A Randomized, Double-Blind, Sparing-effect Placebo Controlled, With Cross-over Study to Evaluate the Safety, Tolerability and Efficacy of SCI-210 in Children With Autism Spectrum Disorder (ASD)

To evaluate the safety and efficacy of SCI-210 in the treatment of Autism Spectrum Disorders (ASD)

Start Date01 Sep 2023

Sponsor / Collaborator

SciSparc Ltd.

NCT05766969 / Unknown statusPhase 1/2

A Randomized, Double-Blind, Placebo-Controlled Trial Using Cannabidiol and Palmitoylethanolamide for the Treatment of Painful Diabetic Peripheral Neuropathy of the Feet

The purpose of the study is to evaluate whether the DIA/NPR-6 is a better pain reliever in patients with diabetic neuropathic pain of the feet compared to placebo.

Start Date05 Jun 2023

Sponsor / Collaborator

Pure Green Pharmaceuticals, Inc.

NCT02645461 / CompletedNot ApplicableIIT

Acetylcholine Receptors From Human Muscles as Pharmacological Target for ALS

Amyotrophic lateral sclerosis (ALS) is a fatal disease leading to motor neuron degeneration and progressive paralysis. Other studies have revealed defects in skeletal muscle even in absence of motor neuron anomalies, focusing on acetylcholine receptors (AChRs) and supporting the so-called "dying-back" hypothesis. Outcome of this study will be to understand if the endocannabinoid palmitoylethanolamide (PEA) can reduce the rundown of AChRs currents in ALS muscle, and if it can modify ALS patients' clinical and electrophysiological parameters.

Start Date01 Jan 2014

Sponsor / Collaborator

Sapienza University of Rome

100 Clinical Results associated with PPARα x CB2

100 Translational Medicine associated with PPARα x CB2

0 Patents (Medical) associated with PPARα x CB2

Literatures (Medical) associated with PPARα x CB2

01 Oct 2024·Metabolism

Cannabinoid receptor 2 plays a key role in renal fibrosis through inhibiting lipid metabolism in renal tubular cells

Article

Author: Li, Xiaolong ; Wang, Xiaoxu ; Liang, Ye ; Li, Zhiru ; Shen, Weiwei ; Kong, Yaozhong ; Li, Jiemei ; Hou, Fan Fan ; Zhang, Mengyao ; Wu, Qinyu ; Zhou, Shan ; Liu, Youhua ; Zhou, Lili ; Feng, Qijian ; Xie, Chao ; Chen, Qiyan ; Ling, Xian ; Miao, Jinhua

AIMSRenal fibrosis is a common feature in various chronic kidney diseases (CKD). Tubular cell damage is a main characterization which results from dysregulated fatty acid oxidation (FAO) and lipid accumulation. Cannabinoid Receptor 2 (CB2) contributes to renal fibrosis, however, its role in FAO dysregulation in tubular cells is not clarified. In this study, we found CB2 plays a detrimental role in lipid metabolism in tubular cells.METHODSCB2 knockout mice were adopted to establish a folic acid-induced nephropathy (FAN) model. CB2-induced FAO dysfunction, lipid deposition, and fibrogenesis were assessed in vivo and vitro. To explore molecular mechanisms, β-catenin inhibitors and peroxisome proliferator-activated receptor alpha (PPARα) activators were also used in CB2-overexpressed cells. The mediative role of β-catenin in CB2-inhibited PPARα and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) activation was analyzed.RESULTSCB2 activates β-catenin signaling, resulting in the suppression of PPARα/PGC-1α axis. This decreased FAO functions and led to lipid droplet formation in tubular cells. CB2 gene ablation effectively mitigated FAO dysfunction, lipid deposition and uremic toxins accumulation in FAN mice, consequently retarding renal fibrosis. Additionally, inhibition to β-catenin or PPARα activation could greatly inhibit lipid accumulation and fibrogenesis induced by CB2.CONCLUSIONSThis study highlights CB2 disrupts FAO in tubular cells through β-catenin activation and subsequent inhibition on PPARα/PGC-1α activity. Targeted inhibition on CB2 offers a perspective therapeutic strategy to fight against renal fibrosis.

01 Jul 2024·The Journal of Pain

Discovery and Preclinical Evaluation of a Novel Inhibitor of FABP5, ART26.12, Effective in Oxaliplatin-Induced Peripheral Neuropathy

Article

Author: Warren, George ; Yates, Andrew ; Osborn, Myles ; Bradshaw, Heather ; David-Pereira, Ana ; Kaczocha, Martin ; Duffy, Paul ; O'Sullivan, Saoirse E ; Ojima, Iwao ; Cohn, Daniel ; Tsantoulas, Christopher ; Ruston, Linette ; Johnson, Clare

Oxaliplatin-induced peripheral neuropathy (OIPN) is a dose-limiting toxicity characterised by mechanical allodynia and thermal hyperalgesia, without any licensed medications. ART26.12 is a fatty acid-binding protein (FABP) 5 inhibitor with antinociceptive properties, characterised here for the prevention and treatment of OIPN. ART26.12 binds selectively to FABP5 compared to FABP3, FABP4, and FABP7, with minimal off-target liabilities, high oral bioavailability, and a NOAEL of 1,000 mg/kg/day in rats and dogs. In an established preclinical OIPN model, acute oral dosing (25-100 mg/kg) showed a cannabinoid receptor type 1 (CB₁)-dependent anti-allodynic effect lasting up to 8 hours (persisting longer than plasma exposure to ART26.12). Antagonists of cannabinoid receptor type 2 (CB₂), peroxisome proliferator-activated receptor alpha, and transient receptor potential cation channel subfamily V member 1 (TRPV1) may have also been implicated. Twice daily oral dosing (25 mg/kg bis in die (BID) for 7 days) showed anti-allodynic effects in an established OIPN model without the development of tolerance. In a prevention paradigm, coadministration of ART26.12 (10 and 25 mg/kg BID for 15 days) with oxaliplatin prevented thermal hyperalgesia, mitigated mechanical allodynia, and attenuated OXA-induced weight loss. Multi-scale analyses revealed widespread lipid modulation, particularly among N-acyl amino acids in the spinal cord, including potential analgesic mediators. Additionally, ART26.12 administration led to upregulation of ion channels in the periaqueductal grey, and broad translational upregulation within the plasma proteome. These results show promise that ART26.12 is a safe and well-tolerated candidate for the treatment and prevention of OIPN through lipid modulation. PERSPECTIVE: Inhibition of fatty acid-binding protein 5 (FABP5) is a novel target for reducing pain associated with chemotherapy. ART26.12 is a safe and well-tolerated small molecule FABP5 inhibitor effective at preventing and reducing pain induced with oxaliplatin through lipid modulation and activation of cannabinoid receptors.

23 Mar 2023·International journal of molecular sciences

Beta-Caryophyllene Modifies Intracellular Lipid Composition in a Cell Model of Hepatic Steatosis by Acting through CB2 and PPAR Receptors.

Article

Author: Bonzano, Sara ; Scandiffio, Rosaria ; Cottone, Erika ; Shrestha, Sujata ; Maffei, Massimo E ; De Marchis, Silvia ; Bovolin, Patrizia ; Bossi, Simone

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease; however, no specific pharmacological therapy has yet been approved for this condition. Plant-derived extracts can be an important source for the development of new drugs. The aim of this study was to investigate the effects of (E)-β-caryophyllene (BCP), a phytocannabinoid recently found to be beneficial against metabolic diseases, on HepG2 steatotic hepatocytes. Using a fluorescence-based lipid quantification assay and GC-MS analysis, we show that BCP is able to decrease lipid accumulation in steatotic conditions and to change the typical steatotic lipid profile by primarily reducing saturated fatty acids. By employing specific antagonists, we demonstrate that BCP action is mediated by multiple receptors: CB2 cannabinoid receptor, peroxisome proliferator-activated receptor α (PPARα) and γ (PPARγ). Interestingly, BCP was able to counteract the increase in CB2 and the reduction in PPARα receptor expression observed in steatotic conditions. Moreover, through immunofluorescence and confocal microscopy, we demonstrate that CB2 receptors are mainly intracellularly localized and that BCP is internalized in HepG2 cells with a maximum peak at 2 h, suggesting a direct interaction with intracellular receptors. The results obtained with BCP in normal and steatotic hepatocytes encourage future applications in the treatment of NAFLD.

News (Medical) associated with PPARα x CB2

08 Aug 2022

·www.biospace.com

SciSparc Announces Israeli Ministry of Health Approval to Conduct its Clinical Trial in Autism Spectrum Disorder

The trial's objectives are to evaluate the safety, tolerability and efficacy of SciSparc's SCI-210 in children and adolescents with ASD TEL AVIV, Israel, Aug. 08, 2022 (GLOBE NEWSWIRE) -- SciSparc Ltd. (Nasdaq: SPRC) ("Company" or "SciSparc"), a specialty clinical-stage pharmaceutical company focusing on the development of therapies to treat disorders of the central nervous system, today announced that it has received approval from the Israeli Ministry of Health to conduct the Company’s clinical trial for SCI-210 in patients suffering from autism spectrum disorder ("ASD"). Recently, the Company announced it received approval from the Ethics Committee of The Soroka University Medical Center, in Be'er-Sheva, Israel, to conduct the Company’s clinical trial. “We are pleased to achieve another important milestone that brings us one step closer toward initiation of our clinical trial in ASD,” commented Oz Adler, SciSparc's Chief Executive Officer. "ASD symptoms in pediatric patients may cause a sever decrease in life quality, for parents and children. We believe that our unique and proprietary SCI-210 has the potential to be a new treatment to reduce irritability and other conditions associated with ASD. Patients today have limited treatment options while the need for such treatment rapidly grows. Our drug candidates potentially enable us to provide effective, safer and more tolerable treatment with fewer side effects thanks to the lower doses of cannabinoids, boosted by the combination with CannAmide™, a mission always desirable but even more so when children are the target population." The trial will investigate the effect of the Company’s drug candidate SCI-210, a proprietary combination of cannabidiol (“CBD”) and CannAmide™, versus CBD monotherapy in treating ASD. The trial's objectives are to evaluate the safety, tolerability and efficacy of SCI-210 in children and adolescents with ASD in a designed 20-week, randomized, double-blind, placebo controlled with a cross-over clinical trial of 60 children. The trial has three primary efficacy end points: the Aberrant Behavior Checklist-Community (ABC-C) parent questionnaire; the Clinical Global Impressions-Improvement (CGI-I) performed by a clinician; and the effective therapeutic dose. ASD is a condition related to brain development that impacts how a person perceives and socializes with others, causing problems in social interaction and communication. The term "spectrum" in autism spectrum disorder refers to the wide range of symptoms and severity. The launch of the trial is pending further approvals by the Israeli Medical Cannabis Agency. About SciSparc Ltd. (NASDAQ: SPRC): SciSparc Ltd. is a specialty clinical-stage pharmaceutical company led by an experienced team of senior executives and scientists. SciSparc’s focus is on creating and enhancing a portfolio of technologies and assets based on cannabinoid pharmaceuticals. With this focus, the Company is currently engaged in the following drug development programs based on THC and/or non-psychoactive cannabidiol (CBD): SCI-110 for the treatment of Tourette Syndrome, for the treatment of Alzheimer's disease and agitation; SCI-160 for the treatment of pain; and SCI-210 for the treatment of autism spectrum disorder and status epilepticus. Forward-Looking Statements: This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995 and other Federal securities laws. For example, SciSparc is using forward-looking statements when it discusses the initiation of the Company’s clinical trial in its drug candidate SCI-210 in patients suffering from ASD, the potential effect and evaluation of the drug candidate SCI-210 and further regulatory approvals in Israel to conduct its ASD research trial with The Soroka University Medical Center. Historic results of scientific research and clinical and preclinical trials do not guarantee that the conclusions of future research or trials will suggest identical or even similar conclusions. Because such statements deal with future events and are based on SciSparc's current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of SciSparc could differ materially from those described in or implied by the statements in this press release. The forward- looking statements contained or implied in this press release are subject to other risks and uncertainties, including those discussed under the heading "Risk Factors" in SciSparc's Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission (the “SEC”) on April 28, 2022, and in subsequent filings with the SEC. Except as otherwise required by law, SciSparc disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date they were made, whether as a result of new information, future events or circumstances or otherwise. Investor Contact: IR@scisparc.com Tel: +972-3-6167055

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