Engineering protein-based therapeutics through structural and chemical design

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Апрель 27, 2023

Protein-based therapeutics have led to new paradigms in disease treatment. Projected be half of the top ten selling drugs 2023, proteins emerged as rivaling and, some cases, superior alternatives historically used small molecule-based medicines. This review chronicles both well-established and emerging design strategies that enabled this paradigm shift by transforming protein-based structures are often prone denaturation, degradation, aggregation vitro vivo into highly effective therapeutics. In particular, we discuss for creating with increased affinity targetability, enhanced stability pharmacokinetics, improved cell permeability, reduced amounts undesired immunogenicity.

Язык: Английский

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Utility of genetic risk scores in type 1 diabetes

Diabetologia, Год журнала: 2023, Номер 66(9), С. 1589 - 1600

Опубликована: Июль 13, 2023

Iterative advances in understanding of the genetics type 1 diabetes have identified >70 genetic regions associated with risk disease, including strong associations across HLA class II region that account for >50% heritability. The increased availability data combined decreased costs generating these data, facilitated development polygenic scores aggregate variants from loci into a single number: either score (GRS) or (PRS). PRSs incorporate many possibly correlated genome, even if they do not reach genome-wide significance, whereas GRSs estimate cumulative contribution smaller subset significance. Type utility classification, aiding discrimination between diabetes, 2 and MODY. are also being used newborn screening studies to identify infants at future presentation disease. Most early been conducted European ancestry populations, but, develop accurate diverse ancestries, large case-control cohorts non-European populations still needed. current barriers GRS implementation within healthcare mainly related lack guidance knowledge on integration other biomarkers clinical variables. Once limitations addressed, there is huge potential 'test treat' approaches be tailor care individuals diabetes.

Язык: Английский

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The effect of GLP-1R agonists on the medical triad of obesity, diabetes, and cancer

Cancer and Metastasis Reviews, Год журнала: 2024, Номер 43(4), С. 1297 - 1314

Опубликована: Май 27, 2024

Glucagon-like peptide-1 receptor (GLP-1R) agonists have garnered significant attention for their therapeutic potential in addressing the interconnected health challenges of diabetes, obesity, and cancer. The role GLP-1R type 2 diabetes mellitus (T2DM) is highlighted, emphasizing its pivotal contribution to glucose homeostasis, promoting β-cell proliferation, facilitating insulin release. effectively managed obesity by reducing hunger, moderating food intake, regulating body weight. Beyond exhibit a multifaceted impact on cancer progression across various malignancies. mechanisms underlying these effects involve modulation signaling pathways associated with cell growth, survival, metabolism. However, current literature reveals lack vivo studies specific such as semaglutide, necessitating further research elucidate precise effects, particularly While other shown promising outcomes mitigating progression, association between some an increased risk remains topic requiring more profound investigation. This calls extensive unravel intricate relationships agonist different cancers, providing valuable insights clinicians researchers alike.

Язык: Английский

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Familial aggregation and heritability of childhood-onset and adult-onset type 1 diabetes: a Swedish register-based cohort study

The Lancet Diabetes & Endocrinology, Год журнала: 2024, Номер 12(5), С. 320 - 329

Опубликована: Март 29, 2024

Язык: Английский

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IFN-α neutralizing antibodies distinguish LADA from early-onset type 1 diabetes

The Journal of Clinical Endocrinology & Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Янв. 6, 2025

Autoantibodies against IFN-α (AAb-IFN-α) might be associated with the less aggressive autoimmunity in latent autoimmune diabetes adults (LADA) compared to early-onset type 1 (T1D).

Язык: Английский

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Type 1 Diabetes Is Not Just a Pediatric Problem

Clinical Diabetes, Год журнала: 2025, Номер 43(1), С. 4 - 4

Опубликована: Янв. 1, 2025

Язык: Английский

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The diagnosis of LADA diabetes in a low-resource country: A Peruvian case series

Electronic Journal of General Medicine, Год журнала: 2025, Номер 22(4), С. em653 - em653

Опубликована: Апрель 30, 2025

<b>Introduction:</b> Diabetes mellitus (DM) is a global public health concern, affecting 10% of adults. Among its variants, latent autoimmune diabetes in adults (LADA) accounts for 3% to 11% cases. Limited awareness and high testing costs contribute misdiagnosis inadequate treatment, increasing the risk chronic complications.<br /> <b>Design:</b> A cases series.<br <b>Methods:</b> Fifteen Peruvian patients with LADA were studied describe their clinical presentation, diagnosis, treatment.<br <b>Results:</b> The average age was 36.2 years, mean disease duration 5.6 years. All presented acute symptoms, body mass index at diagnosis 23.3 kg/m². Glycemic control achieved an daily insulin dose 0.96 IU/kg. None had access capillary glucose self-monitoring or continuous monitoring, as all living poverty extreme poverty.<br <b>Conclusions:</b> uncommon form early-onset DM whose treatment resource-limited countries are impacted by socioeconomic conditions. Therefore, we propose algorithm managing this condition low-resource settings.

Язык: Английский

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Immune checkpoint modulators in early clinical development for the treatment of type 1 diabetes

Expert Opinion on Investigational Drugs, Год журнала: 2024, Номер 33(4), С. 303 - 318

Опубликована: Март 1, 2024

Introduction Despite the improvements of insulin therapy, people with type 1 diabetes (T1D) still suffer from a decreased quality life and expectancy. The search toward cure for T1D is therefore scorching open field research.

Язык: Английский

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Obesity in type 1 diabetes: an overlooked immune-metabolic issue

Expert Review of Endocrinology & Metabolism, Год журнала: 2024, Номер 19(4), С. 295 - 297

Опубликована: Май 3, 2024

Язык: Английский

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Latent autoimmune diabetes in adults: current data (review of literature and own data)

INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), Год журнала: 2024, Номер 20(3), С. 163 - 172

Опубликована: Июнь 27, 2024

The article provides up-to-date information on latent autoimmune diabetes in adults (LADA), presents data epidemiology, factors and mechanisms of development, clinical features this disease. phenotypic variants the course LADA are described, issues diagnostic differential diagnosis revealed. is a form characterized by less intense process wide range signs compared to classical type 1 mellitus (T1DM) can have both major types diabetes. Based results epidemiological studies, prevalence approximately 12 % all cases diabetes, it second most common after 2 (T2DM) adults. According modern classification, belongs subtype T1DM. Since patients do not need insulin at beginning disease, similar T2DM, which cause errors. literature conducted research shown that, addition damage pancreatic beta cells, resistance plays key role with an increase frequency degree abdominal obesity, only worsens metabolic control increases risk syndrome, but also causes decrease secretion progression process. In LADA, hypertension dyslipidemia occupy intermediate position between Despite having fewer same or even higher death cardiovascular diseases. important markers levels C-peptide autoantibodies against islet antigens. possibility clear limited due significant heterogeneity disease overlap T1DM T2DM symptoms. guidelines, therapeutic approaches based therapy metformin, depend level C-peptide. More needed improve personalized treatment

Язык: Английский

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