Cyclic neutropenia occurs in humans and grey collie dogs, is characterized by recurrent neutropenia and is treated by repeated injections of recombinant granulocyte colony stimulating factor (rG-CSF). As dose escalation of lentivirus may be clinically necessary we monitored the outcome of four sequential intramuscular injections of G-CSF-lentivirus of 3×107 infectious units per Kg of body weight to a normal dog and a grey collie. In the normal dog absolute neutrophil counts were significantly increased after each dose of virus with mean levels of 27.75±3.00; 31.50±1.40; 35.05±1.68, 43.88±2.94 x103 cells/µl respectfully (p<0.001) and elevated neutrophil counts of 31.18±7.81 x103 cells/µl were maintained for over 6 years with no adverse effects. A grey collie dog with a mean count of 1.94±1.48 x103 cells/µl received G-CSF-lentivirus and we observed sustained elevations in neutrophil levels for over 5 months with a mean of 26.00±11.00×103 cells/µl, significantly increased over pretreatment level (p<0.001). Following the second and third virus administration mean neutrophil counts of 15.80±6.14 and 11.52±4.90×103 cells/µl were significantly reduced over cell counts following the first virus administration (p<0.001). However, following the 4th virus administration mean neutrophil counts of 15.21±4.50×103 cells/µl were significantly increased over the previous virus (p<0.05). Throughout the nearly 3 years of virus administrations the dog gained weight, was healthy and showed neutrophil counts significantly higher than pretreatment levels (p<0.001). These studies suggest that patients with cyclic and other neutropenias may be treated by escalating doses of G-CSF-lentivirus to obtain a desired therapeutic neutrophil count.
Dr. Ofer Yanay, Dr. David Dale, and Prof. William R Osborne. Human Gene Therapy