Therapeutic protein for thalassemia Bushra Abbas Haani Shazad Zainab Ashfaq Ahtasham Danish

Thalassemia Mutation on chromosome 11[β][mutations] and 16[α][deletions] Excess α and β chains precipitate as inclusion bodies Intra medullary cells will have ineffective erythropoiesis Extra medullary cells will have hemolysis

Any treatment possible is only for the β Thalassemia [major or minor] For α Thalassemia no effective treatment – Fatal in any case

Erythropoietin (EPO)- Glcoprotein hormone Used for treating anemia in β Thalassemia Recombinant human Epo (rHuEpo)- first hematopoietic growth factor produced by GE Stimulating effect on RBC production-normally released by hypoxia in kidneys Triggers differentiation of erythroid progenitor cells

Advantages Available in form of injections Improved erythrypoiesis *Stimulates fetal hemoglobin production  Fetal hemoglobin benefits:  Different sequence so no faulty protein from faulty gene  Fetal Hb has greater affinity for binding with O 2 - varrying globin chains [Hb F and Hb A]

Suppliers Roche Pharmaceuticals Karachi Medipak Limited, Lahore Hoffmann Human Health Pak. Ltd. Lahore Highnoon Laboratories, Lahore *All these pharmaceuticals import EPO produced in either Korea or China.

Limitations Faulty gene means faulty new cells from bone marrow-rendered ineffective in such cases Weakness, fatigue, short of breath, if skin looks pale, these may be signs that body has stopped responding to this medication.

Azacitidine Azacitidine is 4-amino-1-β-D-ribofuranosyl-s-triazin. Chemical stability is high upto 48 hrs. when stored protected from light at 2-8 °C.

Mechanism Demethylation agent Used to treat conditions where bone marrow cannot produce new cells Kills the abnormal cells and triggers healthy cell production in bone marrow Restores normal function to genes for normal proliferation Injections available

Advantages Reduces blood transfusion needs Does not affect normal DNA synthesis Fetal hemoglobin modifier

Table 6: Effect of Azacitidine on RBC Transfusions in MDS Patients

Sides effects Adverse reactions (Gastrointestinal or nervous disorders, Blood and lymphatic system, Infections) Hepatotoxicity Renal failure Carcinogenesis Mutagenesis Impairment Of Fertility Nausea, Vomiting, Constipation, Weakness, Chills or shivering

Combination Therapy EPO + Azacitidine Azacitidine gets rid of faulty cells Azacitidine and EPO both trigger fetal hemoglobin production Fetal hemoglobin gene completely healthy EPO triggers the production of these healthy fetal hemoglobin cells

QUESTIONS? THANK YOU