VIPR2

Schizophrenia is a serious mental health disorder linked to the imbalance of chemical neurotransmitters that affect cognitive capabilities. Current therapies against schizophrenia have numerous limitations, largely due to the selective permeability of blood-brain barrier, which necessitates the development of novel strategies. Schizophrenia is a complicated mental health disorder accompanied by wide range of symptoms such as hallucinations, impaired cognitive ability, and disorganized speech or behavior. It has been associated with anomalies in neurotransmission due to the imbalance of chemical neurotransmitters. Current treatment strategies against schizophrenia involve the administration of antipsychotic drugs, which can cause adverse effects and are associated with a high risk of cardiovascular disease. Moreover, in patients, response to therapeutic drugs is often inadequate as the blood-brain barrier (BBB), a protective barrier of cells, strictly regulates the movement of ions and molecules into the brain. To overcome the hurdle of BBB and facilitate the transport of therapeutic drugs into brain tissue to treat schizophrenia, researchers have explored the applicability of receptor-mediated transcytosis (RMT) using low-density lipoprotein receptor-related protein 1 (LRP1). This research was conducted by team led by Associate Professor Eijiro Miyako from Japan Advanced Institute of Science and Technology (JAIST), included Prof. Yukio Ago from Hiroshima University, Prof. Shinsaku Nakagawa from Osaka University, Prof. Takatsugu Hirokawa from Tsukuba University, and Dr. Kotaro Sakamoto, Senior Principal Scientist at Ichimaru Pharcos Co., Ltd. Their study was published in JACS Au journal on June 20, 2024. The researchers were inspired by previous findings which showed the interactions of vasoactive intestinal peptide receptor 2 (VIPR2) gene duplication in schizophrenia and their own discovery of a novel peptide, KS-133. The novel peptide, KS-133, has selective antagonist activity to VIPR2, leading to its downregulation. However, the major limitation associated with KS-133 was its poor permeability across BBB. To facilitate the effective transport of KS-133 into the brain, they developed a brain-targeting peptide, KS-487, that could specifically bind to LRP1 and influence RMT. Finally, the researchers developed a novel nanoparticle-based drug delivery system (DDS) where KS-133 peptide was encapsulated with KS-487 targeting peptide and studied its efficacy in treating schizophrenia. The administration of peptide formulations via the DDS resulted in the effective distribution of the drug in the brains of mice. Drug release profiles assessed by pharmacokinetic analysis confirmed the role of the brain-targeting peptide in transporting KS-133 into the brain. Furthermore, the efficacy of DDS was evaluated in mice with induced schizophrenia by elevated activation of VIPR2. Mice treated with KS-133/KS-487 nanoparticles showed significant improvement in cognitive functions during novel object recognition tests, which could be attributed to the inhibition of VIPR2. Explaining the real-life applications and potential of their study, Dr. Miyako shares, "Existing drugs only have mechanisms involving neurotransmitter modulation, and their therapeutic effects are limited, especially for cognitive dysfunction. Thus, our peptide formulation could be used as a novel drug to restore cognitive dysfunction in schizophrenia." In summary, this study by Dr. Miyako and co-researchers provides preclinical evidence of a novel therapeutic strategy for targeting VIPR2 that could improve cognitive impairment in schizophrenia. "Going ahead, we will extend our study to involve cells and animal models, as well as human clinical trials, to confirm the efficacy and safety of this peptide formulation and promote its development as a new treatment for schizophrenia within 5 years," concludes Dr. Miyako, optimistic about the long-term implications of their study.

CAMBRIDGE, MA, USA I February 17, 2023 I Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today announced that the first patient has been dosed in Study SRP-9003-102. Also known as VOYAGENE, Study 9003-102 is a phase 1 study of SRP-9003 (bidridistrogene xeboparvovec) for the treatment of limb-girdle muscular dystrophy Type 2E/R4 (LGMD2E). VOYAGENE is a U.S.-only study enrolling ambulant patients aged 18 years or older and non-ambulant patients, ages 4-50 years, using clinical process SRP-9003 material. “Sarepta has previously disclosed positive expression and function data from our initial clinical study, Study SRP-9003-101, exploring multiple doses of SRP-9003 in a younger, ambulant population. The VOYAGENE study, which also utilizes clinical material, provides an opportunity to generate additional data in a broader population of patients while we finalize plans for a global, Phase 3 study using commercially representative process material that we intend to begin later this year,” said Louise Rodino-Klapac, Ph.D., executive vice president, chief scientific officer and head of research and development, Sarepta Therapeutics. “Sarepta is applying lessons from across our gene therapy portfolio to help advance the development of our investigational LGMD programs as efficiently as possible. Current treatments for LGMD are limited to symptom management and we remain fully committed to working with urgency to bring forward new treatments that can slow the progression of this disease, improve mobility and enhance the quality of life for individuals living with LGMD2E and other LGMD subtypes.” More information on the VOYAGENE study is available at https://genesislgmd.com/study/voyagene . About SRP-9003 (bidridistrogene xeboparvovec) SRP-9003 (bidridistrogene xeboparvovec) is an investigational gene therapy that uses the AAVrh74 vector, which is designed to be systemically and robustly delivered to skeletal, diaphragm and cardiac muscle, making it an ideal candidate to treat peripheral neuromuscular diseases. SRP-9003 also uses the MHCK7 promoter, chosen for its ability to robustly express in the heart, which is critically important for patients with limb-girdle muscular dystrophy Type 2E (LGMD2E), also known as beta-sarcoglycanopathy and LGMDR4, many of whom die from pulmonary or cardiac complications. About Limb-girdle Muscular Dystrophy Limb-girdle muscular dystrophies are genetic diseases that cause progressive, debilitating weakness and wasting that begins in muscles around the hips and shoulders before progressing to muscles in the arms and legs. Sarepta’s six LGMD gene therapy programs in development include LGMD2E/R4, LGMD2D/R3, LGMD2C/R5, LGMD2B/R2, LGMD2L/R12 and LGMD2A/R1, which together represent more than 70 percent of known LGMD cases. Patients with LGMD2E begin showing neuromuscular symptoms such as difficulty running, jumping and climbing stairs before age 10. The disease, which is an autosomal recessive subtype of LGMD, progresses to loss of ambulation in the teen years and often leads to early mortality. There is currently no treatment or cure for LGMD2E. About Sarepta Therapeutics Sarepta is on an urgent mission: engineer precision genetic medicine for rare diseases that devastate lives and cut futures short. We hold leadership positions in Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophies (LGMDs), and we currently have more than 40 programs in various stages of development. Our vast pipeline is driven by our multi-platform Precision Genetic Medicine Engine in gene therapy, RNA and gene editing. For more information, please visit www.sarepta.com or follow us on Twitter , LinkedIn , Instagram and Facebook . SOURCE: Sarepta Therapeutics

CAMBRIDGE, Mass.--( BUSINESS WIRE )--Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today announced that the first patient has been dosed in Study SRP-9003-102. Also known as VOYAGENE, Study 9003-102 is a phase 1 study of SRP-9003 (bidridistrogene xeboparvovec) for the treatment of limb-girdle muscular dystrophy Type 2E/R4 (LGMD2E). VOYAGENE is a U.S.-only study enrolling ambulant patients aged 18 years or older and non-ambulant patients, ages 4-50 years, using clinical process SRP-9003 material. “ Sarepta has previously disclosed positive expression and function data from our initial clinical study, Study SRP-9003-101, exploring multiple doses of SRP-9003 in a younger, ambulant population. The VOYAGENE study, which also utilizes clinical material, provides an opportunity to generate additional data in a broader population of patients while we finalize plans for a global, Phase 3 study using commercially representative process material that we intend to begin later this year,” said Louise Rodino-Klapac, Ph.D., executive vice president, chief scientific officer and head of research and development, Sarepta Therapeutics. “ Sarepta is applying lessons from across our gene therapy portfolio to help advance the development of our investigational LGMD programs as efficiently as possible. Current treatments for LGMD are limited to symptom management and we remain fully committed to working with urgency to bring forward new treatments that can slow the progression of this disease, improve mobility and enhance the quality of life for individuals living with LGMD2E and other LGMD subtypes.” More information on the VOYAGENE study is available at https://genesislgmd.com/study/voyagene . About SRP-9003 ( bidridistrogene xeboparvovec ) SRP-9003 (bidridistrogene xeboparvovec) is an investigational gene therapy that uses the AAVrh74 vector, which is designed to be systemically and robustly delivered to skeletal, diaphragm and cardiac muscle, making it an ideal candidate to treat peripheral neuromuscular diseases. SRP-9003 also uses the MHCK7 promoter, chosen for its ability to robustly express in the heart, which is critically important for patients with limb-girdle muscular dystrophy Type 2E (LGMD2E), also known as beta-sarcoglycanopathy and LGMDR4, many of whom die from pulmonary or cardiac complications. About Limb-girdle Muscular Dystrophy Limb-girdle muscular dystrophies are genetic diseases that cause progressive, debilitating weakness and wasting that begins in muscles around the hips and shoulders before progressing to muscles in the arms and legs. Sarepta’s six LGMD gene therapy programs in development include LGMD2E/R4, LGMD2D/R3, LGMD2C/R5, LGMD2B/R2, LGMD2L/R12 and LGMD2A/R1, which together represent more than 70 percent of known LGMD cases. Patients with LGMD2E begin showing neuromuscular symptoms such as difficulty running, jumping and climbing stairs before age 10. The disease, which is an autosomal recessive subtype of LGMD, progresses to loss of ambulation in the teen years and often leads to early mortality. There is currently no treatment or cure for LGMD2E. About Sarepta Therapeutics Sarepta is on an urgent mission: engineer precision genetic medicine for rare diseases that devastate lives and cut futures short. We hold leadership positions in Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophies (LGMDs), and we currently have more than 40 programs in various stages of development. Our vast pipeline is driven by our multi-platform Precision Genetic Medicine Engine in gene therapy, RNA and gene editing. For more information, please visit www.sarepta.com or follow us on Twitter , LinkedIn , Instagram and Facebook . Internet Posting of Information We routinely post information that may be important to investors in the 'For Investors' section of our website at www.sarepta.com . We encourage investors and potential investors to consult our website regularly for important information about us. Forward-Looking Statements This press release contains “forward-looking statements.” Any statements that are not statements of historical fact may be deemed to be forward-looking statements. Words such as “believe,” “anticipate,” “plan,” “expect,” “will,” “may,” “intend,” “prepare,” “look,” “potential,” “possible” and similar expressions are intended to identify forward-looking statements. These forward-looking statements include statements relating to our potential to apply lessons from across our gene therapy portfolio to help advance the development of our investigational LGMD programs as efficiently as possible, our commitment to working with urgency to bring forward new treatments that can slow the progression of LGMD, improve mobility and enhance the quality of life for individuals living with LGMD 2E and other LGMD subtypes, and expected plans and milestones, including additional data from our VOYAGENE study and our plan to begin our potentially global Phase 3 study for SRP-9003 later this year. These forward-looking statements involve risks and uncertainties, many of which are beyond our control. Known risk factors include, among others: the possible impact of regulations and regulatory decisions by the FDA and other regulatory agencies on our business, as well as the development of our product candidates and our financial and contractual obligations; that we may not be able to execute on our business plans and goals, including meeting our expected or planned regulatory milestones and timelines, clinical development plans, and bringing our product candidates to market, due to a variety of reasons, some of which may be outside of our control, including possible limitations of company financial and other resources, manufacturing limitations that may not be anticipated or resolved for in a timely manner, regulatory, court or agency decisions, such as decisions by the United States Patent and Trademark Office with respect to patents that cover our product candidates, and the COVID-19 pandemic; success in pre-clinical trials and early clinical trials, especially if based on a small patient sample, does not ensure that later clinical trials will be successful; different methodologies, assumptions and applications we use to assess particular safety or efficacy parameters may yield different statistical results, and even if we believe the data collected from clinical trials of our product candidates are positive, these data may not be sufficient to support approval by the FDA or other global regulatory authorities; and those risks identified under the heading “Risk Factors” in Sarepta’s most recent Annual Report on Form 10-K for the year ended December 31, 2021, and most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) as well as other SEC filings made by the Company which you are encouraged to review. Any of the foregoing risks could materially and adversely affect the Company’s business, results of operations and the trading price of Sarepta’s common stock. For a detailed description of risks and uncertainties Sarepta faces, you are encouraged to review the SEC filings made by Sarepta. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release. Sarepta does not undertake any obligation to publicly update its forward-looking statements based on events or circumstances after the date hereof, except as required by law.