Prominent publications by Alex M DePaoli

KOL Index score: 13315

BACKGROUND: Non-alcoholic steatohepatitis is a chronic liver disease characterised by the presence of hepatic steatosis, inflammation, and hepatocellular injury, for which no Food and Drug Administration (FDA)-approved treatment exists. FGF19 is a hormone that regulates bile acid synthesis and glucose homoeostasis. We aimed to assess the safety and efficacy of NGM282, an engineered FGF19 analogue, for the treatment of non-alcoholic steatohepatitis.

METHODS: In this randomised, ...

Also Ranks for: Alcoholic Steatohepatitis |  2 trial |  liver fat content |  hepatic steatosis |  aged double
KOL Index score: 13274

The safety and bone antiresorptive effect of a single subcutaneous dose of AMG 162, a human monoclonal antibody to RANKL, was investigated in 49 postmenopausal women. AMG 162 is a potent antiresorptive agent for diseases such as osteoporosis.

INTRODUCTION: RANKL is an essential osteoclastic differentiation and activation factor.

MATERIALS AND METHODS: The bone antiresorptive activity and safety of AMG 162, a fully human monoclonal antibody to RANKL, were evaluated in postmenopausal women ...

Also Ranks for: Postmenopausal Women |  amg 162 |  human monoclonal |  6 months |  bone turnover osteoporosis
KOL Index score: 13130

BACKGROUND: NGM282, an engineered analogue of the gut hormone FGF19, improves hepatic steatosis and fibrosis biomarkers in patients with non-alcoholic steatohepatitis (NASH). However, NGM282 increases serum cholesterol levels by inhibiting CYP7A1, which encodes the rate-limiting enzyme in the conversion of cholesterol to bile acids. Herein, we investigate whether administration of a statin can manage the cholesterol increase seen in patients with NASH receiving treatment with ...

Also Ranks for: Ngm282 Patients |  alcoholic steatohepatitis |  fgf19 analogue |  baseline week |  fat content
KOL Index score: 13119

BACKGROUND & AIMS: The degree of cholestasis is an important disease driver in alcoholic hepatitis, a severe clinical condition that needs new biomarkers and targeted therapies. We aimed to identify the largely unknown mechanisms and biomarkers linked to cholestasis in alcoholic hepatitis.

METHODS: Herein, we analyzed a well characterized cohort of patients with alcoholic hepatitis and correlated clinical and histological parameters and outcomes with serum bile acids and fibroblast ...

Also Ranks for: Alcoholic Hepatitis |  bile acids |  new biomarkers |  serum fgf19 |  fibroblast growth factor
KOL Index score: 12520

BACKGROUND: Lack of leptin is implicated in insulin resistance and other metabolic abnormalities in generalized lipodystrophy; however, the efficacy, safety, and underlying mechanisms of leptin-replacement therapy in patients with generalized lipodystrophy remain unclear.

METHODS: Seven Japanese patients with generalized lipodystrophy, two acquired and five congenital type, were treated with the physiological replacement dose of recombinant leptin during an initial 4-month ...

Also Ranks for: Generalized Lipodystrophy |  replacement therapy |  efficacy safety |  insulin resistance |  fatty liver
KOL Index score: 12019

BACKGROUND & AIMS: Aldafermin, an engineered analog of fibroblast growth factor 19, inhibits bile acid synthesis and regulates metabolic homeostasis. We report results from a 24-week, phase 2 study, with serial liver biopsies, of patients with nonalcoholic steatohepatitis (NASH).

METHODS: We performed a double-blind study of 78 patients with NASH at 9 centers in the United States. Key inclusion criteria were biopsy-proven NASH with Nonalcoholic Fatty Liver Disease Activity Score ≥4, ...

Also Ranks for: Nonalcoholic Steatohepatitis |  patients nash |  fibrosis improvement |  metabolic homeostasis |  liver fat
KOL Index score: 11520

Leptin is important in regulating energy homeostasis. Severe lipodystrophy is associated with leptin deficiency and insulin resistance, hypertriglyceridemia, and hepatic steatosis. Leptin deficiency is also associated with abnormalities of the pituitary hormones in rodent models and patients with congenital absence of leptin. We inquired whether similar abnormalities are seen in patients with lipodystrophy and whether replacement of leptin will make an impact on the regulation of ...

Also Ranks for: Leptin Replacement |  severe lipodystrophy |  4 months |  insulin resistance |  energy homeostasis
KOL Index score: 11466

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is an inflammatory, cholestatic and progressively fibrotic liver disease devoid of effective medical intervention. NGM282, an engineered, non-tumorigenic FGF19 analogue, potently regulates CYP7A1-mediated bile acid homeostasis. We assessed the activity and safety of NGM282 in patients with PSC.

METHODS: In this double-blind, placebo-controlled phase II trial, 62 patients who had PSC confirmed by cholangiography or biopsy and an ...

Also Ranks for: Primary Sclerosing Cholangitis |  fgf19 analogue |  patients psc |  12 weeks |  liver fibrosis
KOL Index score: 11027

NGM282, an engineered fibroblast growth factor 19 analogue, rapidly and significantly reduced liver fat content in a multicenter, randomized, double-blind, placebo-controlled study in patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH). However, it is unclear whether these changes would be accompanied by histological improvement. In this open-label study, we assessed the histological efficacy of NGM282 in patients with biopsy-confirmed nonalcoholic steatohepatitis. Paired ...

Also Ranks for: Liver Fibrosis |  nonalcoholic steatohepatitis |  12 weeks |  1 3 |  patients nash
KOL Index score: 10993

Alcoholic liver disease (ALD) is associated with changes in the intestinal microbiota. Functional consequences of alcohol-associated dysbiosis are largely unknown. The aim of this study was to identify a mechanism of how changes in the intestinal microbiota contribute to ALD. Metagenomic sequencing of intestinal contents demonstrated that chronic ethanol feeding in mice is associated with an over-representation of bacterial genomic DNA encoding choloylglycine hydrolase, which ...

Also Ranks for: Alcoholic Liver Disease |  intestinal bile |  fibroblast growth |  ald mice |  lipid metabolism
KOL Index score: 10786

To investigate the regulation of leptin secretion and pulsatility by fat mass, we performed overnight leptin sampling every 20 min for 12 h and compared leptin dynamics with total body and regional fat measurements in 20 healthy male subjects. Simultaneous growth hormone (GH), cortisol, and insulin levels were assessed to determine relatedness and synchronicity during overnight fasting. Deconvolution analyses were performed to determine simultaneous hormonal dynamics, synchronicity, and ...

Also Ranks for: Leptin Insulin |  gh cortisol |  growth hormone |  pulse dynamics |  fat mass
KOL Index score: 10550

BACKGROUND & AIMS: Bile acid nuclear receptor farnesoid X receptor (FXR) is a key molecular mediator of many metabolic processes, including the regulation of bile acid, lipid and glucose homeostasis. A significant component of FXR-mediated events essential to its biological activity is attributed to induction of the enteric endocrine hormone fibroblast growth factor (FGF)19 or its rodent ortholog, FGF15. In this report, we compared the properties of human FGF19 and murine FGF15 in the ...

Also Ranks for: Bile Acid |  human fgf19 |  mouse models |  knockout mice |  liver neoplasms
KOL Index score: 10491

Genetic mutations in the leptin pathway can be a cause of human obesity. It is still unknown whether leptin can be effective in the treatment of fully established morbid obesity and its endocrine and metabolic consequences in adults. To test the hypothesis that leptin has a key role in metabolic and endocrine regulation in adults, we examined the effects of human leptin replacement in the only three adults identified to date who have genetically based leptin deficiency. We treated these ...

Also Ranks for: Diabetes Mellitus |  leptin replacement |  morbid obesity |  deficient adults |  18 months
KOL Index score: 10433

CONTEXT: Leptin deficiency is associated with dyslipidemia and insulin resistance in animals and humans with lipoatrophy; leptin replacement ameliorates these abnormalities.

OBJECTIVE: The objective of the study was to evaluate the effects of leptin therapy in lipoatrophic HIV-infected patients with dyslipidemia and hypoleptinemia.

DESIGN: This was a 6-month, open-label, proof-of-principle pilot study.

SETTING: Metabolic ward studies were performed before and 3 and 6 months after leptin ...

Also Ranks for: Insulin Resistance |  visceral fat |  recombinant human leptin |  immunodeficiency virus |  patients hiv
KOL Index score: 10389

BACKGROUND: Disruptions in hypothalamic-gonadal and other endocrine axes due to energy deficits are associated with low levels of the adipocyte-secreted hormone leptin and may result in hypothalamic amenorrhea. We hypothesized that exogenous recombinant leptin replacement would improve reproductive and neuroendocrine function in women with hypothalamic amenorrhea.

METHODS: Eight women with hypothalamic amenorrhea due to strenuous exercise or low weight were studied for one month before ...

Also Ranks for: Hypothalamic Amenorrhea |  recombinant human leptin |  hormone levels |  low weight |  lh pulsatility

Key People For Leptin Replacement

Top KOLs in the world
Alex * *******
leptin replacement alcoholic hepatitis generalized lipodystrophy
Stephen * ** *******
insulin resistance type 2 diabetes food intake
Anthony * ******
leptin replacement severe lipodystrophy morbid obesity
Christos ******** *********
insulin resistance leptin levels metabolic syndrome
Ismaa ***** *******
human obesity food intake blood pressure
Jeffrey ******* ********
adipose tissue leptin receptor gene expression

Alex M DePaoli:Expert Impact

Concepts for whichAlex M DePaolihas direct influence:Leptin replacement,  Alcoholic hepatitis,  Generalized lipodystrophy,  Recombinant human leptin,  Severe lipodystrophy,  Nonalcoholic steatohepatitis,  Recombinant leptin,  Hypothalamic amenorrhea.

Alex M DePaoli:KOL impact

Concepts related to the work of other authors for whichfor which Alex M DePaoli has influence:Insulin resistance,  Adipose tissue,  Metabolic syndrome,  Leptin levels,  Liver disease,  Type 2 diabetes,  Anorexia nervosa.



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