Acetylcholine Chloride

A team of researchers has uncovered new clues about how chemicals released by brain cells regulate our attention span. A team of researchers from Nanyang Technological University, Singapore (NTU Singapore) has uncovered new clues about how chemicals released by brain cells regulate our attention span. Findings from the study could pave the way for new therapies to treat neurological conditions associated with concentration difficulties, such as depression and attention-deficit hyperactivity disorder (ADHD). To communicate with one another, neurons in the brain and nervous system release chemicals called neurotransmitters that relay messages from one cell to another. Neurotransmitters are crucial for brain function and regulating all bodily functions, ranging from breathing and heart rate to reproduction. These chemicals also coordinate cognitive processes that enable us to focus on important information within the constant barrage of stimuli the brain receives from the external environment, otherwise known as our attention span. Researchers have long thought that our attention span was directed by only one neurotransmitter, acetylcholine, which excites neurons and causes them to fire electrical signals. However, recent work suggests that attention could require another neurotransmitter, gamma-aminobutyric acid (GABA), which inhibits neurons from receiving and sending messages. In their study published in the Proceedings of the National Academy of Sciences (PNAS), the team demonstrated for the first time that GABA works together with acetylcholine in a precise sequence to regulate the transmission of signals from a part of the brain's information processing network, called the claustrum. Hidden deep in the brain, the claustrum is a thin sheet-like structure that receives and processes information from different parts of it. The claustrum helps to regulate concentration, but its exact role remains unknown. Neurotransmitters toggle 'like a switch' to relay information In lab experiments, the NTU scientists investigated how neurons in the claustrum in mice respond to acetylcholine and GABA produced by a part of the brain called the forebrain, that plays a central role in several brain functions. The key technological advance that allowed the researchers to make this discovery is called optogenetics. Optogenetics uses light-sensitive proteins to selectively control the activity of specific types of neurons within the brain. In this case, the neurons within the forebrain that release acetylcholine and GABA were activated by light, allowing the team to measure the response of the claustrum to such a stimulus. They discovered that two types of neurons in the claustrum, which send output signals to different parts of the brain, respond in opposing ways to acetylcholine and GABA. Neurons that extend to structures deep in the brain were excited by acetylcholine while neurons that extend to structures on the surface of the brain were inhibited by GABA. Through this coordinated sequence of opposing actions, the two neurotransmitters toggle the transfer of information between the claustrum and the rest of the brain, like a switch. The study provides evidence that the neurotransmitters regulate a "microcircuit" in the brain, that allows the organ to differentiate important information from noise, helping a person pay attention. The opposing actions of the neurotransmitters (acetylcholine and GABA) on neurons in the claustrum enable brain signals to be encoded efficiently, allowing the brain to pay attention and ignore noise. First author Mr Aditya Nair, former researcher at LKCMedicine and a current Ph.D. student at Caltech, said, "Our study advances our understanding of the claustrum's role in directing attention span. Understanding how the claustrum regulates attention span at the cellular level also provides a window into other areas regulated by similar signalling pathways, such as arousal and learning." Lead investigator and neuroscientist Professor George Augustine from NTU's Lee Kong Chian School of Medicine (LKCMedicine) said, "By understanding how acetylcholine and GABA work together to direct our attention, new and more effective therapies may be developed in the future to improve the attention span of patients with conditions such as ADHD and depression." Commenting as an independent expert, Dr Geoffrey Tan, Consultant (Psychiatry) Clinician-Scientist at the Institute of Mental Health Singapore, said, "Directing attention and multi-tasking are crucial cognitive processes for everyday functioning that require toggling between networks or circuits in the brain. This study identifies a 'switch' in the claustrum that provides a mechanism by which acetylcholine may drive computations such as these. It is timely as we increasingly incorporate brain networks into how we think about cognition, psychiatric conditions and even interventions like mindfulness." The next steps for this project will be to determine how altering the dual-transmitter switch alters attention and brain disorders that affect attention, such as ADHD. It will also be important to determine whether the switch mechanism applies to other brain processes, such as arousal and learning.

- Provides Revance entry into the $2.5 billion U.S. therapeutic neuromodulator market. 1 - Approval expands the DAXXIFY® label to include efficacy data over the 52-week ASPEN repeat dose clinical study. - DAXXIFY® for cervical dystonia is the first and only peptide-formulated, long-lasting neuromodulator, designed to meet the needs of patients seeking improved treatment outcomes. 2-5 - 88% of U.S. cervical dystonia patients experience symptom reemergence eight to 10 weeks after conventional neuromodulator treatment. 6 NASHVILLE, TN, USA I August 14, 2023 I Revance Therapeutics, Inc. (Nasdaq: RVNC) today announced that the United States (U.S.) Food and Drug Administration (FDA) has approved the first therapeutic indication for DAXXIFY® (DaxibotulinumtoxinA-lanm) for injection for the treatment of cervical dystonia in adults. 7 DAXXIFY® , powered by Peptide Exchange Technology™, was previously approved by the FDA for the temporary improvement of glabellar lines (frown lines) in adults in September 2022 and is the first true innovation in neuromodulator product formulation in more than 30 years. 8-11 “We are very pleased to see the expansion of the DAXXIFY® label to include our first therapeutic indication, unlocking a new market opportunity for DAXXIFY® following the product’s recent launch in the aesthetics market. Further, we believe FDA approval represents a significant advancement in the treatment of cervical dystonia” Tweet this Cervical dystonia is a chronic, debilitating disease in which the neck muscles contract involuntarily, causing abnormal movements, pain and awkward posture of the head and neck. 12,13 Neuromodulators are considered the first line of treatment for this condition, which effects roughly 60,000 Americans. In 2017, the U.S. FDA granted orphan drug designation to DAXXIFY® for the treatment of cervical dystonia in adults. “We are very pleased to see the expansion of the DAXXIFY® label to include our first therapeutic indication, unlocking a new market opportunity for DAXXIFY® following the product’s recent launch in the aesthetics market. Further, we believe FDA approval represents a significant advancement in the treatment of cervical dystonia,” said Chief Executive Officer Mark J. Foley. “DAXXIFY’s differentiated efficacy, duration and safety profile can help physicians deliver long-lasting symptom relief to patients suffering from cervical dystonia, while also helping payers address the total cost of care for this population. We look forward to conducting our early experience and education program, PrevU, which will involve a small group of thought leaders, followed by a progressive commercial rollout beginning in 2024. Today’s approval is an important milestone for Revance, marking the start to our therapeutics franchise.” Peter McAllister, M.D., ASPEN investigator and co-founder and medical director of the New England Institute for Neurology and Headache, commented: “As an ASPEN investigator, I am excited to see the approval of a new treatment option to address symptom reemergence prior to retreatment, a common issue for cervical dystonia patients. Currently, patients experience painful and life-limiting symptom recurrence as early as eight to 10 weeks in clinical practice but cannot be re-treated until 12 weeks. DAXXIFY® is the first long-acting neuromodulator that has the potential to address this significant unmet need -- demonstrating durable symptom relief between treatment cycles and providing the opportunity to extend treatment intervals.” The U.S. approval of DAXXIFY® for the treatment of cervical dystonia in adults was based on data generated in the Phase 3 clinical program ( ASPEN 1 , ASPEN OLS ), which included 382 patients and 1,240 treatments across up to five injection cycles over an 88-week time span, based on the masked, randomized ASPEN-1 and ASPEN Open Label Study (OLS). 2-5 In the pivotal ASPEN clinical study, DAXXIFY® was shown to be effective, generally safe, and well tolerated across both dose groups, 125U and 250U, with a median duration of effect of 24.0 and 20.3 weeks for the two dose groups respectively. 2-3,14-15* Based on the ASPEN OLS study, symptoms continued to improve with successive DAXXIFY® treatments at doses up to 300U, while adverse events remained low. 15-16 In particular, dysphagia rates (difficulty swallowing) remained low (2.7% for ASPEN-1 and 4.2% for ASPEN-OLS), further supporting DAXXIFY’s safety profile. 15-16 The total U.S. therapeutic neuromodulator market opportunity for DAXXIFY® is $2.5 billion, which includes the $345 million cervical dystonia market. 1 Providers and patients interested in receiving more information on DAXXIFY® are encouraged to visit https://hcp.daxxify.com/ . *Median duration of effect was defined as time from treatment until loss of ≥80% of the peak effect (change from baseline in TWSTRS total score averaged across weeks four and six). DAXXIFY ® (DaxibotulinumtoxinA-lanm) injection IMPORTANT SAFETY INFORMATION INDICATIONS DAXXIFY® (DaxibotulinumtoxinA-lanm) injection is an acetylcholine release inhibitor and neuromuscular blocking agent indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adult patients and for the treatment of cervical dystonia in adults. Please see DAXXIFY® full Prescribing Information , including Boxed Warning and Medication Guide . To report side effects associated with DAXXIFY®, please visit safety.revance.com , or call 1-877-373-8669. You may also report side effects to the FDA at 1-800-FDA-1088 or visit www.fda.gov/medwatch . [DAXI-004726] About DAXXIFY® DAXXIFY® (DaxibotulinumtoxinA-lanm) for injection is the first and only FDA-approved, long-lasting, peptide-formulated neuromodulator product with approved indications in the U.S. for the temporary improvement of glabellar lines (frown lines) and for the treatment of cervical dystonia in adults. DAXXIFY® is powered by Peptide Exchange Technology™, Revance's proprietary, synthetic, 35-amino-acid stabilizing excipient, and is developed free of human serum albumin or animal-based components. 3,4 Manufactured in the U.S., DAXXIFY® is the first true innovation in neuromodulator product formulation in over 30 years. About Revance Revance is a biotechnology company setting the new standard in healthcare with innovative aesthetic and therapeutic offerings that enhance patient outcomes and physician experiences. Revance’s portfolio includes DAXXIFY® (DaxibotulinumtoxinA-lanm) for injection, the RHA® Collection of dermal fillers in the U.S., and value-added services including the OPUL® Relational Commerce platform for aesthetic practices. Revance has also partnered with Viatris Inc. to develop a biosimilar to onabotulinumtoxinA for injection and Shanghai Fosun Pharmaceutical to commercialize DAXXIFY® in China. Revance is headquartered in Nashville, Tenn., with additional office locations in Newark and Irvine, Calif. Learn more at www.Revance.com , www.RevanceAesthetics.com , www.DAXXIFY.com , https://hcp.daxxify.com/ , or connect with us on LinkedIn . “Revance” and the Revance logo, DAXXIFY®, and OPUL® are registered trademarks of Revance Therapeutics, Inc. Resilient Hyaluronic Acid® and RHA® are trademarks of TEOXANE SA. About Cervical Dystonia Cervical dystonia is a painful condition in which the neck muscles contract involuntarily, causing abnormal movements and awkward posture of the head and neck. The movements may be sustained (tonic), jerky (clonic), or a combination. Cervical dystonia (also referred to as spasmodic torticollis) may be primary (meaning that it is the only apparent neurological disorder, with or without a family history) or may be the result of secondary causes (such as physical trauma). First-line treatment for cervical dystonia is usually neuromodulator (botulinum toxin) injections, but additional treatments can include oral medications, surgery, and complementary therapies. Neuromodulators block the communication between the nerve and the muscle, relaxing the muscle, which alleviates abnormal involuntary movements and postures. Cervical dystonia can occur at any age, although most individuals first experience symptoms in middle age. Roughly 60,000 Americans suffer from this muscle movement disorder. SOURCES SOURCE: Revance Therapeutics