somatostatin

- ZONE study to evaluate the effect of ZT-01 on preventing nighttime hypoglycemia in people with Type 1 diabetes - - ZT-01 has the potential to become the first therapeutic to prevent nocturnal hypoglycemia, a condition for which there are currently no available therapies - TORONTO, Sept. 25, 2023 /PRNewswire/ -Zucara Therapeutics Inc., ("Zucara" or the "Company") a diabetes life sciences company developing the first once-daily therapeutic to prevent hypoglycemia (low blood glucose levels) in people with diabetes, today announced that it has dosed the first patient in its Phase 2a trial of the effect of ZT-01 On Nocturnal hypoglycemia Events in Type 1 diabetes ("T1D") mellitus ("ZONE"). "Dosing the first patient in Zucara's ZONE trial is the Company's most significant milestone to date, and advances what could be the first preventative solution to potentially dangerous nighttime low blood glucose levels," said Michael Midmer, Zucara Therapeutics' Chief Executive Officer. "Nighttime hypoglycemia remains a significant challenge in diabetes management and is a great source of fear for people with diabetes, parents and their caregivers. We believe ZT-01 could greatly improve quality of life by preventing these low blood sugar events which are an ongoing disruption to many people with T1D and can lead to serious complications and poorer health outcomes." The ZONE study is a multi-centre, randomized, double-blinded, placebo-controlled, multiple-dose, crossover study designed to evaluate the effect of ZT-01 on the frequency of nocturnal hypoglycemia in patients with T1D. Patients will self-administer one of three doses of ZT-01, or placebo, every evening before bed each for a four-week period. Patients will be monitored for hypoglycemia events using a continuous glucose monitor. The study's primary endpoint is the rate of nocturnal hypoglycemic events, compared to placebo. Secondary endpoints include the number of patients experiencing adverse events and time spent in hypoglycemia compared to placebo. Dr. Alex Abitbol, who previously evaluated ZT-01 in a Phase 1b study and will be a principal investigator for ZONE, commented, "The positive results from the proof-of-concept Phase 1b study of ZT-01 were intriguing: in addition to observing a rise in glucagon, we also saw a corresponding rise in glucose during hypoglycemia. This suggests that ZT-01 can prevent nocturnal hypoglycemia, which is what we aim to confirm in the ZONE trial." The ZONE study is actively recruiting and will enroll patients at as many as 15 clinical sites across Canada and the U.S. Recruitment is expected to be completed in 2024. Zucara previously announced positive results from its proof-of-concept Phase 1b study of ZT-01 in people with T1D demonstrating that nearly 90% of patients had a meaningful increase in glucagon release following ZT-01 administration, compared to placebo, with no serious adverse events observed. About ZT-01 ZT-01 is designed to prevent potentially dangerous low blood glucose by restoring the body's ability to counterregulate hypoglycemia. In people without diabetes, α-cells secrete glucagon that signals the body to release its own glucose stores to prevent or reverse hypoglycemia. However, in people with insulin-dependent diabetes – including those with T1D and insulin-dependent Type 2 diabetes – evidence suggests that elevated secretion of pancreatic somatostatin suppresses glucagon release from α-cells. Zucara has demonstrated that, in people with T1D, the glucagon response can be increased with ZT-01, a first-in-class SST receptor 2 antagonist. About Zucara Therapeutics Inc. Zucara Therapeutics is developing ZT-01, a first-in-class, once-daily therapeutic to prevent hypoglycemia in people with T1D and insulin-dependent Type 2 diabetes. ZT-01 is designed to inhibit somatostatin, a pancreatic hormone that impairs the glucagon response to hypoglycemia in people with these conditions. ZT-01 is designed to restore glucagon secretion to prevent hypoglycemia, which could dramatically change diabetes disease management and improve both patient health and quality of life. For more information, visit .

- Award to provide US$2 million to support Zucara's planned Phase 2a ZONE trial, with first patient dosing expected in Q3 2023 - TORONTO, June 15, 2023 /PRNewswire/ - Zucara Therapeutics Inc., ("Zucara" or the "Company") a diabetes-focused life sciences company developing the first once-daily therapeutic to prevent hypoglycemia (low blood glucose levels) in people with diabetes, today announced additional funding from JDRF, the leading global Type 1 diabetes ("T1D") research and advocacy organization. Through its Industry Discovery & Development Partnerships ("IDDP") program, JDRF will provide US$2 million in funding to support Zucara's planned Phase 2a study of the effect of ZT-01 On Nocturnal hypoglycemia Events in Type 1 diabetes mellitus ("ZONE"). Zucara expects to begin patient dosing in the third quarter of 2023. "JDRF has been a long-time partner of Zucara, supporting the development of ZT-01 from early discovery studies to this planned Phase 2 study soon underway," said Richard Liggins PhD, Zucara Therapeutics' Chief Scientific Officer. "We are grateful for JDRF's ongoing support. This funding underscores JDRF's prioritization of advancing adjunctive therapies to insulin reflecting a continuing unmet need for T1D patients. We are hopeful that the ZONE study will demonstrate that ZT-01 can prevent potentially dangerous and disruptive low blood glucose levels overnight, and lead to the first therapeutic to treat this unintended consequence of insulin therapy." "Hypoglycemia remains a significant clinical challenge for people with T1D. Moreover, fear of hypoglycemia has great impact on quality of life for people with T1D and their caregivers. Therapies to prevent recurrent hypoglycemia, particularly overnight, are greatly needed," said Courtney Ackeifi, PhD, senior scientist at JDRF. "JDRF is excited to support Zucara's development of a novel therapy with the potential to protect against nocturnal hypoglycemia and help people with T1D achieve better glucose control." About ZT-01 ZT-01 is designed to prevent potentially dangerous low blood glucose levels by restoring the body's ability to counter-regulate hypoglycemia. In people without diabetes, α-cells secrete glucagon that signals the body to release its own glucose stores, thus preventing hypoglycemia. However, in people with insulin-dependent diabetes – including those with T1D and insulin-dependent Type 2 diabetes – evidence suggests that elevated secretion of pancreatic somatostatin ("SST") suppresses glucagon release from α-cells. Zucara has demonstrated that, in people with T1D, the glucagon response can be increased with ZT-01, a first-in-class SST receptor 2 antagonist. About Zucara Therapeutics Inc. Zucara Therapeutics is developing ZT-01, a first-in-class, once-daily therapeutic to prevent hypoglycemia in people with T1D and insulin-dependent Type 2 diabetes. ZT-01 is designed to inhibit somatostatin, a pancreatic hormone that impairs the glucagon response to hypoglycemia in people with these conditions. ZT-01 is designed to restore glucagon secretion to prevent hypoglycemia, which could dramatically change diabetes disease management and improve both patient health and quality of life. For more information, visit . About JDRF JDRF's mission is to accelerate life-changing breakthroughs to cure, prevent and treat T1D and its complications. To accomplish this, JDRF has invested more than $2.5 billion in research funding since our inception. We are an organization built on a grassroots model of people connecting in their local communities, collaborating regionally and globally for efficiency and broader fundraising impact, and uniting on a global stage to pool resources, passion, and energy. We collaborate with academic institutions, policymakers, and corporate and industry partners to develop and deliver a pipeline of innovative therapies to people living with T1D. Our staff and volunteers throughout the United States and our five international affiliates are dedicated to advocacy, community engagement, and our vision of a world without T1D. For more information, please visit jdrf.org or follow us on Twitter (@JDRF), Facebook (@myjdrf), and Instagram (@jdrfhq). About Type 1 Diabetes (T1D) T1D is an autoimmune condition that causes the pancreas to make very little insulin or none at all. This leads to dependence on insulin therapy and the risk of short or long-term complications, which can include highs and lows in blood sugar; damage to the kidneys, eyes, nerves, and heart; and even death if left untreated. Globally, it impacts nearly 9 million people. Many believe T1D is only diagnosed in childhood and adolescence, but diagnosis in adulthood is common and accounts for nearly 50% of all T1D diagnoses. The onset of T1D has nothing to do with diet or lifestyle. While its causes are not yet entirely understood, scientists believe that both genetic factors and environmental triggers are involved. There is currently no cure for T1D. SOURCE Zucara Therapeutics Inc.

Heavy alcohol consumption may cause permanent dysregulation of neurons, or brain cells, in adolescents, according to a new study in mice. The findings suggest that exposure to binge-levels of alcohol during adolescence, when the brain is still developing, lead to long-lasting changes in the brain's ability to signal and communicate -- potentially setting the stage for long-term behavioral changes and hinting towards the mechanisms of alcohol-induced cognitive changes in humans. Heavy alcohol consumption may cause permanent dysregulation of neurons, or brain cells, in adolescents, according to a new study in mice. The findings suggest that exposure to binge-levels of alcohol during adolescence, when the brain is still developing, lead to long-lasting changes in the brain's ability to signal and communicate -- potentially setting the stage for long-term behavioral changes and hinting towards the mechanisms of alcohol-induced cognitive changes in humans. "What we're seeing here," said Nikki Crowley, assistant professor in biology and biomedical engineering and Huck Early Chair in Neurobiology and Neural Engineering, "is that if adolescent binge drinking knocks neurons off this trajectory, they might not be able to get back, even if the alcohol consumption stops." The prefrontal cortex is a key brain region for executive functioning, risk assessment and decision-making. According to Crowley, it's not fully formed in adolescents and is still maturing in humans until around age 25. Disruptions to its development in young people may have serious and long-lasting consequences, added Crowley. "Heavy binge drinking is problematic for everyone, and should be avoided, but adolescent brains appear to be particularly vulnerable to the consequences, which in humans, will follow them for decades," Crowley said. The team, led by Avery Sicher, a doctoral student in Penn State's neuroscience program, used a model of adolescent ethanol exposure in mice to understand how different populations of neurons in the cortex, the outermost layer of the brain, are changed by voluntary binge alcohol consumption. In this model, mice are known to consume alcohol in patterns that approximate human binge drinking -- defined by the National Institute on Alcohol Abuse and Alcoholism as a pattern of alcohol consumption that leads to a blood alcohol concentration of 0.08% or higher, usually in about two hours. Binge drinking is considered to be one of the most dangerous patterns of alcohol misuse, and understanding its impact on the developing brain can help inform treatment. Sicher and her colleagues gave mice access to alcohol during a 30-day period. Due to their faster development and shorter lifespan, this corresponded to roughly ages 11-18 in human years. They then looked at the electrophysiological properties of different neurons throughout the prefrontal cortex to understand how adolescent binge drinking influenced the wiring and firing of these circuits. Sicher et al. used whole-cell patch clamp electrophysiology, combined with techniques such as optogenetics, which allowed the team to isolate individual neurons and record measurements related to intrinsic excitability, such as the resting membrane potential and the ability for each neuron to fire action potentials. This allowed them to understand how these neurons had changed their ability to signal with other neurons. They found that somatostatin neurons, a key population of cells that provides inhibition of neurotransmitter release from other cell types throughout the brain and helps to "dampen the noise," appeared to be permanently dysregulated in the mice that binge drank as compared to mice that were only provided water throughout development. Somatostatin neurons release both inhibitory neurotransmitters, like GABA, as well as inhibitory peptides like somatostatin, and proper functioning of these neurons is necessary for a healthy brain. The neurons were more excitable -- meaning they were signaling too much and dampening the activity of other key neurons -- as far out as 30 days after the mice stopped drinking alcohol, when the mice have transitioned into adulthood. "Neurons have a relatively fixed developmental trajectory -- they need to get where they are going and sync up with the right partners during specific periods of development in order to function properly," explained Crowley. David Starnes, an undergraduate biology student in Schreyer's Honor College, performed somatostatin cell counts to quantify cell density before and after ethanol consumption. He found that while the electrophysiology data suggested these neurons wire differently, the number of SST neurons does not appear to change as a result of binge drinking. Other authors on the paper include Keith Griffith, a research technician in the lab and former undergraduate in Engineering Science and Mechanics, Grace Smith, a graduate student in Biomedical Engineering, Dakota Brockway, a graduate student in neuroscience, and Nigel Dao, a former research technician in the lab and current doctoral student at New York University. This research was supported by the National Institutes of Health and the Huck Institutes of the Life Sciences at Penn State.