男性用経口避妊薬、マウス実験で９９％の効果 米研究

【ＡＦＰ＝時事】マウス実験で９９％の効果があり、目立った副作用のない非ホルモン性の男性用経口避妊薬（ピル）を開発したと、米ミネソタ大学の研究チームが２３日、発表した。年内にヒト臨床試験に入る見通しだ。（写真は資料写真）
　この研究成果は、米国化学会春季年会で発表される。避妊における男性側の選択肢と責任の拡大に向けた重要な一歩となる。
　女性用ピルが初めて認可されたのは１９６０年代。今回発表を行う大学院生のアブドラ・アル・ノーマン氏によると、複数の研究で、男性に避妊の責任を分担することへの関心があることは分かっていた。
　しかし、これまでは効果的な選択肢がコンドームか精管切除しかなく、後者は高価なうえ成功するとは限らなかった。
　女性用ピルは、女性ホルモンの分泌をコントロールすることで月経周期を調節する。男性用ピルの開発でも長年、男性ホルモンのテストステロンに的を絞って研究が進められてきたが、体重増加やうつ病、心臓病リスクを高めるＬＤＬ（悪玉）コレステロール値の上昇といった副作用が問題となっていた。
　非ホルモン性ピルの開発にあたり、ノーマン氏は「レチノイン酸受容体アルファ（ＲＡＲα）」というたんぱく質に着目。所属研究室のグンダ・ゲオルク教授と共に、コンピューター・モデルを用いてＲＡＲαの作用をピンポイントで阻害する化合物「ＹＣＴ５２９」を開発した。
　ＲＡＲαは体内でビタミンＡ代謝産物のレチノイン酸に作用し、細胞の成長、精子の形成、胚の発生に重要な役割を果たす。ＲＡＲαを作り出す遺伝子のないマウスは不妊になることが実験で分かっている。
　「ＹＣＴ５２９」を４週間経口投与したマウスは精子数が劇的に減少し、交配試験で９９％の妊娠予防効果を示した。マウスの体重、食欲、全体的な活動に明らかな悪影響は認められなかった。投与中止から４～６週間後にマウスの生殖能力は戻った。
　研究チームは米国立衛生研究所（ＮＩＨ）と男性用避妊薬イニシアチブ（ＭＣＩ）から資金提供を受けている。ゲオルク教授によれば、スタートアップ企業のユアチョイス・セラピューティクスと協力して今年後半にヒト臨床試験を開始する予定で、５年以内の市場投入を目指している。【翻訳編集ＡＦＰＢＢＮｅｗｓ】
〔ＡＦＰ＝時事〕（2022/03/24-16:28）

A team of scientists said Wednesday they had developed a male oral contraceptive that was 99 percent effective in mice and didn't cause observable side effects, with the drug expected to enter human trials by the end of this year.
The findings will be presented at the American Chemical Society's spring meeting, and mark a key step towards expanding birth control options -- as well as responsibilities -- for men.
Ever since the female birth control pill was first approved in the 1960s, researchers have been interested in a male equivalent, Md Abdullah Al Noman, a graduate student at the University of Minnesota who will present the work, told AFP.
Multiple studies showed that men are interested in sharing the responsibility of birth control with their partners, he said -- but until now, there have been only two effective options available: condoms or vasectomies.
Vasectomy reversal surgery is expensive and not always successful.
The female pill uses hormones to disrupt the menstrual cycle, and historic efforts to develop a male equivalent targeted the male sex hormone testosterone.
The problem with this approach, however, was that it caused side effects such as weight gain, depression and increased levels of a cholesterol known as low-density lipoprotein, which increases heart disease risks.
The female pill also carries side effects, including blood-clotting risks -- but since women face becoming pregnant in the absence of contraception, the risk calculation differs.
- Non-hormonal -
To develop a non-hormonal drug, Noman, who works in the lab of Professor Gunda Georg, targeted a protein called retinoic acid receptor (RAR) alpha.
Inside the body, vitamin A is converted into different forms, including retinoic acid, which plays important roles in cell growth, sperm formation, and embryo development.
Retinoic acid needs to interact with RAR-alpha to perform these functions, and lab experiments have shown mice without the gene that creates RAR-alpha are sterile.
For their work, Noman and Georg developed a compound that blocks the action of RAR-alpha. They identified the best molecular structure with the help of a computer model.
If we know what the keyhole looks like, then we can make a better key -- that's where the computational model comes in, said Noman.
Their chemical, known as YCT529, was also designed to interact specifically with RAR-alpha, and not two other related receptors RAR-beta and RAR-gamma, in order to minimize potential side effects.
- Five years to market? -
When administered orally to male mice for four weeks, YCT529 drastically reduced sperm counts and was 99 percent effective in preventing pregnancy in a mating trial.
The researchers monitored weight, appetite and overall activity, finding no apparent adverse impacts, although mice of course can't report side effects like headaches or mood changes.
Four to six weeks after they were taken off the drug, the mice could once more sire pups.
The team, which received funding from the National Institutes of Health and the Male Contraceptive Initiative, is working with a company called YourChoice Therapeutics to start human trials by the third or fourth quarter of 2022, said Georg.
I'm optimistic this will move forward quickly, she said, envisaging a possible timeline to market in five years or under.
There is no guarantee that it will work...but I would really be surprised if we didn't see an effect in humans as well, she added.
A persistent question about future male contraceptive pills has been whether women will trust men to use them.
But surveys have shown that most women would in fact have faith in their partners, and significant numbers of men have indicated they would be open to the medication.
Male contraceptives will add to the method mix, providing new options that allow men and women to contribute in whatever way they deem appropriate to contraceptive use, argues the nonprofit Male Contraceptive Initiative, which engages in fundraising and advocacy.