GluK2

THURSDAY, Dec. 12, 2024 -- It's still early science -- studies in mice and in human cells -- but researchers are on the trail of an effective new treatment for inflammatory skin conditions such as rosacea . Skin cells called mast cells are key players in the inflammation and itchiness that can plague folks with these skin ailments. However, researchers at the University of Pittsburgh report they've spotted a compound called SYM2081 that can quiet down these overactive cells. “I’m really excited about the clinical possibilities of this research,” said senior study author Dr. Daniel Kaplan , a professor of dermatology and immunology at the university. “Currently, there aren’t a lot of good therapies that target mast cells, so we think that our approach could potentially have huge benefits in many skin conditions, including rosacea, eczema, urticaria [hives] and mastocytosis [a rare genetic disorder that causes the body to produce too many mast cells].” His team published its findings Dec. 11 in the journal Science Translational Medicine . Anyone with hay fever or other allergies has heard of histamines; cellular compounds that can trigger or signal the misery of inflammation. According to Kaplan's team, mast cells contain "granules" loaded with histamines (and other pro-inflammatory agents). When these granules tear open, that can trigger a cascade of inflammatory immune responses such as those seen in rosacea or eczema. Granule rupture is beneficial when the threat to the skin is real and a quick immune response is needed -- a bee sting, for example. However, out-of-control granule rupture and histamine activity is at the root of allergic reactions like swelling, hives and itchiness, the researchers explained. Kaplan's team had already discovered that mast cells can recognize a compound called glutamate, which appears to keep the cells from going into overdrive. When they "switched off" the mast cell receptor that was targeted to glutamate, mast cells became hyperactive. “This finding led us to wonder if doing the opposite would have a beneficial effect,” Kaplan said in a university news release. “If we activate the glutamate receptor [Gluk2], maybe we can suppress mast cell activity and inflammation.” The newly discovered compound, SYM2081, appears to do just that. In experiments conducted in mice and in human cells, SYM2081 activated the glutamate receptor on mast cells, quieting things down. For example, mice prone to rosacea- or eczema-like symptoms had much milder outbreaks of the disease if they had been treated with a cream containing SYM2081, Kaplan's team found. Rosacea is a common skin malady characterized by a thickening of the skin, pimples, broken blood vessels and facial redness. Could treating rosacea with an SYM2081-bearing cream ease inflammation, itchiness and swelling in people, as well? That remains to be seen, the team said. “Although there are excellent therapies available for different types of rosacea, many are antibiotic-based and they only target some of the symptoms,” Kaplan noted. “There are no good therapies for [rosacea-linked] flushing, so this is a significant unmet need. Our study suggests that suppressing mast cells by activating GluK2 could reduce the flushing associated with rosacea.” The new study was funded by the U.S. National Institutes of Health. Kaplan's team has already applied for a patent for the potential new therapy, and clinical trials in patients are planned. Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

Nov. 21, 2024 -- uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today announced that the first patient has been dosed in the GenTLE Phase I/IIa clinical trial of AMT-260 for the treatment of refractory mesial temporal lobe epilepsy (MTLE). “The dosing of the first patient in our Phase I/II trial in temporal lobe epilepsy represents an important milestone for uniQure and our third clinical trial initiation over the past six months,” stated Walid Abi-Saab, M.D., chief medical officer of uniQure. “Nearly one-third of people experiencing focal onset seizures do not respond to currently available treatments and are left with limited therapeutic options. Our investigational agent, AMT-260, which is a one-time administration, has the potential to be a transformative treatment option for these patients. We continue to actively screen patients for the trial and look forward to providing program updates in the new year.” AMT-260 consists of an AAV9 vector that locally delivers two engineered miRNAs designed to reduce the expression of GluK2 protein subunits, a subtype of glutamate receptor that is believed to be aberrantly expressed in the hippocampus of patients with refractory MTLE and believed to trigger their seizure activity. In preclinical animal studies, AMT-260 reduced the number of seizures per day in a dose-dependent manner. AMT-260 also reduced the expression of GluK2 mRNA and protein in the hippocampus of epileptic mice and from resected hippocampal slices from patients with refractory MTLE. GenTLE is a Phase I/IIa multi-center, open-label trial being conducted in the U.S. to evaluate the safety, tolerability and exploratory signs of efficacy of two doses of AMT-260 in individuals with refractory MTLE. The study comprises two dose cohorts of six patients each. The study is actively recruiting though 10 sites with an additional two sites expected to be activated by the end of 2024. Additional details are available on www.clinicaltrials.gov (NCT06063850). Temporal lobe epilepsy is a chronic neurologic disorder and is the most common form of focal epilepsy with more than 600,000 individuals suffering from the disorder in the United States. Approximately 80% of all temporal lobe epilepsy cases are mesial, which involves the medial (or internal) structures of the brain. The majority of MTLE cases are refractory to anti-seizure medications, which severely limits treatment options. uniQure’s mission is to reimagine the future of medicine by delivering innovative cures that transform lives. The recent approvals of our gene therapy for hemophilia B – a historic achievement based on more than a decade of research and clinical development – represent a major milestone in the field of genomic medicine and ushers in a new treatment approach for patients living with hemophilia. We are now leveraging our modular and validated technology and manufacturing platform to advance a pipeline of proprietary gene therapies for the treatment of patients with Huntington's disease, refractory mesial temporal lobe epilepsy, amyotrophic lateral sclerosis (ALS), Fabry disease, and other severe diseases. www.uniQure.com The content above comes from the network. if any infringement, please contact us to modify.

LEXINGTON, MA, USA and AMSTERDAM, The Netherlands I November 21, 2024 I uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today announced that the first patient has been dosed in the GenTLE Phase I/IIa clinical trial of AMT-260 for the treatment of refractory mesial temporal lobe epilepsy ( MTLE ). “The dosing of the first patient in our Phase I/II trial in temporal lobe epilepsy represents an important milestone for uniQure and our third clinical trial initiation over the past six months,” stated Walid Abi-Saab, M.D., chief medical officer of uniQure . “Nearly one-third of people experiencing focal onset seizures do not respond to currently available treatments and are left with limited therapeutic options. Our investigational agent, AMT-260, which is a one-time administration, has the potential to be a transformative treatment option for these patients. We continue to actively screen patients for the trial and look forward to providing program updates in the new year.” AMT-260 consists of an AAV9 vector that locally delivers two engineered miRNAs designed to reduce the expression of GluK2 protein subunits, a subtype of glutamate receptor that is believed to be aberrantly expressed in the hippocampus of patients with refractory MTLE and believed to trigger their seizure activity. In preclinical animal studies, AMT-260 reduced the number of seizures per day in a dose-dependent manner. AMT-260 also reduced the expression of GluK2 mRNA and protein in the hippocampus of epileptic mice and from resected hippocampal slices from patients with refractory MTLE. GenTLE is a Phase I/IIa multi-center, open-label trial being conducted in the U.S. to evaluate the safety, tolerability and exploratory signs of efficacy of two doses of AMT-260 in individuals with refractory MTLE. The study comprises two dose cohorts of six patients each. The study is actively recruiting though 10 sites with an additional two sites expected to be activated by the end of 2024. Additional details are available on www.clinicaltrials.gov (NCT06063850). About Refractory Mesial Temporal Lobe Epilepsy Temporal lobe epilepsy is a chronic neurologic disorder and is the most common form of focal epilepsy with more than 600,000 individuals suffering from the disorder in the United States. Approximately 80% of all temporal lobe epilepsy cases are mesial, which involves the medial (or internal) structures of the brain. The majority of MTLE cases are refractory to anti-seizure medications, which severely limits treatment options. About uniQure uniQure’s mission is to reimagine the future of medicine by delivering innovative cures that transform lives. The recent approvals of our gene therapy for hemophilia B – a historic achievement based on more than a decade of research and clinical development – represent a major milestone in the field of genomic medicine and ushers in a new treatment approach for patients living with hemophilia. We are now leveraging our modular and validated technology and manufacturing platform to advance a pipeline of proprietary gene therapies for the treatment of patients with Huntington’s disease, refractory mesial temporal lobe epilepsy, amyotrophic lateral sclerosis (ALS), Fabry disease, and other severe diseases. www.uniQure.com SOURCE: uniQure