Scientists have developed an injectable drug that blocks 艾滋病毒 from entering cells. They say the new drug potentially offers long-lasting protection from the infection with fewer side effects. 这种药物, 在非人类灵长类动物身上测试过的, could eventually replace or supplement components of combination drug "cocktail" therapies currently used to prevent or treat the virus.
大发娱乐 scientists led the study in collaboration with researchers from the National Institute of Allergy and Infectious Diseases (NIAID), 贝斯以色列女执事医疗中心 以及Navigen公司.
"This is an exciting new 艾滋病毒 therapeutic option for both prevention and treatment, 具有独特的作用机制 compared to other approved drugs,” 迈克尔年代. 凯,M.D. Ph.D., a senior author of the study and a U of U Health professor of biochemistry. "It has great potential to help patients who suffer from drug resistance as well as those who would benefit from a longer-acting, 可注射的抗艾滋病毒药物鸡尾酒."
这项研究发表在 Proceedings of the National Academy of Sciences (PNAS).
到2019年，大约有1.7 million people worldwide were newly infected with 艾滋病毒, according to the World Health Organization. More than 38 million people are currently living with the infection. 抗逆转录病毒联合治疗（cART）, 所谓的“毒品鸡尾酒”," has dramatically improved survival and quality of life for such patients, 但它也很昂贵, 通常有严重的副作用, 并要求患者每天服药. 除了, 因为艾滋病毒经常变异, 耐药性是一个持续的挑战, 凯说, so researchers are always seeking new drugs with novel mechanisms of action to produce more robust combination therapies.
"This is an exciting new 艾滋病毒 therapeutic option for both prevention and treatment, 具有独特的作用机制."
在这项新研究中, the researchers tested a unique drug called CPT31, based on a D-peptide that targets a critical pocket on 艾滋病毒's fusion machinery that rarely mutates. D-peptides are mirror images of naturally occurring peptides. 想象一下，想想右手和左手. The building blocks and overall structure of natural peptides are analogous to our left hand versus our right hand for D-peptides.
Because of that, CPT31 and other D-peptides are not degraded in the body. 因此, 它们比天然肽持续时间长得多, making them especially suitable for a long-acting injectable formulation.
“除了它们在体内的耐用性, D-peptides are largely ignored by the immune system, preventing immune reactions that are a side effect often seen with traditional peptide and protein drugs,布雷特·韦尔奇说。, a co-author of the study and senior director of technology and strategy at Navigen, 公司., the Salt Lake City company that co-developed CPT31 and is managing clinical trials. 作为一种d肽, our hope is that CPT31 will provide extended viral suppression with a lower dose and reduced side effects."
看看CPT31是否能预防艾滋病毒感染, 凯 and colleagues first injected the drug into healthy macaque monkeys starting several days prior to exposure to a hybrid simian-human form of 艾滋病毒 called S艾滋病毒. The monkeys were completely protected from this very high S艾滋病毒 exposure, much higher than what humans typically encounter, 而且从未出现感染的迹象. 随后, the scientists identified the minimum dose of CPT31 needed to confer complete protection, information that will help inform clinical trials.
"We think this drug could be used by itself to prevent 艾滋病毒 infection because initial 艾滋病毒 exposure typically involves a relatively small amount of virus,凯说. "This study showed that the vast majority of circulating 艾滋病毒 strains from around the world are potently blocked by CPT31."
But what about later stages of the disease when there are billions of copies of the virus circulating in the body?
为了找出答案, the researchers gave CPT31 to monkeys with untreated S艾滋病毒 infections and high viral loads. 在30天的过程中, the drug significantly lowered the presence of S艾滋病毒 in their bloodstreams. 然而, virus levels rebound in two to three weeks due to drug resistance, as typically observed when treating established infections with a single drug.
"Such a simplified ‘maintenance therapy' could present patients with a new option for viral control that is more cost-effective, 方便携带, 而且副作用更少,凯说.
与临床试验同时进行, Navigen is developing a long-acting injectable formulation of CPT31 with the goal of only requiring injection of the drug once every three months.
"长效 injectable formulations appear to be greatly preferred by both patients and physicians compared to current daily drug regimens that can be challenging to maintain,韦尔奇说. “另外, the steady therapeutic drug levels provided by such a formulation would reduce the risk of drug resistance caused by missed daily pills, 同时减少副作用."
即将进行的人体试验, 定于今年晚些时候举行, will help determine whether CPT31 is safe and effective in humans. 凯说 that the full course of human clinical trials and subsequent FDA approval could take several years.
####
除了博士. 凯, other U of U Health researchers involved in this study titled, "Prevention and Treatment of S艾滋病毒AD8 in Rhesus Macaques by a Potent D-peptide 艾滋病毒 Early Inhibitor,我是J。.N. 弗朗西斯和A.R. 史密斯. 其他研究人员包括Y. Nishimura O. 多瑙河,E. Jesteadt R. Sadjadpour和M.A. Martin of the National Institute of Allergy and Infectious Disease (NIAID); and M.S. Seaman of 贝斯以色列女执事医疗中心. 这项研究是由 美国国立卫生研究院 （NIAID）和 Bill and Melinda Gates Foundation Collaboration for 艾滋病 Vaccine Discovery. Drs. 凯和韦尔奇持有Navigen的股权.