Treating Schizophrenia with Muscarinic Antipsychotics

Treating Schizophrenia with Muscarinic Antipsychotics | Steve Paul

Рет қаралды 8,798

9 ай бұрын

Steve Paul, MD, Chief Scientific Officer & President of Research and Development at Karuna Therapeutics, gives the keynote presentation, "Muscarinic Antipsychotics: A Potential New Generation of Medicine for Treating Schizophrenia," at the Science & Innovation Symposium, sponsored by Rogers Behavioral Health, as part of One Mind's 29th Music Festival for Brain Health, held on September 9, 2023 at the Staglin Family Vineyard.
Watch all the 2023 Science & Innovation Symposium presentations here in the full playlist: • One Mind's 2023 Scienc...
Schizophrenia remains a challenging disease to treat effectively with current antipsychotic medications due to their limited efﬁcacy across the entire spectrum of core symptoms as well as their often burdensome side-effect proﬁles and poor tolerability. An unmet need remains for novel, mechanistically unique, and better tolerated therapeutic agents for treating schizophrenia, especially those that treat not only positive symptoms but also the negative and cognitive symptoms of the disease. Almost 25 years ago, the muscarinic acetylcholine receptor (mAChR) agonist xanomeline was reported to reduce psychotic symptoms and improve cognition in patients with Alzheimer’s disease. The antipsychotic and procognitive properties of xanomeline were subsequently conﬁrmed in a small study of acutely psychotic patients with chronic schizophrenia. These unexpected clinical ﬁndings have prompted considerable efforts across academia and industry to target mAChRs as a new approach to potentially treat schizophrenia and other psychotic disorders. I will discuss recent advances in mAChR biology and pharmacology and the current understanding of the relative roles of the various mAChR subtypes, their downstream cellular effectors, and key neural circuits mediating the reduction in the core symptoms of schizophrenia in patients treated with xanomeline. I will also provide an update on the status of novel mAChR agonists currently in development for potential treatment of schizophrenia and other neuropsychiatric disorders.
STEVE PAUL - BIO
Steve Paul is the Chief Scientific Officer, President of Research and Development, and a member of the board of directors at Karuna Therapeutics. He most recently served as Chairman of the Board, President, and Chief Executive Officer from 2018 - 2022. He is an expert in central nervous system (CNS) drug discovery and development. Dr. Paul spent 17 years at Eli Lilly and Company (NYSE: LLY), during which time he held several key leadership roles, including Executive Vice President for Science and Technology and President of the Lilly Research Laboratories. At Lilly he was responsible for the company’s overall research and development efforts and helped to oversee the development of CNS drugs such as Zyprexa® and Cymbalta® as well as the development of xanomeline where its antipsychotic and procognitive properties were initially demonstrated.
Prior to Lilly, Dr. Paul spent 18 years at the National Institute of Health (NIH) and served as the Scientific Director of the National Institute of Mental Health (NIMH). Dr. Paul is a co-founder and board member of Sage Therapeutics (NASDAQ: SAGE) and a co-founder of Voyager Therapeutics (NASDAQ: VYGR) where he served as President, Chief Executive Officer. Dr. Paul is the former director of the Appel Alzheimer’s Disease Research Institute at Weill Cornell Medical College and is currently a Professor of Psychiatry and Neurology at Washington University of St. Louis School of Medicine.
ABOUT ONE MIND
One Mind is the leading brain health nonprofit committed to healing the lives of people impacted by brain illness and injury through global, collaborative action. One Mind catalyzes visionary change through science, business, and media to dismantle stigma and discrimination and transform the world’s mental health. One Mind accelerates collaborative research and advocacy to enable all individuals facing brain health challenges to build healthy, productive lives.
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#Schizophrenia #Science #MentalHealth #MentalIllness #SMI #OneMind #BrainHealthForAll

Пікірлер: 80

@sheila4933 9 ай бұрын

Thank you for this video. I have a family member who suffers from schizophrenia. So grateful that scientists and doctors are trying to find ways to relieve the suffering that people with this disease.

@lakshminandish5037 7 ай бұрын

Is that person had any birth related problem as you know like early birth or low birth weight or any......I too have schizophrenia reason may b low birth weight so asking

@dry509 5 ай бұрын

Same here. Anxiously awaiting any new development. Have you watched any of the Dr Chris Palmer videos where he investigates causes of the disease outside of the brain?

@patriciajump9511 7 ай бұрын

When I worked at a state hospital, and they first began to use Abilify, what I noted was that many patients became sociable. Now, Ability did not tamp down their hallucinations. In fact, the patients happily openly talked with their voices. What allowed them to be sociable was that they were not ashamed or embarrassed by their voices. Of course, these were patients whose voices were not hostile to them, did not upset them, and the voices were not command hallucinations. Still, the patients did not become well enough to be discharged. Their quality of life was improved, though.

@therealhotchocolatecompany3962 19 күн бұрын

On abilify all my positive symptoms stop.

@cjljianlang8240 19 күн бұрын

5:45 Symptoms 12:14 Negeative Cognitive Symptoms 16:00 Cognition 19:34 Cognitive Negeative Symptoms

@susansmith9462 Ай бұрын

My 23 year old son experienced his first episode of psychosis and subsequent diagnosis of schizophrenia 18 months ago with 3 hospitalizations and is presently on 6mg daily of risperidone and 1mg of Rexulti. He is no longer hearing voices but the weight gain,lethargy, and cognitive changes are painful for me to watch. I have read a little about KarXT and felt optimistic but recently his young psychiatrist told us he attended a conference and there was lots of discussion of KarXT and the takeaway was that it only shows some benefit for first time psychosis patients never treated with other antipsychotics and only as an adjunct to other antipsychotics. Needless to say I am a little confused from that and hope he is mistaken because I was hoping that it is improved in September and we could gradually transition him to KarXT with a lower dose of risperidone

@therealhotchocolatecompany3962 19 күн бұрын

Thats disappointing. I hope he's wronge.

@tomjones2348 7 ай бұрын

Each human has their own unique biochemistry. Some people require geometrically more of specific nutrients than other people. In my experience, schizophrenia is a symptom. In some cases, there can me multiple causative factors including environmental. I would encourage those with a family member dealing with this issue to read a few books: "Niacin- The Real story" by Abram Hoffer md. "The devil in the Milk" by Keith Woodford (regarding the bcm7 molecule), "Miller's review of critical vaccine studies "by Neil Z. Miller, "Thiamin deficiency disease Dysautonomia and high calorie malnutrition" by Derrick Lonsdale and Chandler Marrs, Anatomy of an Epidemic by Robert Whitaker, and Medication Madness by Peter Breggin.

@lindasantini5618 7 ай бұрын

How awesome that you've found Dr. Hoffer's work and orthomolecular medicine! I took my loved one to see Dr. Hoffer over on Vancouver Island many years ago. Unfortunately, his B-3 treatment wasn't effective. What worked was lowering my loved one's histamine level, according to Dr. Carl Pfeiffer's books. I have 3 videos here on YT at "Linda Van Zandt's Mental Health Recovery Channel" on the orthomolecular approach. What finally cured my loved one at a very deep level was homeopathy. He had Toxoplasmosis gondii. According to the NIH, one out of every five (!) cases of schizophrenia is actually an infection of T. gondii. They also say the herb, artemisinin, kills these protozoa. I gave my loved one the homeopathic form of artemisinin, among many other "remedies," (homeopathic medicines). The World Health Organization (WHO) says that homeopathy is the second most widely used system of medicine in the world. I can see why. --Linda, also author of "Goodbye, Quacks-Hello, Homeopathy!

@mikekaze7175 2 ай бұрын

Can u please explain a little. Have you found a cure/treatment? Please help! Btw I'm also seeing a doctor but i don't wanna take these medicines for life. Pls help!

@victoroncrypto 8 ай бұрын

Thank you for posting this video, I’m super excited for this new drug and hopefully they can bring it to the Australian market too in the near future.

@pamami1227 7 ай бұрын

As with all meds, they've started by saying the side effects are negligible. Only time will tell. Hope the prescribers will listen to the patients.

@gitashrigoswami3664 Ай бұрын

Very informative.

@DebbieMassey-ph1ok 7 ай бұрын

I hope this works,it's sad to see people that have to live there life like this. My son has this problem but hasn't taken anything bto help him, hopefully he can be convinced he needs to have help for this, thank you for caring because they are human beings that need to live a better life.

@lakshminandish5037 7 ай бұрын

I too have schizophrenia...Is he had any birth related problems.....like low birth weight or distress at birth......anybody else have this problem in your family

@DebbieMassey-ph1ok 7 ай бұрын

@@lakshminandish5037 not that I'm aware of.

@lakshminandish5037 7 ай бұрын

@@DebbieMassey-ph1ok because I was born with low birth weight.....thought that may b the reason From India where it is rare to find this disease

@lindasantini5618 7 ай бұрын

Debbie, if you want to actually cure a mental illness you have to know what's causing it. Conventional psychiatrists have no clue. They are only taught to match up symptoms to PATENTED, synthetic drugs so they can "manage" those symptoms until the patient eventually dies. Why? Because it's all about the profits, not curing anyone. When MY loved one became "incurably" mentally ill with "bipolar with psychosis," I used the "orthomolecular" approach to restore his mental health. It worked so well that I have 3 videos on this approach here on KZfaq at "Linda Van Zandt's Mental Health Recovery Channel." Orthomolecular treatment is easy to learn. I eventually used homeopathy to CURE my loved one, then wrote a book about it: "Goodbye, Quacks-Hello, Homeopathy!" The e-book will be coming out soon but for now, it's just a paperback. Conventional mental health care really is a racket. It isn't designed to cure anyone, just bring in the highest profits. Sadly, it's all perfectly legal because there is NO federal law that requires the APA to even try to cure anyone. Linda at Linsant 99 at gmail.

@originate2464 6 ай бұрын

Another problem with D2 blocking medications is that sometimes they cause akathesia, an always present feeling like you have to walk, but no amount of walking ever relieves it. It is constant discomfort. Other options that work on a different mechanism than what is currently available are needed

@nagarjunakallathur6270 8 ай бұрын

Great news.i need this medicine from India

@lakshminandish5037 7 ай бұрын

Hi sir I too have schizophrenia......from Mysore Karnataka

@nagarjunakallathur6270 7 ай бұрын

@@lakshminandish5037 Telugu or Tamil

@prashantsrivastava1333 6 ай бұрын

@@lakshminandish5037 Is medicine cured the disease

@shrinidhikulkarni479 Ай бұрын

Neuland Labs an Indian company worked with Karuna in scaling the required API. I know this is useless information. May be reach out to them and try your luck? Take care

@katherinepilgrim3461 14 күн бұрын

Please send this to Dr. Cathal Grant in Texas

@PolygoneNative 5 ай бұрын

Very interesting. Schizophrenia is often a debilitating condition for some. Anything that gives those living with it a better quality of life, sense of calm, balance and ability to participate in life more fully is a significant stride in the right direction.

@abdulhye5052 6 ай бұрын

Thanks for your video and get a valuable information about the the new drug for treating schizophrenia. When will get this drugs available?

@saradoun 4 ай бұрын

Ça donne de l'espoir pour les gens qui souffre de cette maladie, merci pour votre travail et bon courage pour vous et courage pour ceux qui souffrent 🙏👍

@pamami1227 7 ай бұрын

So brilliant of KZfaq to have this clip next to Joanna Moncrieff's "The Myth of the Chemic Cure"

@RynaxAlien 7 ай бұрын

When this drug comes to the market? Sleep medications for schizophrenia?

@PallabAdhikary-op1ox 6 ай бұрын

When it will available in India??

@nagarjunakallathur6270 6 ай бұрын

Same problem

@El-wc5hl 7 ай бұрын

Aminita Muscaria contains muscarinic acid.

@patrickm1666 25 күн бұрын

I have high hopes for this medication. Was hoping for ulotaront too

@ps-zt7tw 7 ай бұрын

How about collaborating with those truly interested in curing chronic Lyme disease (some have additional symptoms of 24/7 8/10 brain, hand, feet, bladder burning) the past 40+ years?

@SusanAzoulayF 2 ай бұрын

Will it be available in Mexico?

@SusanAzoulayF 2 ай бұрын

Anyone know what’s happening with this medicine? When will it be available?

@jeffvolpe4117 Ай бұрын

FDA will review in September (PDUFA). Hopeful commercialization and release in Fall 2024. Hope that helps.

@leighdencker 6 ай бұрын

What is the data on the Clozapine resistant people?

@lopchong7768 6 ай бұрын

I thank you as well. My son has schizophrenia which came on at the age of 22. He has all the side effects mentioned in your talk. Trump, when he was President, created “Right to Try”. Drugs that are still in the trial stage were given to patients who were going to die. Hence “Right to Try”. Do you think my son could get into your program or study? What’s he got to loose. He’s on so much anti-psychotics it saddens me. LMK

@maxaffe3195 4 ай бұрын

i think there are studies but i do not know where

@susansmith9462 Ай бұрын

@JerryFallwell-bt3py 8 ай бұрын

Teacher in Egypt there is an factoid an ancient city that was built in Abu Simbel Valley of The Kings where statue 100 ft carved into mountains in size. they wrote of themselves ;The Gods That Walked The Earth.

@Roberto11231 8 ай бұрын

So KarXT is good against negative symptoms?

@nemo3874 7 ай бұрын

nope, for negative symptoms it's just 1.8 points which is about same as olanzapine

@mapodev 5 ай бұрын

@@nemo3874 look at 19:02 it clearly states that negative symptons go down almost 4 points

@maxaffe3195 4 ай бұрын

@@nemo3874 really man? and they said it helps?????????

@winstonblue457 6 ай бұрын

How much time it gonna Take to come in europe

@maxaffe3195 4 ай бұрын

you can get international delivery. your doctor can write a prescription and your pharmacist needs to order.

@maxaffe3195 2 ай бұрын

and then you maybe need to agree and sign something like agreement to off label use so your doctor is on the safe side

@berserksArea52 3 ай бұрын

I suffer from schizophrenia and they offered me kar xt through a study today and trying to sed if i should take it been disabled since i was 18-19 it strikes in early adulthood late adosclenct age. Let me know how this drug works for yall please

@SangamesOfficial 2 ай бұрын

How did it work for u

@Faye-el1bz 5 ай бұрын

It can also be triggered by consistent abuse .I have been viciously abused for twenty years by a group of psychics who isolated me for my family who wanted access to all of my money and my neighbour was bought off to harrass me out of my home they were successful Isolation is a toxic state to live in so is constant stalking by unethical obsessed men Shout out to the psychics who attended Glenroy primary school who fancy themselves as having family worthy of becoming ASIO agents

@jeanpaultongeren125 6 ай бұрын

kARxt GONNA BE BIG.

@Roberto11231 6 ай бұрын

It is not good against negative symptoms. It will be the same as traditional antipsychotics.

@mapodev 5 ай бұрын

@@Roberto11231 How do you know that? He said, it is also good for negative symptoms

@Roberto11231 5 ай бұрын

@@mapodev In the essay responses, the score for negative symptoms was 3.2. While with placebo it was 1.8

@mapodev 5 ай бұрын

@@Roberto11231 why does He say then, that it handles all three kinds of Symptoms?

@maxaffe3195 4 ай бұрын

@@Roberto11231 but what about the PANSS he mentioned at minute 18

@willcoll8789 8 ай бұрын

Why not just cut to the chase and deal with the underlying metabolic disorder, rather than just masking symptoms?

@Unboxedwhimsey 7 ай бұрын

Exactly

@mikekaze7175 2 ай бұрын

Can u please explain a little. Have you found a cure/treatment? Please help! Btw I'm also seeing a doctor but i don't wanna take these medicines for life.

@mikekaze7175 2 ай бұрын

Please explain more , help.

@this_lifenow 2 ай бұрын

Enlighten us on what you mean please.

@willcoll8789 2 ай бұрын

@@this_lifenow The emerging new understanding of schizophrenia and other mental disorders as metabolically driven, in terms of brain metabolism and brain energy deficits. This is all explained on the Metabolic Mind channel, and the work of Chris Palmer, MD, Georgia Ede, MD, and others who are having success treating with diet & nutrition-based intervention.

@samgee7999 4 ай бұрын

How about make a new mood disorder instead of remaking the broken wheels that is antipsychotics. It’s so upsetting. I have little faith this will be helpful. And as someone who’s bipolar and the next in the pipeline of the sale and approval of this drug - I am horribly offended that drugs are not made for the bipolar that is massively bigger than schizophrenia. Do better. The drugs you’re pushing are marginally better than first gen antipsychotics. Maybe youd have higher compliance with drugs if they weren’t so awful to be on. How many people have to take Vrylar to actually be helped.

@baciliorochajr_schizophrenia 9 ай бұрын

I have schizophrenia 😢

@petercbrandon 8 ай бұрын

I wish you the best. My brother suffered with it and I wish we knew how to help him. He is a very loving and funny guy but he is very handicapped. The medication has hurt him and his consumption of sugar I believe has hurt him. He used to drink whole liters of Coke causing T2 diabetes. Please know people care about you and wish you well.

@baciliorochajr_schizophrenia 8 ай бұрын

@@petercbrandon 😢🆘

@rkr-420 7 ай бұрын

I have schizophrenia too, and I have sat down with chatGPT an advance artificial intelligence, an app on my phone to come up with theoretical ways we could possibly cure this disease. I have many more hypothetical/theoretical ways that could be possible solutions but here this list, it's one of many works I have done with the AI but the bad part is I have no help to do any of this. Hopefully it can help you bud, cheers. 1. Acupuncture 2. Ayurveda 3. Aromatherapy 4. Homeopathy 5. Naturopathy 6. Herbal medicine 7. Traditional Chinese Medicine 8. Yoga 9. Meditation 10. Chiropractic care 11. Tai Chi 12. Reiki 13. Hypnotherapy 14. Craniosacral Therapy 15. Shiatsu 16. Reflexology 17. Cupping therapy 18. Nutrition therapy 19. Energy healing 20. Holistic psychotherapy 21. Mindfulness-based stress reduction (MBSR) 22. Ayurvedic massage 23. Art therapy 24. Music therapy 25. Dance therapy 26. Pet therapy (animal-assisted therapy) 27. Hydrotherapy 28. Feldenkrais Method 29. Trager Approach 30. Alexander Technique 31. Pranic Healing 32. Chromotherapy (Color Therapy) 33. Sound Therapy 34. Crystal Healing 35. Polarity Therapy 36. Biomagnetic Therapy 37. Naturopathic manipulation 38. Biofeedback 39. Guided imagery 40. Qigong 41. Herbalism 42. Chakra balancing 43. Shamanic healing 44. Kinesiology 45. Tui Na massage 46. Lymphatic drainage massage 47. Auriculotherapy 48. Gua sha 49. Moxibustion 50. Magnet therapy 51. Theta healing 52. Flower essence therapy 53. Pranic Healing 54. Druidic Healing 55. Biofield Therapy 56. Radionics 57. Somatic Experiencing 58. Forrest Yoga 59. Watsu 60. Zen Shiatsu 61. Tai Yi 62. Visceral Manipulation 63. Pelvic Floor Therapy 64. Hakomi Therapy 65. Lomi Lomi 66. Zero Balancing 67. Systemic Constellations 68. Rebirthing-Breathwork 69. Sufi Healing 70. Somatic Experiencing 71. Core Energetics 72. Soul Talk 73. Mind-Body Medicine 74. Nature Therapy (Ecotherapy) 75. Acutonics 76. Bach Flower Remedies 77. Sujok Therapy 78. Yoga Nidra 79. Myofascial Release 80. Quantum Touch 81. Rolfing 82. Kampo 83. Earthing Therapy 84. Integrative Manual Therapy 85. Iridology 86. Ortho-Bionomy 87. Sufi Healing 88. Somatic Therapy 89. Emotion Code 90. Five Element Acupuncture 91. Jin Shin Jyutsu 92. Nambudripad's Allergy Elimination Technique (NAET) 93. Pranic Psychotherapy 94. Somatic Movement Therapy 95. Spiral Pranic Healing 96. Visceral Manipulation 97. Chios Energy Healing 98. Bowen Therapy 99. Kabbalistic Healing 100. Neuro-Linguistic Programming (NLP) 101. ThetaHealing 102. Tama-Do (Sound and Color Therapy) 103. Holographic Repatterning (Resonance Repatterning)

@El-wc5hl 7 ай бұрын

@@petercbrandon I have T2 and I believe it was caused by the anti-psychotics and antidepressants I've been on for 30 years.

@user-vb5pw6hl1m 7 ай бұрын

I do to