Latest news with #anti-NMDA
Business Wire
17-06-2025
- Business
- Business Wire
Arialys Therapeutics Publishes Preclinical Data in Nature Communications Supporting ART5803 as a First-in-Class Precision Therapeutic for Anti-NMDA Receptor Autoimmune Neuropsychiatric Disease
LA JOLLA, Calif.--(BUSINESS WIRE)-- Arialys Therapeutics, a clinical-stage biotechnology company pioneering new precision medicines for autoimmune neuropsychiatric diseases, today announced the publication of preclinical data in Nature Communications demonstrating that its lead drug candidate, ART5803, effectively blocks the underlying disease mechanism in anti-NMDA receptor encephalitis (ANRE) and rapidly reverses behavioral symptoms in a non-human primate model. The findings support the continued clinical development of ART5803 as a first-in-class, targeted therapeutic. The company is currently completing Phase 1 safety studies for ART5803 and plans Phase 2 evaluation in anti-NMDA receptor encephalitis (ANRE) and autoimmune psychosis patients in the second half of 2025. 'This study underscores the promise of ART5803 to directly address neuropsychiatric disease caused by anti-NMDA receptor-targeting pathogenic antibodies,' said Peter Flynn, Ph.D. President and CEO of Arialys Therapeutics. Share 'This study underscores the promise of ART5803 to directly address neuropsychiatric disease caused by anti-NMDA receptor-targeting pathogenic antibodies,' said Peter Flynn, Ph.D. President and CEO of Arialys Therapeutics. 'Despite our understanding of the disease mechanism and its severity, ANRE lacks an approved therapy. Further, there is a growing body of data identifying significant levels of anti-NMDA receptor autoantibodies in subpopulations of patients diagnosed with diseases that result in psychosis and dementia.' 'These data provide compelling evidence that ART5803 can directly block the pathogenic effect of autoantibodies that target the NMDA receptor, resulting in a rapid resolution of symptoms,' said Mitsuyuki (Mickey) Matsumoto, Ph.D., Chief Scientific Officer of Arialys Therapeutics and senior author of the paper. 'Our detailed structural and functional analyses confirm that ART5803 precisely inhibits NMDA receptor internalization induced by the pathogenic autoantibodies, while preserving normal receptor function. In addition, our discovery of a potential molecular mimicry mechanism for anti-NMDA receptor autoantibody generation broadens the understanding of disease initiation and may inform future indication expansion for ART5803.' Anti-NMDA receptor encephalitis (ANRE) is a rare, potentially lethal, poorly managed, and often misdiagnosed neurological disease. ANRE is caused by pathogenic autoantibodies that bind to and crosslink NMDA receptors in the brain, leading to receptor internalization and synaptic dysfunction. The result is a range of debilitating neuropsychiatric symptoms including psychiatric and behavioral alterations, cognitive decline, seizures, coma, and diminished autonomic function. A significant percentage of ANRE patients are pediatric, where NMDA receptor-specific autoantibodies can also result in neurological development deficits. There are no approved therapies for this disease, and current treatments rely on broadly immunosuppressive therapies, which are associated with delayed efficacy and significant side effects. Recent findings have also identified anti-NMDA receptor autoantibodies in other neurological and psychiatric diseases such as schizophrenia, depression, bipolar disorder, and dementia. Arialys is planning clinical assessment of ART5803 in anti-NMDA receptor autoantibody-positive psychosis patients. The company is also currently testing patient samples using a proprietary high-throughput screen for autoantibodies to identify enriched disease indications and subpopulations for future clinical development. ART5803 is a humanized, monovalent IgG1 antibody engineered to selectively bind the GluN1 subunit of the NMDA receptor without disrupting receptor function or causing internalization. In this study, ART5803 demonstrated the ability to potently block NMDA receptor internalization in cellular and neuronal models and reversed both molecular and behavioral hallmarks of disease in a novel marmoset model of ANRE. Notably, ART5803 exhibited rapid onset of action and was well tolerated in vivo. The publication also includes a detailed characterization of ART5803's binding epitope, its mechanism of action, and population pharmacokinetic modeling supporting the feasibility of systemic administration in patients. In addition to demonstrating the therapeutic potential of ART5803, the paper revealed a potential link between infections—specifically Toxoplasma gondii and certain bacterial pathogens—and the generation of pathogenic anti-NMDA receptor autoantibodies. Epitope mapping analysis identified regions of potential molecular mimicry between microbial proteins and the GluN1 subunit of the NMDA receptor, suggesting that infections could serve as environmental triggers for disease initiation. Notably, toxoplasmosis and bacterial infections are well-established risk factors for a range of neuropsychiatric conditions. These findings not only suggest a basis for disease pathogenesis but also support broader therapeutic opportunities for ART5803 across autoimmune neuropsychiatric disorders. ART5803 is currently being evaluated in a Phase 1 clinical trial in healthy volunteers. In February 2025, Arialys announced completion of all single ascending dose (SAD) cohorts and initiation of multiple ascending dose (MAD) cohorts. The company expects to share initial clinical data in the second half of 2025 and initiate Phase 2 proof-of-concept studies. The publication was completed in collaboration with researchers from Astellas Pharma Inc., University of California, Davis, Kitasato University School of Medicine, and Vanadro LLC. About Arialys Therapeutics Arialys was founded by investors Avalon Bioventures, Catalys Pacific and MPM to meaningfully expand the treatment possibilities for neuropsychiatric disorders driven by autoimmune disease. Using a combination of highly sensitive autoantibody detection, patient sampling and receptor structural biology, Arialys has developed a first-in-class precision therapy to specifically block pathogenic autoantibodies in the brain. Arialys is headquartered in La Jolla, California. For more information, visit
San Francisco Chronicle
22-04-2025
- Entertainment
- San Francisco Chronicle
Susannah Cahalan's ‘The Acid Queen' reclaims the legacy of a psychedelic pioneer
Author Susannah Cahalan is admittedly obsessed with the human mind. That intense interest developed after battling a life-threatening case of anti-NMDA receptor encephalitis at the age of 24. Documented in Cahalan's bestselling 2012 memoir, 'Brain on Fire: My Month of Madness,' her harrowing experience was adapted into a film for Netflix in 2016. It also left the writer insatiably intrigued with altered states of consciousness and their profound, at times life-altering, effects. More Information The Acid Queen The Psychedelic Life and Counterculture Rebellion of Rosemary Woodruff Leary By Susannah Cahalan (Viking; 384 pages; $32) Susannah Cahalan in conversation with Meg Josephson: 6 p.m. Wednesday, April 30. Free. 51 Book Passage, Tamal Vista Blvd., Corte Madera. 415-927-0960. Cahalan's latest book returns to this theme by offering the first comprehensive biography of Rosemary Woodruff Leary, a pioneering psychonaut who helped to reshape the minds of an entire generation. In 'The Acid Queen: The Psychedelic Life and Counterculture Rebellion of Rosemary Woodruff Leary,' Cahalan offers a full portrait of the third wife of the pro-LSD psychologist Timothy Leary by providing rich details of her life beyond the exploits of her infamous spouse. Cahalan traces her subject's story from her birth in St. Louis, Mo. as Rosemary Sarah Woodruff, to her first taste of the counterculture as wife of jazz accordionist Mat Matthews. Already twice divorced yet barely old enough to legally drink, her introduction to Leary in 1965 in Millbrook, N.Y., united two figures who together would help usher LSD into the American lexicon. Among her many interviewees, Leary's son, Jack, from a previous marriage, told Cahalan that he 'thought more of (Rosemary) as my mother than Timothy as my father,' according to the book. He went on to praise Woodruff Leary as 'about the sanest and kindest of the hundreds of people' who came through his father's estate-turned-commune in Millbrook, where the couple spent their heyday ingesting copious amounts of LSD. Following Leary's arrest for marijuana possession at the U.S.-Mexico border, Woodruff Leary spent 30 days in jail for refusing to testify on her husband's behalf before subsequently disguising herself to play a key role in his daring jail break in 1970. Woodruff Leary remained on the lam, living under assumed identities for large swathes of the next two decades before finally coming back above ground in her final years. Though both figures would take other lovers, the pair's devotion to one another, if imperfect, always remained at least partially intact for the duration of their lives (Leary died at 75 in Beverly Hills in 1997; Woodruff Leary died at 66 in Aptos in 2002). 'The Acid Queen' includes many never-before-published details of Woodruff Leary's life on Cape Cod under the assumed name Sarah Woodruff, and marks yet another compelling entry in the growing body of work reclaiming the stories of women unfairly relegated to the footnotes of history. Arriving just weeks after the release of David Sheff's new biography of Yoko Ono, Cahalan acknowledged that the moment feels right to be publishing books detailing the full, singular lives of women like Ono and Woodruff Leary, who both notably appear in the1969 'Give Peace a Chance' video filmed during John Lennon and Ono's anti-war 'bed-in' protest. 'The boomer narrative of peace and love doesn't focus a lot on women,' Cahalan told the Chronicle. 'When I went to look at serious work done on the women of that era, if you're not talking about Janice Joplin or Stevie Nicks — just like the everyday hippie woman, for lack of a better word — there's very little scholarship on them. They were not taken seriously at all, and I feel they haven't been afforded the place in the culture that they deserve.' Cahalan described a moment of serendipity that led her to Rosemary Woodruff Leary's story. After visiting the Timothy Leary archives at the New York Public Library in search of inspiration for her third book, the author recalls browsing a Brooklyn boutique when she spotted a long maxi dress covered in black poppies. She didn't buy the piece from Swedish designer Carin Rodebjer's 2020 resort collection, but upon further research Cahalan learned its aesthetic was inspired by the 'free intellect and relaxed style' of Rosemary Woodruff Leary. 'It was like something was conspiring in this very self-referential way to compel me to explore this deeper,' she shared. Ahead of an appearance at Book Passage's Corte Madera store on Wednesday, April 30, Cahalan spoke with the Chronicle by Zoom from her New York City apartment about her research process and the critical role the Bay Area played in Woodruff Leary's life. This conversation has been edited for length and clarity. Q: Was there a specific moment in your research where you realized Rosemary Woodruff Leary's life was a book-worthy story? A: The first thing was realizing how big her life was before Leary. She was a stewardess. She hung out with the Kerouacs of the world and the jazz musicians of New York City. She was a beatnik chick, divorced twice before she had even met (Timothy Leary). Leary wasn't even the most fascinating thing about her. The thing that sold it for me was the undercover life she lived later on. It wasn't even helping Leary with his jailbreak; it was this life she spent living as Sarah Woodruff under an assumed name in Cape Cod. That was never written about beyond a brief mention. That was my signal that this was a book. Q: Is it fair to assume you tracked down a few colorful characters who knew Timothy and Rosemary to help you flesh out the story? A: Yes, I talked to people from various stages of her life. (One of the) most important people was her brother, Gary Woodruff. He gave me access to archives that aren't in the New York Public Library. His sister was very much a mystery to him, and I think reading the book was somewhat revelatory for him as well. Her lover, John Schewel, is who she was underground with during her time in South America and Europe and that was never known before. John had never spoken about it before, so that was amazing. I found people from the pre-Leary New York days, like David Amram. I think he's 99 now and he's an amazing jazz musician who knew her. And then there were the Cape Cod people. To some people, she was Sarah the whole time, so they had a fun time hearing about her life before that time. Q: It seems like the Bay Area, and Northern California at large, played a pretty key role in Rosemary's life. A: Golden Gate Park is where Timothy Leary told the world to ' turn on, tune in, drop out.' It has a critical place in the saga of Rosemary and obviously in Timothy's saga as well. Interestingly, she was not present when he said that, because she was tired of all the fame. Once they got to California, that's when Timothy hit a new notoriety and apex in his fame. They were also with the Grateful Dead at various points, and they rubbed shoulders with all these interesting Hollywood types too. For Rosemary, when they went to California, it was at the height of her powers as a mediagenic person. It was where she became the 'Acid Queen,' as Allen Ginsberg called her. She was deeply intertwined with the counterculture press and got quoted constantly. When Leary was put in jail, she was the one facing the cameras and advocating on behalf of freedom of use for psychedelic drugs. She was advocating for his release. She was raising money for his trial, then his appeal. She really came into her own in the Bay Area. Q: You point out early in the book that one may never have noticed Rosemary's presence in the front left of the famous 'Give Peace a Chance' bed-in photo of John Lennon, Yoko Ono and Timothy Leary. Exactly. And if you extrapolate from there, this whole story is a question of where the camera should be, right? It was on Leary, and she was in the shots, and she augmented them because she was so beautiful. But it was so satisfying to shift the camera and focus it on her. It really changed the way I viewed everything about the whole story, and it also gave me an opportunity to focus on someone who's not typically the subject of a book or a biography. At the end of the book, I talk about how Rosemary was a mythmaker, and how she spent her life creating her own myth and this idea that we only can get so close to the truth. It's something that I see as a through line in all my books. I think a lot of us are seekers and looking for meaning, especially these days, and Rosemary was someone who saw that as a worthwhile pursuit, as something that can and should be taken seriously. She saw it as something valuable and it was so fun for me to explore that idea through her. It's something that I believe we all think about and I'm not sure if she ever found it.
