LAPS-FSH: a new and effective long-acting follicle-stimulating hormone analogue for the treatment of infertility
Sunyoung Jung A B D , Youngjin Park C D , YoungHoon Kim C , Yu Yon Kim C , Hyun-Ji Choi A B , Woo-Chan Son A B E and SeChang Kwon C E
+ Author Affiliations
- Author Affiliations
A Department of Pathology, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea.
B Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea.
C Hanmi Research Center, Hwaseong-si, Gyeonggi-do, 445-813, Korea.
D The authors consider that the first two authors should be regarded as joint first authors.
E Corresponding authors. Emails: ksc3397@hanmi.co.kr; wcson32@hanmail.net
Reproduction, Fertility and Development 26(8) 1142-1153 https://doi.org/10.1071/RD13118
Submitted: 13 April 2013 Accepted: 15 August 2013 Published: 18 September 2013
Abstract
Although several long-acting follicle-stimulating hormone (FSH) therapies have been developed to enhance the ovarian response, a disadvantage of FSH therapy is its relatively short half-life, which requires women to receive one to two injections per day for almost 2 weeks. In the present study, we developed a novel FSH analogue by conjugating recombinant human FSH (rhFSH) and the constant region of the human immunoglobulin G4 fragment via non-peptidyl linkers. The efficacy of the FSH analogue was evaluated in vitro by cAMP level assessments, pharmacokinetic studies and a determination of ovarian weight and by comparing these findings with the results from other FSH analogues. In addition, the total number of antral and Graafian follicles was determined after 7 days of treatment with control, 6 µg kg–1 follitropin β, 6, 12 or 42 µg kg–1 corifollitropin α or 3, 6 or 12 µg kg–1 long acting protein/peptide discovery-follicle-stimulating hormone (LAPS-FSH). As a result, the animals treated with 12 µg kg–1 LAPS-FSH produced additional and larger healthy follicles. These data demonstrate that LAPS-FSH promotes growth and inhibits atresia of the ovarian follicle compared with other available drugs, suggesting that our new drug enhances the efficacy and duration of treatment. It is expected that our new FSH analogue will result in a higher chance of pregnancy in patients who are unresponsive to other drugs.
Additional keywords: fertility drug, Graafian follicles, immunoglobulins, ovulation, pregnancy.
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