Encephalocele

Researchers have published new insights on pelvic floor muscle (PFM) dysfunction, which is one of the key risk factors for pelvic floor disorders, a set of morbid conditions that include pelvic organ prolapse and urinary and fecal incontinence, that impact close to a quarter of women in the U.S. and have a strong association with vaginal childbirth. The work is part of a larger effort to advance understanding, treatment and prevention of pelvic floor muscle dysfunction in humans. University of California San Diego researchers are leading a team reporting new insights in Science Translational Medicine on pelvic floor muscle (PFM) dysfunction, which is one of the key risk factors for pelvic floor disorders which impact close to a quarter of women in the U.S. Pelvic floor disorders are a set of conditions that include pelvic organ prolapse and urinary and fecal incontinence that have a strong association with vaginal childbirth. The UC San Diego team reports new direct evidence of both atrophy and fibrosis in the skeletal muscles of the pelvic floor of women with symptoms of pelvic organ prolapse. In addition, the team showed that in a well-established rat model for vaginal birth injury in humans, the pelvic floor muscles of the female rats sustained the same kinds of negative muscle transformations - atrophy and fibrosis - seen in the pelvic floor muscle biopsies of women. Finally, the UC San Diego team treated rats subjected to simulated birth injuries with an acellular injectable skeletal muscle extracellular matrix (ECM) hydrogel either at the time of or four weeks after simulated birth injury. They found that the administration of the hydrogel reduced the negative impact of the simulated birth injury on the rat pelvic floor muscles. The work, published in the August 02, 2023 issue of Science Translational Medicine, is part of a larger effort from this team of bioengineers, physician-scientists and basic scientists who are working together to advance understanding, treatment and prevention of pelvic floor muscle dysfunction in humans. Pelvic floor muscle damage "Understanding the natural pelvic floor muscle response after birth injury is crucial for developing and applying regenerative medicine approaches," said Pamela Duran, PhD, the first author on the paper. Duran recently completed her PhD in bioengineering at the University of California San Diego Jacobs School of Engineering. Duran is currently a postdoctoral researcher at the University of Michigan. "In this new work, we first investigated the pelvic skeletal muscles' short- and long-term responses after birth injury using a rat preclinical model. With these findings, we rationalized applying a cell-free biomaterial to prevent and treat the pathological changes of the pelvic floor muscle after simulated birth injury. The use of a low-cost and minimally invasive biomaterial is crucial for the clinical translation of this regenerative medicine approach to counteract the negative alterations of the pelvic floor muscles." In the new paper, the team presents new tissue-level research demonstrating that for cis-women who have given birth vaginally and have symptoms of pelvic organ prolapse, their pelvic floor muscles show the damage signs of atrophy and fibrosis - which includes the excess buildup of collagen. This new direct evidence of both atrophy and fibrosis in the skeletal muscles of the pelvic floor of women with symptoms of pelvic organ prolapse is an important step toward developing strategies to either prevent damage or aid recovery after damage occurs. This tissue-level research included samples from age-matched human cadavers as well as women undergoing surgery for pelvic organ prolapse. Insights from a preclinical model of birth injury "Current clinical and preclinical strategies for treating damaged pelvic floor muscles have focused on late stage treatments that are suboptimal for patients and do not address the underlying causes of muscle damage. In this preclinical research, we have shown that injecting a hydrogel directly into muscle tissue of the pelvic floor offers a potential method for encouraging and accelerating the natural healing process. In particular, we see the possibility of muscle fiber restoration rather than the unhealthy buildup of collagen," said Karen L. Christman, a professor in the Shu Chien-Gene Lay Department of Bioengineering at the UC San Diego Jacobs School of Engineering. Professor Christman is a cofounder, consultant, board member, and holds equity interest in Ventrix Bio Inc. and Kairos Technologies Inc. These two companies are working to translate biomaterial technologies into the clinic for applications including efforts to encourage regeneration of heart tissue and improved heart functionality after a heart attack, and prevent adhesions after cardiothoracic surgery. Learn more: This Injectable Biomaterial Heals Tissues from the Inside Out. Christman is also the Associate Dean for Faculty Affairs and Welfare at the UC San Diego Jacobs School of Engineering, where she holds the Pierre Galletti Endowed Chair for Bioengineering Innovation. In the Science Translational Medicine study, the team showed that in a well-established rat model for vaginal birth injury in humans, the pelvic floor muscles of the female rats sustained the same kinds of negative muscle transformations - atrophy and fibrosis - seen in the pelvic floor muscle biopsies of the women who have given birth and went on to develop pelvic floor prolapse. This finding serves to validate that additional research using this rat model of birth injury will be relevant for understanding and potentially finding better ways to treat or even prevent pelvic floor dysfunction and the associated pelvic floor disorders in women. A new approach for preventing or healing pelvic floor muscles "Pelvic skeletal muscles' birth injury and subsequent degeneration is a key risk factor for pelvic floor disorders that negatively impact lives on millions of women worldwide. Unfortunately, we know very little about tissue-level changes that take place in these important muscles as a result of maternal birth injury. The findings of our study are important because without understanding what goes wrong in pelvic floor muscles, we can't develop effective strategies to treat these important components of the pelvic floor," said Marianna Alperin, M.D., M.S. Professor of Obstetrics, Gynecology, and Reproductive Sciences, Professor of Urology, and Fellowship Research Director in the Division of Urogynecology & Pelvic Reconstructive Surgery at University of California San Diego. Dr. Alperin is also affiliated with the Sanford Consortium for Regenerative Medicine. In the study, the team showed that a tissue-specific cell-free pro-regenerative biomaterial, similar to the material invented at UC San Diego that is currently in clinical trials for helping to improve healing of heart tissue after heart attack, could serve as a new approach for helping to prevent or heal pelvic floor muscles injured during childbirth. In particular, the UC San Diego team treated rats subjected to simulated birth injuries with an acellular injectable skeletal muscle extracellular matrix (ECM) hydrogel either at the time of or four weeks after simulated birth injury. They found that the administration of the hydrogel reduced the negative impact of the simulated birth injury on the rat pelvic floor muscles. This new work highlights the need for further investigations of this promising biomaterial for the prevention of pelvic floor muscle dysfunction after birth injury. "Currently available preventative or therapeutic strategies are extremely limited and do not include regenerative approaches. While cell-based therapies are promising in many areas of medicine, they are associated with many hurdles, including substantial costs. In contrast, the biomaterial tested in our study does not contain any cells and is therefore very safe and is low-cost. Investigating what goes wrong in the pelvic skeletal muscles and developing pragmatic approaches to overcome these negative changes is very important for improving women's health," said Alperin.

Neurosurgeons from China review the latest literature from across the world to develop the consensus guidelines BEIJING, June 13, 2023 /PRNewswire/ -- Aneurysmal subarachnoid hemorrhage-related hydrocephalus (aSAH-H) is a clinical syndrome that leads to excessive accumulation of cerebrospinal fluid (CSF) and ventricle enlargement in the brain. aSAH-H is a complex pathophysiological syndrome, leadingto cognitive impairment and neurological damage. Acute hydrocephalus (less than 3 days of aSAH) can result in a fatal cerebral hernia, whereas chronic hydrocephalus (more than 3 days of aSAH) can adversely affect a patient's quality of life. Despite the complexity of this condition, there is a lack of diagnostic criteria and treatment protocol for aSAH-H, in China and abroad. Moreover, the lack of consensus among clinicians on the preferred treatment for aSAH-H calls for an urgent need for consistent standards. Prof. Shuo Wang from the Department of Neurosurgery at Beijing Tiantan Hospital, Capital Medical University, recently led an expert group from China to review and compose a consensus on the management of aSAH-H, based on the latest literature. The study was published in volume 9 of the Chinese Neurosurgical Journal on March 20, 2023. Dr. Hua Lu from the Department of Interventional Neuroradiology at Jiangsu Province Hospital along with Prof. Wang are the corresponding authors of this study. "Hydrocephalus is a common complication following aSAH and currently, the diagnosis and treatment of aSAH-H is clouded by a lack of clarity and inconsistency of standards. We wanted to make definite progress toward removing the ambiguity tied to its treatment," explains Prof. Wang. In terms of occurrence, the experts identified that aSAH-H is determined by the location of the aneurysm, intraventricular hemorrhage, and volume of the subarachnoid hemorrhage. Disturbances in CSF circulation drive the pathogenesis of aSAH-H, enlarge the ventricular system, and damage the brain's white matter. The experts concluded that age, volume of subarachnoid hemorrhage, the location and size of aneurysms are risk factors related to the occurrence of aSAH-H. The consensus states that the standard-of-care approach to diagnosis should include reviewing a patient's history of aSAH-H, identifying its clinical manifestations, and a head computed tomography scan to detect abnormal enlargement of the ventricles. Moreover, the consensus states that aSAH-H treatment should be aimed at releasing excessive intracranial pressure or addressing pathological changes to prevent further damage and loss of neurological function. This can include medications inhibiting CSF secretion or surgical interventions, such as CSF drainage, CSF shunt surgery, and CSF intracranial diversion. Furthermore, the consensus guideline recommends external ventricular drainage and ensuring the safe removal of the CSF drainage tube in the case of acute hydrocephalus. A ventriculoperitoneal shunt is recommended for cases of chronic hydrocephalus. The effectiveness of a shunt procedure can be confirmed with a positive lumbar puncture preceding surgery. Lastly, the consensus suggests measures to minimize postoperative complications. It recommends strict aseptic surgical procedures, anti-siphon and pressure-adjustable shunt catheters, monitoring of clinical manifestations, and use of imaging and laboratory examinations for management. Evincing hope about this development, Prof. Wang says, "This expert consensus applies to adults, but it's a good reference point for clinical diagnosis and treatment. Further research will certainly refine the process of aSAH-H diagnosis and treatment." Reference Title of original paper: Chinese expert consensus on the management of aneurysmal subarachnoid hemorrhage- related hydrocephalus Journal: Chinese Neurosurgical Journal DOI View original content to download multimedia: SOURCE Chinese Neurosurgical Journal

Preclinical data demonstrate potential efficacy and safety of OV329 at low, chronic dosing, suggesting an improved pro to other GABA-aminotransferase inhibitors Data from the NIH/NINDs Epilepsy Therapy Screening Program demonstrate that OV329 confers protection from seizure activity in several treatment-resistant animal models New preclinical data on OV350 underscore the potential of activating the KCC2 to alleviate refractory status epilepticus and limit neuronal damage NEW YORK, Dec. 02, 2022 (GLOBE NEWSWIRE) -- Ovid Therapeutics Inc. (NASDAQ: OVID), a biopharmaceutical company developing medicines designed to conquer epilepsies and meaningfully improve the lives of people affected by brain disorders, today announced that preclinical data supporting its OV329 and OV350 programs in epilepsy and treatment-resistant seizures will be presented at the 2022 American Epilepsy Society (AES) Annual Meeting, taking place December 2-6 in Nashville, Tennessee. “We are excited to return to AES with encouraging preclinical data supporting the anti-seizure potential of what we anticipate will be a first-in-class KCC2 program and best-in-class program for GABA-aminotransferase inhibitors. If successful, these programs will provide hope for people with treatment-resistant epilepsies,” said Jeremy Levin, D. Phil, MB BChir and Chairman and Chief Executive Officer of Ovid Therapeutics. “Our pipeline of potential medicines is designed with unique mechanisms of action to address the diverse, underlying pathophysiology of seizures. Our data suggest OV329 to be a potent, next-generation GABA-AT inhibitor with the potential for seizure reduction with chronic, low dosing. Data presented on OV350 support the therapeutic opportunity associated with activating KCC2, a novel target in epilepsy.” Posters to be presented on Ovid development programs are listed here: Title: Evaluation of OV329, a next-generation GABA-AT inhibitor in a series of pharmaco-resistant seizure models through the NINDS Epilepsy Therapy Screening Program Session Date & Time: 12-2 p.m. CST, Sunday, December 4 Presenter: Patrick Sarmiere, Ph.D. Poster Number: #2.215 Summary: Using the NIH/NINDS Epilepsy Therapy Screening Program (ETSP), a series of signal-finding studies using multiple mouse seizure models, found that OV329 demonstrated efficacy in the subacute models of epilepsy, including corneal kindling model (CKM) and mesial temporal lobe epilepsy (MTLE) model, though it did not mitigate seizures in the 6 Hz psychomotor seizures and maximal electroshock seizures (MES) at the doses tested. In the CKM and MTLE models, a single, high dose of OV329 produced near-complete protection from seizure activity. This pattern is analogous to the effects of vigabatrin and supports additional studies to evaluate repeat dosing at lower dose levels in CKM models. Title: OV329, a next-generation GABA-AT inhibitor, suppresses hippocampal paroxysmal discharges following repeat dosing in a mouse model of mesial temporal lobe epilepsy Session Date & Time: 12-2 p.m. CST, Sunday, December 4 Presenter: Jay Mukherjee, Ph.D. Poster Number: #2.213 Summary: In the MTLE model, a once daily 3.0 mg/kg dose of OV329 administered for eight days significantly reduced the number of seizures by Day 4, with maximum reduction at Day 8, compared to baseline. Furthermore, changes in baseline seizures persisted for seven days following the last administration. Findings demonstrate repeat administration of 3.0 mg/kg is at least as efficacious as a single 10 mg/kg dose of OV329. Title: Direct activation of KCC2 with OV350 arrests refractory status epilepticus and limits the subsequent neuronal injury Session Date & Time: 12-1:45 p.m. CST, Monday, December 5 Presenter: Shu Fun Josephine Ng, Ph.D. Poster Number: #3.278 Summary: OV350 binds with high affinity to KCC2, potassium chloride cotransporter isoform 2, and increases its activity, reducing neuronal Cl- accumulation and limiting the development of hyperexcitability. Additionally, OV350 restored the efficacy of benzodiazepines to treat refractory epilepsies and limit associated brain injuries. In addition, posters characterizing the mechanism of action of soticlestat and other supportive studies are anticipated to be presented by Takeda Pharmaceuticals. Ovid out-licensed soticlestat to Takeda, which is currently evaluating soticlestat in two pivotal, Phase 3 trials for Dravet and Lennox-Gastaut syndromes. About Ovid Therapeutics Ovid Therapeutics Inc. is a New York-based biopharmaceutical company striving to conquer seizures and brain disorders with courageous science. Ovid’s pipeline of small molecule and genetic medicines candidates seek to meaningfully improve the lives of people and families affected by epilepsies. Ovid is developing OV329, a GABA-aminotransferase inhibitor, for treatment-resistant seizures, and OV350, a direct activator of the KCC2 transporter, for potential treatment of epilepsies. In addition, Ovid maintains a significant financial interest in the future regulatory development and potential commercialization of soticlestat, which Takeda is responsible for advancing globally. Soticlestat is a cholesterol 24-hydroxylase inhibitor, which is currently in Phase 3 trials for Dravet and Lennox-Gastaut syndromes. For more information about these and other Ovid research programs, please visit Forward-Looking Statements This press release includes certain disclosures that contain “forward-looking statements,” including, without limitation: statements regarding the potential development and use of OV329; the likelihood that data for OV329 will support future development and therapeutic potential; the potential use and development of OV350 and other KCC2 compounds in the Company's library; the suitability of the Company’s library of novel, direct KCC2 transporter activators for a range of formulations and administrations and the timing and status of Takeda’s two pivotal Phase 3 trials evaluating soticlestat for Lennox-Gastaut and Dravet syndromes. You can identify forward-looking statements because they contain words such as "anticipates," "believes," "expected," "intends," "plan," "potentially," and "will," and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances). Forward-looking statements are based on Ovid’s current expectations and assumptions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that may differ materially from those contemplated by the forward-looking statements, which are neither statements of historical fact nor guarantees or assurances of future performance. Important factors that could cause actual results to differ materially from those in the forward-looking statements include, without limitation, uncertainties inherent in the preclinical and clinical development and regulatory approval processes, the risk that Ovid may not be able to realize the intended benefits of its technology and risks to Ovid’s or any of its partners’ abilities to meet anticipated deadlines and milestones presented by the ongoing COVID-19 pandemic. Additional risks that could cause actual results to differ materially from those in the forward-looking statements are set forth under the caption “Risk Factors” in Ovid’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 8, 2022, and in future filings Ovid makes with the SEC. Any forward-looking statements contained in this press release speak only as of the date hereof, and Ovid assumes no obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as otherwise required by law. Contacts Investors and Media: Ovid Therapeutics Inc. Meg Alexander 917-943-6681 malexander@ovidrx.com OR Investors: Argot Partners Maeve Conneighton 212-596-7231 ovid@argotpartners.com