ORLANDO, May 22 — The next generation of therapy for erectile dysfunction could include semiannual intracavernosal injections of a gene that improves smooth muscle function, preliminary clinical results suggest.
A single injection of hMaxi-K led to restoration of normal erectile function that lasted for six months in two men treated with the highest dose, Arnold Melman, M.D., of Albert Einstein College of Medicine in New York, reported here at the American Urological Association meeting.
“The results were exactly as we had predicted from our animal studies,” said Dr. Melman. “If these findings hold up in further clinical investigations, we think men will require two injections a year to maintain normal sexual function.”
Two-year follow-up of the first 11 men treated has raised no safety concerns related to the gene transfer therapy, he added, although one patient was lost to follow-up.
The therapy evolved from recognition that abnormal smooth muscle function plays a major role in erectile dysfunction.
Dr. Melman said hMaxi-K consists of a naked DNA plasmid vector carrying human cDNA encoding a subunit of the smooth muscle potassium ion channel. The therapy stimulates endogenous protein production to correct abnormalities in smooth muscle function.
“We’ve shown in other studies that there is either a reduction in the amount of potassium channel present on the cell membrane or splice variants that don’t work as effectively that are present in both aging and disease,” said Dr. Melman.
An initial phase I dose-escalation study of hMaxi-K involved 11 men with moderate to severe erectile dysfunction. The patients had shown no improvement with other therapies or had rejected other types of therapy.
Three men each received doses of 500, 1,000, and 5,000 ?µg of hMaxi-K, and two men received 7,500 ?µg, injected directly into the corpus cavernosum.
Pre- and posttreatment scores on the International Index of Erectile Function showed that the two men who received the highest dose of hMaxi-K had a return of normal erectile function for six months. At that point, erectile function regressed to pretreatment levels.
A companion study reported at the AUA meeting showed the gene therapy affects sexual behavior, as well as erectile function.
Male cynomolgus monkeys with atherosclerosis-related erectile dysfunction received the gene transfer therapy and then were placed with estrogen-implanted female monkeys.
Following treatment virtually every aspect of the male monkeys’ sexual function and behavior improved, said George Christ, Ph.D., of Wake Forest University in Winston-Salem, N.C., a co-developer of hMaxi-K.
The treatment influenced behaviors unrelated to erectile function, such as time spent grooming the female and decreased frequency of body contact, typical of the postmating period of most macaque species.
“The therapy seemed to improve the males’ overall sense of well being,” said Dr. Christ. “They felt better about themselves.”
A phase1b clinical evaluation of three higher doses of hMaxi-K is expected to end by early June.
The potassium ion channel gene therapy has potential application in a variety of conditions involving smooth muscle dysfunction, said Dr. Melman. An initial clinical trial of patients with overactive bladder has already begun.
Drs. Melman and Christ are founders and remain principals in Ion Channel Innovations, the company that is developing the gene-transfer therapy.
Primary source: Journal of Urology
Melman A, et al “Long-term safety follow-up of a phase 1 trial for gene transfer therapy of ED with hMaxi-K” J Urol 2008; 179(suppl): 426; Abstract 1241.