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21/10/2019 8:17 am
Development of a Long Acting Erythropoietin by Fusing the Carboxyl-Terminal Peptide of Human Chorionic Gonadotropin Subunit to the Coding Sequence of Human Erythropoietin
Fuad Fares*, Sherif Ganem, Taleb Hajouj, and Ester Agai
Faculty of Science, University of Haifa, Haifa, 31905, and ModigeneTech, Weizmann Science Park, Nes-Ziona, 74140, Israel
* To whom correspondence should be addressed. E-mail: [email protected].
Human erythropoietin (EPO) is a glycoprotein hormone secreted from the kidney and controls red blood cell production. EPO has a wide clinical use in the treatment of anemia associated with renal disease, certain chronic diseases and anemia related to chemotherapy and radiotherapy. One major issue regarding the clinical use of EPO is its relatively short half-life due to its clearance by glomerular filtration. Thus the therapeutic protocol used in the treatment of patient required frequent injections of EPO. To address this issue, we constructed a chimeric gene that contains the sequence of the carboxyl-terminal peptide (CTP) of human chorionic gonadotropin (HCG) subunit bearing four O-linked oligosaccharide recognition sites and the coding sequence of human EPO cDNA. Fusing the CTP to the carboxyl-terminal of EPO did not affect secretion, receptor binding affinity or in vitro bioactivity. However, both in vivo potency and half-life of EPO-CTP were significantly enhanced. A single injection dose (660 IU/kg) of EPO Wild-type (EPO-WT) administered once a week had no significant effect on haematocrit levels. However, EPO-CTP administered as a 660 IU/kg once a week was effective as well as the same total dose of EPO-WT administered as 220 IU/kg 3 times a week. This may emphasize the importance of sustained blood levels rather than total dose of administration for in vivo bioactivity. These data established the rational for using this chimera as a long-acting EPO analog. The therapeutic efficacy of EPO-CTP analog needs to be established in higher animals and in human clinical trials.
21/10/2019 8:48 am
great info
21/10/2019 9:12 am
JB has plenty of good info! A literal gold mine throughout the years.
RG
21/10/2019 9:34 am
but where'd we get it?
21/10/2019 10:02 am
Seems to suggest that with currently available EPO that there may be some basis for lower doses on an EOD basis being as effective as mega loading doses. May take a bit longer to reach target but possibly with fewer IUs of EPO. I'm currently finding this to be the case in my cycle. I started loading with 24k and 18k the first two weeks and have now found I get relatively the same response from 3 to 4k EOD. I guess it just depends on how long you have to reach targe and what your goals are going in. Anyone else experience this?
21/10/2019 10:18 am
I think the chimeric EPO/CTP protein would be better for athletes on a budget that can't afford normal EPO because of the smaller doses, but with the increased stability of the protein will increase the testers ability to find it in urine/blood (even with the smaller doses)
Even Tyler wouldn't be able to find an explanation for a positive test with this guy...except for mayby a vanishing catalyst that is responsible for the endogenous fusion of the CTP/EPO .