TP53INP2

A specific protein, TP53INP2, might prevent muscle loss associated with aging. A new study indicates that high levels of this protein are linked to greater muscle strength and healthier aging. This discovery paves the way for new treatments that could enhance the quality of life for the elderly. Sarcopenia, a prevalent condition among the elderly, is characterized by a progressive decline in muscle mass and function, which can significantly diminish their quality of life and increase the risk of falls, injuries, and dependency. A greater understanding of this phenomenon is crucial for devising effective strategies that enable the ageing population to remain healthy and independent. A study co-led by Dr. Antonio Zorzano, from IRB Barcelona, and Dr. David Sebastián, now a Professor at the University of Barcelona (UB), reveals that a protein named TP53INP2 could be pivotal in combatting sarcopenia. Conducted in partnership with Parc Sanitari Sant Joan de Déu, the study indicates that increased levels of this protein in muscle correlate with greater muscular strength and healthier ageing in humans. Loss of muscle mass typically starts around the age of 55, and it has a detrimental effect on people's ability to perform daily tasks and on their health. Sarcopenia leads to increased frailty physical disability and the need for long-term care. By conducting experiments on mouse models and analysing human muscle tissue samples, the researchers observed a decrease in TP53INP2 levels with age. However, artificially boosting the presence of this protein in muscles -- whether continuously in young mice or temporarily in older mice through genetic engineering techniques -- led to a significant improvement in both muscle mass and function. These findings suggest that promoting the activity of TP53INP2 and, consequently, autophagy in the muscle, could be an effective strategy to tackle sarcopenia, thereby contributing to a more active and healthier ageing process. In studies involving humans, high levels of TP53INP2 were associated with greater strength and enhanced physical performance, thereby highlighting the potential of this protein as an indicator of healthy ageing. "This study not only underscores the importance of keeping autophagy active in muscles to prevent muscle mass loss but also gives us hope regarding potential treatments that could improve the condition or at least mitigate the effects of ageing on our muscles," explains Dr. Zorzano, who is also a Professor at the Faculty of Biology at the UB and a member of CIBERDEM. "Furthermore, the activation of autophagy through TP53INP2 improved the quality of mitochondria, essential organelles in energy generation -- a process that we had previously shown to be disrupted during ageing," highlights Dr. Sebastián, Professor in the Department of Biochemistry and Physiology at the Faculty of Pharmacy and Food Sciences of the UB. The partnership with Parc Sanitari Sant Joan de Déu has been pivotal, providing access to biologic samples from well-characterized patients. This allowed the researchers to establish the link between TP53INP2 muscle expression and healthy ageing in humans. This advance not only paves the way for further research in ageing but also points to potential interventions to greatly improve the quality of life of seniors, helping them to maintain their independence and vitality. Moving forward, the researchers will continue to explore whether TP53INP2 levels in each person are influenced by genetic factors and physical activity, or, whether other habits, like nutrition, play a significant role. This work has been possible thanks to funding from the Ministry of Science, Innovation, and Universities, the Generalitat de Catalunya, and the Carlos III Health Institute.

SBS-518 is a dual sigma receptor antagonist/dopamine active transporter inhibitor in development for the treatment of stimulant use disorder (e.g., cocaine and methamphetamine) Grant awarded by National Institutes of Health / National Institute of Drug Abuse (NIH/NIDA) under the Help End Addiction Long-Term (HEAL) initiative NEW YORK, Aug. 08, 2023 (GLOBE NEWSWIRE) -- Sparian Biosciences, Inc. (“Sparian”), a clinical-stage CNS-focused biopharmaceutical company, today announced that it has been awarded a $19 million, five-year grant to fund development of SBS-518 from IND submission through Phase 1 clinical development. SBS-518 is a first-in-class dual sigma receptor (SR) antagonist/dopamine transporter (DAT) inhibitor in development for the treatment of stimulant use disorder (StUD). StUD is a subset of substance use disorders that includes cocaine and methamphetamine use disorders. The grant was awarded by NIH/NIDA under the Help End Addiction Long-Term (HEAL) initiative. SBS-518 is a novel first-in-class compound that targets within the brain both the sigma receptor (S1 and S2) and the dopamine active transporter (DAT). In pre-clinical efficacy assays, SBS-518 blocks the stimulant induced rise in extra-cellular dopamine and blocks cocaine and methamphetamine self-administration without itself producing self-rewarding behavior. DAT, the site of action for stimulants, including illicit stimulants, has proven to be an elusive target for therapeutics. The combination of sigma and DAT inhibition appears to block the action of methamphetamine and cocaine without interfering with the physiologic transport of dopamine. “Sparian was founded to develop innovative therapeutics to treat CNS disorders, particularly pain and substance use disorders,” said Jeff Reich, M.D., Chief Executive Officer and Co-founder. “StUD presents a major unmet medical and public health need for which there are currently no approved therapies. If we can successfully advance SBS-518 into the clinic, it could represent a significant step forward in the treatment of substance use disorders.” The $19 million dollars in funding represents the third NIH/NIDA grant Sparian has received. Since its founding, Sparian has been awarded a total of $41 million in government grants to support three programs. The lead program SBS1000, a non-opioid analgesic, is now in phase 1 clinical trials. SBS-226, a dual mu opioid receptor (MOR) agonist/delta opioid receptor (DOR) antagonist, is being developed for opioid use disorder (OUD). “We are extremely proud of the ongoing support we have received from NIDA,” said Dr. Reich. “NIDA, through the HEAL initiative, has sparked a new wave of innovation and entrepreneurship dedicated to the treatment of substance use disorders. Sparian, along with our academic partners, is honored to be a trusted collaborator.” SBS-518 is being developed in collaboration with the National Institute of Drug Abuse (NIDA), University of Florida College of Pharmacy, and the Harvard Medical School-McLean Hospital. About Stimulant Use Disorder (StUD) StUD represents a serious public health crisis in the U.S. with a growing prevalence of 4.1 million and approximately 57,000 annual deaths reported in 2021. There are no U.S. Food and Drug Administration-approved drugs to treat StUD. The current treatment approach includes off-label use of prescription therapies, such as antidepressants, and/or behavioral-psychosocial modalities. Only modest benefits have been demonstrated. It is estimated that only 13% of eligible patients are undergoing treatment of any kind reflecting the lack of effective medication. About Sparian Biosciences Sparian Biosciences is a clinical-stage CNS-focused biopharmaceutical company committed to developing transformational therapies to address significant medical needs. The company was co-founded by Jeff Reich, M.D., and Gavril Pasternak, M.D., Ph.D., and was spun out of Memorial Sloan Kettering Cancer Center (MSK). Sparian has five programs that address acute and chronic pain, opioid use disorder (OUD), acute opioid overdose, and stimulant use disorder (StUD). Sparian is the recipient of two NIDA UG3/UH3 grants and an SBIR grant totaling nearly $41M in NIH support. For more information, visit . Research reported in this press release was supported by the National Institute on Drug Abuse of the National Institutes of Health under award number 1UG3DA058553-01.The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health Contact: Annie Pasternak Chief Operating Officer annie@sparianbiosciences.com

PARIS — Relay Therapeutics had steadily raised the bar ahead of ESMO for RLY-4008, its bile duct cancer drug for a narrow group of patients with FGFR2-altered cholangiocarcinoma. And now it’s arriving in Paris with an improved performance that appears to pave a direct path to a quick approval. The bottom line from its ESMO abstract: Potent efficacy was observed across all doses, particularly at the RP2D (70mg QD) with an ORR of 88%. One pt treated at the RP2D had a near-complete response and subsequent tumor resection with curative intent. DOR is not yet mature, with majority of responses ongoing. Across all doses (N=195), the most common treatment-related AEs (TRAEs) were low-grade stomatitis (48%), PPE (46%), and dry mouth (31%). No grade 4/5 TRAEs were observed. Relay builds out case for anti-FGFR drug, shooting for first accelerated approval on 'motion-based' drug discovery platform That’s more than double the rate of response tracked for the pan-FGFR inhibitors now in use, notes Stifel’s Bradley Canino: The cORR of 82% is an increase from the previous data cut in June 2022, where 62% (8 of 13) FGFRi-naïve dose-escalation patients responded across all daily doses (20-70mg QD). In that cut, which was diluted by lower, less potent doses, there were 4 patients on 70mg, and all (100%) achieved a cPR. Competitively, The RLY-4008 efficacy is double or higher than the pan-FGFR inhibitor results of ~30-40% ORRs. The RLY-4008 profile strongly supports an accelerated approval opportunity in FGFRi-naïve FGFR2 fusion+ CCA, which will be supported by the ongoing n=100 expansion cohort from which several of the patients reported in the abstract are included. Cowen’s Yaron Werber sums it up this way: These data are solid, validate the platform, and are clearly differentiated. Relay went public $RLAY under CEO Sanjiv Patel after a celebratory $400 million round two years ago. And the IPO — highlighting its motion-based discovery platform — hit big at a time of general euphoria for all things biotech. Its share price has dropped 22% over the past year, but that’s a major improvement over the average debacle in this market, and it’s been trending green now with more upbeat data to take to the FDA. At the time it went public, Relay still played its R&D cards fairly close to its vest. But the confirmatory results researchers are rolling out this weekend leave them in a high-profile position, poised to take advantage of an FDA pathway that opens doors for drugs like this.