New Research on recombinant granulocyte colony stimulating factor (rG-CSF) in Cyclic Neutropenia (Yanay, Dale and Osborn)


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.

Read More:

Repeated Lentivirus-mediated G-CSF Administration to Treat Canine Cyclic Neutropenia

Dr. Ofer Yanay, Dr. David Dale, and Prof. William R Osborne. Human Gene Therapy



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