Patrick Haslett

Protection from malaria infection using liver-targeted siRNA

Ryan Steel, Antonino Schepis, Thao Nguyen, Stuart Milstein et autres

infection using human liver-chimeric mice. The data suggest siRNA as a promising host-based approach to prevent malaria infection.

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Evaluation of RNAi therapeutics VIR-2218 and ALN-HBV for chronic hepatitis B: Results from randomized clinical trials

Ed Gane, Young‐Suk Lim, Jae Bum Kim, Vasant Jadhav et autres

BACKGROUND & AIMS: Current therapy for chronic hepatitis B virus (cHBV) infection involves lifelong treatment. New treatments that enable HBV functional cure would represent a clinically meaningful advance. ALN-HBV and VIR-2218 are investigational RNA interference therapeutics that target all major HBV transcripts. …

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From bench to bedside: Improving the clinical safety of GalNAc–siRNA conjugates using seed-pairing destabilization

Mark K. Schlegel, Maja M. Janas, Yongfeng Jiang, Joseph D. Barry et autres

Preclinical mechanistic studies have pointed towards RNA interference-mediated off-target effects as a major driver of hepatotoxicity for GalNAc-siRNA conjugates. Here, we demonstrate that a single glycol nucleic acid or 2'-5'-RNA modification can substantially reduce small interfering RNA (siRNA) seed-mediated binding to off-target …

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GWAS of serum ALT and AST reveals an association of SLC30A10 Thr95Ile with hypermanganesemia symptoms

Lucas D. Ward, Ho-Chou Tu, Chelsea B. Quenneville, Alexander O. Flynn-Carroll et autres

Understanding mechanisms of hepatocellular damage may lead to new treatments for liver disease, and genome-wide association studies (GWAS) of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum activities have proven useful for investigating liver biology. Here we report 100 loci associating with …

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Phase 1/2 Study of Lumasiran for Treatment of Primary Hyperoxaluria Type 1

Yaacov Frishberg, Georges Deschênes, Jaap W. Groothoff, Sally‐Anne Hulton et autres

BACKGROUND AND OBJECTIVES: In the rare disease primary hyperoxaluria type 1, overproduction of oxalate by the liver causes kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. Lumasiran, an RNA interference therapeutic, suppresses glycolate oxidase, reducing hepatic oxalate production. The objective of this …

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RNA Interference Targeting Liver Angiopoietin-Like Protein 3 Protects from Nephrotic Syndrome in a Rat Model Via Amelioration of Pathologic Hypertriglyceridemia

Yitong Zhao, Masaki Goto, Nosratola D. Vaziri, Mahyar Khazaeli et autres

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Activation of Protein Kinase A (PKA) signaling mitigates congenital hyperinsulinism associated hypoglycemia in the Sur1-/- mouse model

Mangala M. Soundarapandian, Christine A. Juliana, Jinghua Chai, Patrick Haslett et autres

There is a significant unmet need for a safe and effective therapy for the treatment of children with congenital hyperinsulinism. We hypothesized that amplification of the glucagon signaling pathway could ameliorate hyperinsulinism associated hypoglycemia. In order to test this we evaluated the …

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GWAS of serum ALT and AST reveals an association of SLC30A10 Thr95Ile with hypermanganesemia symptoms

Lucas D. Ward, Ho-Chou Tu, Chelsea B. Quenneville, Shira Tsour et autres

Abstract To investigate mechanisms of hepatocellular damage, we performed genome-wide association studies (GWAS) on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum activities across 411,048 subjects from four ancestry groups in the UK Biobank, and found 100 loci associating with both enzymes. …

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Increased Plasma Levels of the TH2 chemokine CCL18 associated with low CD4+ T cell counts in HIV-1-infected Patients with a Suppressed Viral Load

Prashant Malhotra, Patrick Haslett, Barbara Sherry, David H. Shepp et autres

The chemokine (C-C motif) chemokine ligand 18 (CCL18) is a structural homolog of CCL3 primarily produced by monocyte-derived cells with an M2 phenotype. Elevated levels of CCL18 have been observed in several diseases associated with malignancies and chronic inflammation. The role of …

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MP12-14 SAFETY AND EFFICACY STUDY OF LUMASIRAN, AN INVESTIGATIONAL RNA INTERFERENCE (RNAI) THERAPEUTIC, IN ADULT AND PEDIATRIC PATIENTS WITH PRIMARY HYPEROXALURIA TYPE 1 (PH1)

Yaacov Frishberg, Georges Deschênes, Pierre Cochat, Daniella Magen et autres

You have accessJournal of UrologyStone Disease: Medical & Dietary Therapy (MP12)1 Apr 2019MP12-14 SAFETY AND EFFICACY STUDY OF LUMASIRAN, AN INVESTIGATIONAL RNA INTERFERENCE (RNAI) THERAPEUTIC, IN ADULT AND PEDIATRIC PATIENTS WITH PRIMARY HYPEROXALURIA TYPE 1 (PH1) Yaacov Frishberg, Georges Deschenes, Pierre Cochat, …

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Improving Drug Discovery by Nucleic Acid Delivery in Engineered Human Microlivers

Liliana Mâncio-Silva, Heather E. Fleming, A. B. Miller, Stuart Milstein et autres

The liver plays a central role in metabolism; however, xenobiotic metabolism variations between human hepatocytes and those in model organisms create challenges in establishing functional test beds to detect the potential drug toxicity and efficacy of candidate small molecules. In the emerging …

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Observational Prospective Natural History of Patients with Sanfilippo Syndrome Type B

Chester B. Whitley, Maureen Cleary, Eugen Mengel, Paul Harmatz et autres

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