enzyme replacement therapeutics / Washington University School of Medicine in St. Louis, UT Southwestern Medical Center, Collaborations Pharma - LARVOL DELTA

The Prevalence of Low Fecal Elastase Among Patients With Pancreatic Adenocarcinoma (ACG 2024) - "Pancreatic enzyme replacement therapy was used by 78.8% of patients... Among the 66 PDAC patients, 49 (74.2%) had fecal elastase 200 μg/g. Mean age at diagnosis was 64.8 years, with females accounting for 51.5% of the study sample. About 91% of study participants were White."

Clinical • Diabetes • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Metabolic Disorders • Oncology • Pain • Pancreatic Adenocarcinoma • Pancreatic Cancer

Preliminary Safety Data of a Phase 1/2 Clinical Trial to Support the Use of High Dose Intrathecal AAV9/AP4M1 for the Treatment of Patients with SPG50 Disease (ASGCT 2024) - "APM41 treatment is challenging as it does not benefit from cross correction or amenable to enzyme replacement therapy...No deleterious immune responses have been noted, and the treatment has been tolerated well across all 4 subjects. There has been no evidence of dorsal root ganglia toxicity and nerve conduction has been shown to be stable following gene transfer."

Clinical • P1/2 data • CNS Disorders • Developmental Disorders • Epilepsy • Gene Therapies • Genetic Disorders

Combining angiotensin receptor blockade and enzyme replacement therapy for vascular disease in mucopolysaccharidosis type I. (PubMed, Mol Genet Metab Rep) - "Vascular involvement in the genetic disorder mucopolysaccharidosis type I (MPS I) has features of atherosclerotic disease near branch points of arterial vasculature, such as intimal thickening with disruption of the internal elastic lamina, and proliferation of macrophages and myofibroblasts. Some cytokines, notably CD30 ligand, Eotaxin-2, LIX, IL-13, IL-15, GM-CSF, MCP-5, MIG, and CCL3 showed elevations in mice treated with ERT above normal or mutant levels; these elevations were reduced or absent in mice that received losartan or combination therapy. The observations suggest that losartan may impact inflammatory cascades due to MPS I and may also blunt inflammation in combination with ERT."

Journal • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Genetic Disorders • Hurler Syndrome • Inflammation • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases • CCL3 • CSF2 • IL13 • IL15 • ITGB2 • TGFB1 • TNFRSF8 • TNFSF8

Association of In-Line Digestive Enzyme Cartridge With Enteral Feeds on Anthropometrics Among Pediatric Patients With Cystic Fibrosis (ACG 2023) - "Pancreatic enzyme replacement therapy (PERT) can be taken with meals to ameliorate this issue... Weight, height, and BMI z-score changed over time based on multivariable longitudinal regression models after adjusting for relevant variables identified a priori, including age at start of ILC, sex, PERT dose with GT feeds prior to ILC, PERT with GT feeds after starting ILC, and CF gene mutations. Compared to mean height z-score at 6-months-before-ILC, mean height z-score at 6-months-after-ILC (adjusted mean difference=0.2540; 95% CI=[0.0487, 0.4592]; p=0.0153) and mean height z-score at 12-months-after-Relizorb (adjusted mean difference = 0.2684; 95% CI=[0.0203, 0.5166]; p=0.0340) were significantly higher. Mean weight z-score at 12-months-after-ILC neared statistical significance when compared to 6-months-before-ILC (adjusted mean difference=0.2816; 95% CI=[-0.0003, 0.5634]; p=0.0502) when excluding 7 patients with the most advanced lung disease (FEV1 < 50)."

Clinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pediatrics • Pulmonary Disease • Respiratory Diseases

Cross-species efficacy of enzyme replacement therapy for CLN1 disease in mice and sheep. (PubMed, J Clin Invest) - "These findings demonstrate the feasibility and therapeutic efficacy of intracerebroventricular rhPPT1 enzyme replacement therapy. This represents a key step towards clinical testing of ERT in children with CLN1 disease and highlights the importance of a cross-species approach to developing a successful treatment strategy."

Journal • Preclinical • CNS Disorders • Gene Therapies • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Advancing the Research and Development of Enzyme Replacement Therapies for Lysosomal Storage Diseases. (PubMed, GEN Biotechnol) - "There may still be considerable scientific and investment potential for ERT, however we need to develop a pipeline of proteins analogous to what has been created in some open science efforts as well as apply technologies to decrease manufacturing costs. In this Perspective, we illustrate the opportunity to fill the rare LSD treatment gap with ERTs while gene therapies are in development for these life-shortening diseases."

Journal • Gene Therapies • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Biochemical evaluation of intracerebroventricular rhNAGLU-IGF2 enzyme replacement therapy in neonatal mice with Sanfilippo B syndrome. (PubMed, Mol Genet Metab) - "The overall therapeutic effects of single dose ICV-ERT with rhNAGLU-IGF2 in Naglu neonatal mice were long-lasting. These results suggest a potential benefit of early treatment, followed by less-frequent ICV-ERT dosing, in patients diagnosed with MPS IIIB."

Journal • Preclinical • IGF2