex / physiopathology
  • Multiple Sclerosis, Chronic Progressive / drug therapy
  • Multiple Sclerosis, Chronic Progressive / physiopathology
  • Multiple Sclerosis, Chronic Progressive / therapy*
  • Phlebotomy*
  • Pilot Projects
  • Recombinant Proteins / therapeutic use
  • Walking / physiology


  • Recombinant Proteins
  • Erythropoietin
  • Iron