5-androstenediol improves survival in clinically unsupported rhesus monkeys with radiation-induced myelosuppression.
We previously reported that five daily intramuscular doses of 5-androstenediol (AED), a naturally occurring adrenal steroid hormone, stimulated multilineage recovery of bone marrow in rhesus monkeys with radiation-induced myelosuppression after 4.0 Gy total body irradiation (TBI). Here we report the effect of AED on the survival of eighty rhesus macaques that received a 6.0 Gy dose of TBI in four sequential pilot studies. The drug was administered intramuscularly, based on body weight, 2-4 h after irradiation and continued once daily for a total of five injections. No clinical support in the form of antibiotics or transfusions was given to the animals at any time during the study. Five of the 40 (12.5%) treated animals died, compared to 13 of 40 (32.5%) of the animals in the control group (p=0.032). The combination of accumulated days of thrombocytopenia (<20,000 platelets/microL) up to day 14 (before the first death) together with treatment, accurately predicts mortality (p<0.001). The compound significantly reduced the duration of thrombocytopenia and neutropenia (p<0.01). The accumulation of days of neutropenia (ANC<500 cells/microL) up to day 14 plays no major role in predicting death. AED shows significant activity in irradiated primates with acute hematopoietic radiation syndrome.
Stickney
Dwight R
DR
Hollis-Eden Pharmaceuticals Inc, San Diego, CA 92121, USA. dstickney@holliseden.com
Dowding
Charles
C
Authier
Simon
S
Garsd
Armando
A
Onizuka-Handa
Nanette
N
Reading
Christopher
C
Frincke
James M
JM
D015114:Androstenediol / Q000494:pharmacology*; D000818:Animals; D005260:Female; D005720:Gamma Rays; D008253:Macaca mulatta; D008297:Male; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000401:mortality; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013921:Thrombocytopenia / Q000188:drug therapy / Q000401:mortality; D014965:X-Rays
D011837:Radiation-Protective Agents; D015114:Androstenediol