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)

开始日期2023-09-01

申办/合作机构

SciSparc Ltd.

NCT05766969 / Unknown status临床1/2期

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.

开始日期2023-06-05

申办/合作机构

Pure Green Pharmaceuticals, Inc.

NCT02645461 / CompletedN/AIIT

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.

开始日期2014-01-01

申办/合作机构

Sapienza University of Rome

100 项与 PPARα x CB1 相关的临床结果

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100 项与 PPARα x CB1 相关的转化医学

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0 项与 PPARα x CB1 相关的专利（医药）

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项与 PPARα x CB1 相关的文献（医药）

2024-07-01·The Journal of Pain

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

Article

作者: 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.

2024-05-10·ACS Pharmacology & Translational Science

Hydroxytyrosol Linoleoyl Ether Ameliorates Metabolic-Associated Fatty Liver Disease Symptoms in Obese Zucker Rats

Article

作者: Rodríguez-Pozo, Miguel ; Baixeras, Elena ; de la Torre, Rafael ; Boronat, Anna ; Vargas, Antonio ; de Ceglia, Marialuisa ; de Fonseca, Fernando Rodríguez ; Tovar, Rubén ; Decara, Juan ; Suárez, Juan ; Gavito, Ana

A main hepatic consequence of obesity is metabolic-associated fatty liver disease (MAFLD), currently treated by improving eating habits and administrating fibrates yet often yielding suboptimal outcomes. Searching for a new therapeutic approach, we aimed to evaluate the efficacy of hydroxytyrosol linoleoyl ether (HTLE), a dual Ppar-α agonist/Cb1 antagonist with inherent antioxidant properties, as an antisteatotic agent. Using lean and obese Zucker rats, they were administrated daily doses of HTLE (3 mg/kg) over a 15-day period, evaluating its safety profile, pharmacokinetics, impact on body weight, hepatic fat content, expression of key enzymes involved in lipogenesis/fatty acid oxidation, and antioxidant capacity. HTLE decreased the body weight and food intake in both rat genotypes. Biochemical analysis demonstrated a favorable safety profile for HTLE along with decreased concentrations of urea, total cholesterol, and aspartate aminotransferase AST transaminases in plasma. Notably, HTLE exhibited potent antisteatotic effects in obese rats, evidenced by a decrease in liver fat content and downregulation of lipogenesis-related enzymes, alongside increased expression of proteins controlling lipid oxidation. Moreover, HTLE successfully counteracted the redox imbalance associated with MAFLD in obese rats, attenuating lipid peroxidation and replenishing both glutathione levels and the overall antioxidant. Our findings highlight the effectiveness of triple-action strategies in managing MAFLD effectively. Based on our results in the Zucker rat model, HTLE emerges as a promising candidate with triple functionality as an anorexigenic, antisteatotic, and antioxidant agent, offering potential relief from MAFLD symptoms associated with obesity while exhibiting minimal side effects. In conclusion, our study positions HTLE as a highly promising compound for therapeutic intervention in MAFLD treatment, warranting further exploration in clinical trials.

2023-11-01·Food Research International

Dry heat whole Sorghum BRS 305 flour modulate satiety and improves antioxidant response in brain of Wistar rats fed with high-fat high-fructose diet

Article

作者: Guedes Lúcio, Haira ; Maria Brunoro Costa, Neuza ; Beserra de Menezes, Cícero ; David Medina Martinez, Oscar ; Stampini Duarte Martino, Hércia ; Aparecida Vieira Queiroz, Valéria ; Celi Lopes Toledo, Renata ; Pereira da Silva, Bárbara ; Grancieri, Mariana

Sorghum BRS 305 (Sorghum bicolor L. Moench) is a cereal with high tannins and anthocyanins content and keep better the resistant starch when submitted to dry heat treatment. Our objective was to investigate the effects of BRS 305 dry heat treatment whole sorghum flour on satiety and antioxidant response in brain and adipose tissue of Wistar rats fed with a high fat high fructose diet (HFHF). Male Wistar rats were divided in two groups: control (n = 8) and HFHF (n = 16) for eight weeks. After, animals of HFHF group were divided: HFHF (n = 8) and HFHF + BRS 305 sorghum whole flour (n = 8), for 10 weeks. Sorghum consumption reduced gene expression of leptin, resistin, and endocannabinoid receptor 1 type (CB1) in adipose and brain tissues compared to HFHF group. In brain, sorghum consumption also promotes reduction in neuropeptide Y (NPY) gene expression. BRS305 sorghum consumption improved gene expression of sirtuin-1 (SIRT1) in adipose tissue, and in the brain increased heat shock protein 72 (HSP72), erythroid-derived nuclear factor 2 (NRF2), peroxisome proliferator-activated receptor alpha (PPARα), superoxide dismutase (SOD) and catalase activity compared to HFHF. In silicoanalysis showed interaction with PPARα, CB1, and leptin receptors. Advanced glycation end products (AGEs) concentrations in group HFHF + sorghum did not differ from HFHF group. Advanced glycation end products receptors (RAGEs) concentrations did not differ among experimental groups. Then, BRS 305 sorghum submitted to dry treatment was able to modulate gene expression of markers related to satiety and improve antioxidant capacity of rats fed with HFHF diet.

项与 PPARα x CB1 相关的新闻（医药）

2022-08-08

·BioSpace

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