TY - JOUR
T1 - TNP-470 is an effective antimicrosporidial agent
AU - Coyle, Christina
AU - Kent, Michael
AU - Tanowitz, Herbert B.
AU - Wittner, Murray
AU - Weiss, Louis M.
N1 - Funding Information:
Received 10 July 1997; revised 19 September 1997. Grant support: NIH (AI-31788); TAP Holding Inc. Reprints or correspondence: Dr. Louis M. Weiss, Albert Einstein College of Medicine, 1300 Morris Park Ave., Room 504, Forchheimer, Bronx, NY 10461 (lmweiss@aecom.yu.edu).
PY - 1998
Y1 - 1998
N2 - Therapy for microsporidia, which cause diarrhea and a wasting syndrome in persons with AIDS, has had limited success. Fumagillin, a naturally secreted water-insoluble antibiotic, has in vitro activity against microsporidia and has been used successfully in the treatment of superficial keratitis in patients with AIDS, but systemic therapy has been limited by toxicity of the currently available fumagillin salt. TNP-470, a semisynthetic analogue of fumagillin, was studied in vitro and in the athymic nude mouse model of microsporidiosis. RK13 cells were infected with microsporidia of the family Encephalitozoonidae and treated at day 3 with TNP-470. This agent was highly effective, with an ID50 (50% inhibitory dose compared with control) of 0.001 μg/mL. TNP-470 also demonstrated in vivo activity against Encephalitozoon cuniculi, with prolonged survival and the prevention of the development of ascites in infected athymic mice. These data suggest that the fumagillin derivative TNP-470 is a promising agent for the treatment of microsporidiosis.
AB - Therapy for microsporidia, which cause diarrhea and a wasting syndrome in persons with AIDS, has had limited success. Fumagillin, a naturally secreted water-insoluble antibiotic, has in vitro activity against microsporidia and has been used successfully in the treatment of superficial keratitis in patients with AIDS, but systemic therapy has been limited by toxicity of the currently available fumagillin salt. TNP-470, a semisynthetic analogue of fumagillin, was studied in vitro and in the athymic nude mouse model of microsporidiosis. RK13 cells were infected with microsporidia of the family Encephalitozoonidae and treated at day 3 with TNP-470. This agent was highly effective, with an ID50 (50% inhibitory dose compared with control) of 0.001 μg/mL. TNP-470 also demonstrated in vivo activity against Encephalitozoon cuniculi, with prolonged survival and the prevention of the development of ascites in infected athymic mice. These data suggest that the fumagillin derivative TNP-470 is a promising agent for the treatment of microsporidiosis.
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U2 - 10.1086/517390
DO - 10.1086/517390
M3 - Article
C2 - 9466552
AN - SCOPUS:0031929734
SN - 0022-1899
VL - 177
SP - 515
EP - 518
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 2
ER -
