Genes for impotence
The results were encouraging – none of the 11 volunteers suffering from erectile dysfunction had any side effects.
Any more or less sexually mature person has an idea of what an erection is. With knowledge of how it occurs, things are somewhat worse, and yet without them it is impossible to understand violations of this process and methods of their treatment.
An erection can occur in response to nerve impulses emanating from the brain during sexual arousal from information received by the senses, or pictures drawn by the imagination (psychogenic erection). In addition, an erection is caused by a simple mechanical irritation of the penis (reflex erection). At the same time, the central nervous system is practically not involved – nerve impulses are processed at the level of the sacral nerve plexus.
In both cases, the impulses cause the dilation of the arteries supplying blood to the penis, which leads to the filling of the cavernous bodies with blood. These bodies, which make up the bulk of the penis, significantly increase in size when filled and become hard – an erection occurs. For the normal development of the reproductive system, which provides an erection, a sufficient level of male sex hormones, in particular testosterone, is necessary.
If any link of this mechanism is violated, a disease called erectile dysfunction (ED) occurs. The outdated, but still common name of this disorder – impotence – comes from the Latin term impotentia coeundi, meaning the inability to insert the penis into the vagina.
All causes of erectile dysfunction are divided into two large groups: physiological and psychological. Physiological causes are associated with a violation of the direct mechanism of erection; they include blood supply disorders in atherosclerosis, vasculitis, diabetes mellitus, heart failure, etc., injuries to the cavernous bodies, nerve injuries during prostate surgery, hormonal disorders and some others. Psychological reasons are related to a person's thoughts and feelings.
Who 's into whatThe first known attempts to treat erectile dysfunction were made by Arab doctors in the Middle Ages.
In their arsenal there were dietary methods and medications, both for oral administration and for topical application and injection into the urethra.
In the Western world, the excitement around the treatment of impotence was raised by the American doctor John Brinkley (John R. Brinkley) in the 20-30s of the last century. In his radio broadcasts, he widely advertised the transplantation of goat sex glands and injections of mercury compound mercurochrome to restore male strength. When the Kansas Medical Commission revoked his medical license in 1930, and the Federal Radio Commission did not renew his broadcasting license, Brinkley did not calm down – he opened his clinic in Mexico, and broadcast advertising using a radio station across the border.
Modern interest in the search for erectile dysfunction therapy was largely aroused by the British physiologist Giles Brindley, who took off his pants in front of the affected representatives of the American Urological Association and demonstrated his penis in a state of erection after an intracavernous injection of the vasodilator drug phentolamine.
The richer, the less happyCurrently, there are many methods for the treatment of erectile dysfunction.
Anatomical defects that prevent the occurrence of a normal erection are eliminated by surgeons. They also help patients in the most hopeless cases by implanting inflatable or rigid implants into the penis, which, although they do not return a normal erection, allow sexual intercourse. In case of hormonal disorders, substitution therapy is prescribed.
Functional disorders of erection are treated with medications. The most famous and effective of them are phosphodiesterase inhibitors of the 5th type, relaxing the smooth muscles of the arteries of the penis and increasing blood flow to it. These are sildenafil, vardenafil and tadalafil (trade names, respectively, "Viagra", "Levitra" and "Cialis"). However, for all their advantages, these drugs still do not help everyone (according to a study conducted in 1999 at the American Johns Hopkins University, sildenafil is effective in 65% of patients, and in severe ED – in 41%). In addition, they require administration immediately before sexual intercourse, have side effects (including such serious ones as arrhythmias, heart attack and stroke) and have contraindications (for example, hypotension, impaired liver and kidney function, simultaneous administration with nitrates).
Other pharmacological drugs are even less effective (for example, yohimbine) or inconvenient to use (for example, alprostadil needs to be injected into cavernous bodies). In addition, all these remedies have only a symptomatic effect, without affecting the causes of the disease.
All this forces researchers to look for new, more advanced drugs. Thus, drugs with a new mechanism of action are currently undergoing clinical trials, for example, libido-boosting drugs by stimulating the brain's melanocortin receptors bremelanotide and melanotan II.
And we will go the other wayThe aforementioned researchers from the Albert Einstein College of Medicine decided to try a fundamentally new approach to the treatment of erectile dysfunction, based on an innovative method of gene therapy.
The starting point in their work was the discovery of the role of the Maxi-K protein in the occurrence of an erection (this role is most fully shown in a study conducted in 2002 by scientists from the same college together with colleagues from the New York Institute of Smooth Muscle Biology). This protein forms calcium-dependent potassium channels in the cell membranes, known as Maxi-K, BK or slo1 channels, which regulate the excitability of nerve cells and the tone of smooth muscles (including the arteries of the penis).
American researchers decided to conduct an experiment on the treatment of erectile dysfunction by introducing additional copies of genes encoding this protein into the cavernous bodies of patients. The most obvious solution was to use the gene therapy technique developed in the 1970s and improved in the following decades. It consists in the fact that the necessary gene is embedded in the DNA of the so–called viral vector - a virus from whose genome the genes responsible for the disease caused by this virus are removed. The virus is embedded in the DNA of human cells, adding the desired gene to it.
But, as previous studies in the field of gene therapy have shown, the use of the viral vector is associated with certain immunological and other complications. Therefore, American scientists used deproteinized DNA, a form of DNA closed in a ring and not bound to proteins. It is not embedded in the genome of human cells, however, the synthesis of the desired protein takes place on its matrix.
In accordance with the principles of medical research, the first series of experiments was performed on male laboratory monkeys Macacus cynomolgus. Stimulation of erectile function and sexual behavior was obvious in the absence of visible side effects, and scientists began studies on 11 volunteers aged 42 to 80 years, which also showed an undoubted effect for six months from the moment of injection in those who received a dose of genes from 5,000 to 7,500 micrograms.
After that, the volunteers remained under observation for two years. None of them had any side effects. In addition, no injected genes were found in the volunteers' sperm, which excludes their transfer to partners.
According to the head of the study, Professor Arnold Melman, such encouraging results can revolutionize the treatment of erectile dysfunction. Indeed, a technique that requires injections every six months and does not have a side effect looks more than attractive. In addition, it turned out that the introduction of an insufficient number of Maxi-K protein genes for the full effect increases the effectiveness of Viagra-type drugs, i.e. it shows synergy with them.
Whether the technique will become a real breakthrough and hope for those who are dissatisfied with their masculine strength, the further stages of the study will show. And while they are passing, there is still time for a discussion about the ethical side of gene therapy. With the appearance of the first works in this direction, it was raised by supporters of the religious idea of the creation of man by God in his own image. In their opinion, actions on the genetic apparatus are an unacceptable distortion and blasphemous interference in the divine creation. Time will tell what will overcome – religious feeling or the need for masculine strength.
Portal "Eternal youth" www.vechnayamolodost.ru23.05.2008