A-Z™ ALS Drug Discovery Platform

The platform developed by Creative Biolabs covers all compound-based detection needs and technologies. Over the past decade, our team has accumulated a wealth of project expertise. We can develop and validate custom assays for compounds to advance preclinical drug discovery.

Overview

Amyotrophic lateral sclerosis (ALS) is considered a complex multifactorial and genetic disorder characterized by protein aggregation, mitochondrial dysfunction, oxidative stress, and excitotoxicity, leading to motor neuron apoptosis. ALS is the most common neurodegenerative disorder in mid-life and amongst the most rapidly fatal, with death occurring nearly 2-3 years after symptom onset.

Creative Biolabs' ALS Drug Discovery Platform

ALS drug development has traditionally used cell culture and transgenic animal model systems to identify and pre-clinically test compounds. The most common transgenic animal models utilize overexpression of human SOD1.

ALS In Vitro Disease Models

Human induced pluripotent stem cells (hiPSCs) are a type of human pluripotent stem cells (hPSCs) that can be generated by the reprogramming of the somatic cells of an individual. hiPSCs and hESCs have represented powerful tools for studying human development, modeling diseases, performing drug screening campaigns, and evaluating the future of cell replacement therapy.

Fig.1 Human motor neurons generated from ALS patients have allowed disease mechanistic studies and in vitro drug screening campaigns.

ALS In Vivo Disease Models

Simple animal models of a disease may be used as tools for the therapeutic discovery of compounds that suppress the disease phenotype, regardless of the specific molecular targets. Using Creative Biolabs' platform, we screened worms expressing mutant ALS genes by video microscopy for the effects of these compounds on recovery of motility or survival.

• C. elegans

Its synaptic interconnections are well characterized, which makes it an ideal model to study cellular mechanisms of neurological disorders such as ALS. The first C. elegans ALS model was established by introducing human wild-type and ALS-related mutant forms (A4V, G37R, and G93A) of SOD1 under the control of a muscle promoter.

• Drosophila

The wealth of genetic tools for manipulating gene activity and neuronal function in Drosophila has made this simple organism a versatile model for studying disease mechanisms and for drug discovery. Several Drosophila models have been generated to study ALS pathogenesis. Overexpression of TDP-43 in motor neurons was found to cause cytoplasmic accumulation of TDP-43 aggregates, neuromuscular junction (NMJ) morphological defects, and cell death.

• Zebrafish

Zebrafish is a powerful organism for the study of vertebrate biology, physiology, and human disease. Overexpression of mutant but not wild-type human SOD1 in zebrafish leads to short motor axons. In addition to SOD1, models for the more recently identified ALS genes TARDBP, FUS, and C9ORF72 have also been developed, often first, in the zebrafish.

Creative Biolabs provides a proven and innovative one-stop pre-clinical drug discovery solution. We will find a way to manage the entire project to meet your needs. When working with us, there is no need to change providers, which can be time-consuming and expensive. You can rely on our skilled and enthusiastic staff to find the most appropriate path, and we can make your ALS preclinical drug discovery journey easier. Please feel free to contact us to discuss your project with our experts.