March 5, 2024

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New breakthrough in male contraceptives: Effect in 2 hours

New breakthrough in male contraceptives: Effect in 2 hours



 

New breakthrough in male contraceptives: Effect in 2 hours.

A new breakthrough in male contraceptives: it takes effect quickly in 2 hours, the contraceptive efficiency is 100%, and it can return to normal the next day.

 

According to statistics, on a global scale, the unwanted pregnancy rate is as high as 50%. Of the contraceptive methods currently available, they are primarily aimed at women, with few contraceptive/birth control options available to men other than condoms and vasectomy .

But condoms are disposable and prone to failure. And vasectomy, although it can sometimes be reversed, is expensive and not necessarily successful, so it can almost be considered a permanent method of sterilization.

 

Scientists have been working for decades to develop an effective male contraceptive, but so far have been unsuccessful.

The male contraceptives currently undergoing clinical trials are basically hormonal drugs.

These hormonal male contraceptives are effective against the male hormone testosterone, but they can cause side effects such as weight gain, depression, and increased LDL cholesterol levels.

 

On February 14, 2023, researchers from Weill Cornell Medical College published a research paper entitled: On-demand male contraception via acute inhibition of soluble adenylyl cyclase in the journal Nature Communications .

 

The study developed a soluble adenylyl cyclase (sAC) inhibitor, and mouse experiments showed that the contraceptive efficiency was as high as 100% within 2 hours after administration , and after 24 hours, fertility would return to normal levels, No negative health effects were found after continuous medication for 6 weeks.

This study brings new progress to the development of male contraceptive drugs.

 


New breakthrough in male contraceptives: Effect in 2 hours


Mature mammalian spermatozoa are stored in a dormant state in the caudate epididymis where bicarbonate is maintained at ≤5 mM. After ejaculation, mixing with semen exposes sperm to bicarbonate concentration levels of approximately 25 mM, thereby modulating the activity of soluble adenylate cyclase (sAC) .

This sAC-dependent increase in cyclic adenosine monophosphate ( cAMP ) is the initial signaling event to activate sperm motility and capacitation, and is a prerequisite for sperm to acquire fertilization capacity.

Male mice with sAC knockouts exhibited infertility, while males with homozygous mutations in the sAC gene were also infertile.

 

Sperm must swim a certain distance to meet the egg and complete the fertilization process, and if this swimming ability is lost, the fertilization process cannot be completed.

The research team has previously developed an inhibitor of soluble adenylyl cyclase (sAC) , which can specifically block sAC, prevent sperm motility, and achieve contraception in vitro or in mice .

 

In this latest study, the research team developed an optimized TDI-11861 based on the previously developed soluble adenylyl cyclase (sAC) inhibitor TDI-10229 .

TDI-11861 is approximately 50 times more potent than TDI-10229 in inhibiting sAC proteins in vitro , and remains on sAC proteins for approximately 200 times longer.

 

The TDI-11861 inhibitor has drug-like properties suitable for in vivo use in animal models, has reduced cross-reactivity with other mammalian adenylyl cyclases, and is not significantly cytotoxic.

 

New breakthrough in male contraceptives: Effect in 2 hours

 

Next, the research team performed a series of proof-of-concept experiments using groups of mice that supported the contraceptive efficacy of sAC inhibitors.

Specifically, under normal mating conditions, the contraceptive effect of TDI-11861 can be achieved within a few hours after administration, and the contraceptive effect is as high as 100% after 2 hours of administration , and 91% after 3 hours.

And by 24 hours, the fertility of the male mice returned to normal levels . In addition, no negative health effects were found after continuous administration for 6 weeks.

 

New breakthrough in male contraceptives: Effect in 2 hours

 

 

Although most of the drugs in this study were administered by injection, oral administration also reduced sperm motility in male mice to the same level, the research team said.

 

It should be noted that men who are infertile because of homozygous mutations in the sAC gene have a higher risk of kidney stones, but only if sAC is blocked for a long time (months to years) .

And sAC inhibitors only exist in the body for a short time, so there is not enough time to cause kidney stone risk. Long-term administration in mouse experiments also showed no tendency for kidney stones.

 

The research team said that this study proved that an on-demand contraceptive pill for men is feasible .

The research team also said that the sAC inhibitor will be further improved, hoping to develop improvements that can enter human clinical trials in the next 2-3 years version of the sAC inhibitor.

 

 

 

 

Paper link :
https://www.nature.com/articles/s41467-021-21517-5
https://www.nature.com/articles/s41467-023-36119-6

New breakthrough in male contraceptives: Effect in 2 hours

(source:internet, reference only)


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