TY - JOUR
T1 - hMaxi-K gene transfer in males with erectile dysfunction
T2 - Results of the first human trial
AU - Melman, Arnold
AU - Bar-Chama, Natan
AU - McCullough, Andrew
AU - Davies, Kelvin
AU - Christ, George
PY - 2006/12
Y1 - 2006/12
N2 - Eleven patients with moderate to severe erectile dysfunction (ED) were given a single-dose corpus cavernosum injection of hMaxi-K, a "naked" DNA plasmid carrying the human cDNA encoding hSlo (for human slow-poke), the gene for the α, or pore-forming, subunit of the human smooth muscle Maxi-K channel. Three patients each were given 500,1000, and 5000 μg, and two patients were given 7500 μg, of hMaxi-K and monitored for 24 weeks. The primary objectives of this phase I study were safety and tolerability of escalating hMaxi-K doses as assessed by clinical evaluations and laboratory tests. Secondary efficacy objectives were measured primarily by use of the International Index of Erectile Function (IIEF) scale. Patient responses were validated by partner responses. There were no serious adverse events and no dose-related adverse events attributed to gene transfer for any patient at any dose or study visit. No clinically significant changes from baseline were seen in physical evaluations (general and genitourinary), hematology, chemistry, and hormone analyses, or in cardiac events evaluated by repeated electrocardiograms. Importantly, no plasmid was detected in the semen of patients at any time after the injections. Patients given tlie two highest doses of hMaxi-K had apparent sustained improvements in erectile function (EF) as indicated by improved HEF-EF domain scores over the length of the study. One patient given 5000 μg and one given 7500 μg reported EF category improvements that were highly clinically significant and were also maintained through the 24 weeks of study. Efficacy conclusions cannot be drawn from results of a phase I trial with no control group. However, the promising primary safety outcomes of the study and preliminary indications of effectiveness provide evidence that hMaxi-K gene transfer is a viable approach to the treatment of ED and that further studies investigating the efficacy of hMaxi-K in patients with ED should be performed.
AB - Eleven patients with moderate to severe erectile dysfunction (ED) were given a single-dose corpus cavernosum injection of hMaxi-K, a "naked" DNA plasmid carrying the human cDNA encoding hSlo (for human slow-poke), the gene for the α, or pore-forming, subunit of the human smooth muscle Maxi-K channel. Three patients each were given 500,1000, and 5000 μg, and two patients were given 7500 μg, of hMaxi-K and monitored for 24 weeks. The primary objectives of this phase I study were safety and tolerability of escalating hMaxi-K doses as assessed by clinical evaluations and laboratory tests. Secondary efficacy objectives were measured primarily by use of the International Index of Erectile Function (IIEF) scale. Patient responses were validated by partner responses. There were no serious adverse events and no dose-related adverse events attributed to gene transfer for any patient at any dose or study visit. No clinically significant changes from baseline were seen in physical evaluations (general and genitourinary), hematology, chemistry, and hormone analyses, or in cardiac events evaluated by repeated electrocardiograms. Importantly, no plasmid was detected in the semen of patients at any time after the injections. Patients given tlie two highest doses of hMaxi-K had apparent sustained improvements in erectile function (EF) as indicated by improved HEF-EF domain scores over the length of the study. One patient given 5000 μg and one given 7500 μg reported EF category improvements that were highly clinically significant and were also maintained through the 24 weeks of study. Efficacy conclusions cannot be drawn from results of a phase I trial with no control group. However, the promising primary safety outcomes of the study and preliminary indications of effectiveness provide evidence that hMaxi-K gene transfer is a viable approach to the treatment of ED and that further studies investigating the efficacy of hMaxi-K in patients with ED should be performed.
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U2 - 10.1089/hum.2006.17.1165
DO - 10.1089/hum.2006.17.1165
M3 - Article
C2 - 17134370
AN - SCOPUS:33845774784
SN - 1043-0342
VL - 17
SP - 1165
EP - 1176
JO - Human Gene Therapy
JF - Human Gene Therapy
IS - 12
ER -