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ALS Hyperexcitation Model
Imaging ALS iPSC Cells
Biomarker Assays
Hyperexcitation is a well-recognized clinical symptom in amyotrophic lateral sclerosis. Hyperexcitatan is an early clinical symptom of amyotrophic lateral sclerosis. Fasciculation of muscles is caused by a hyperexcitation of neurons in the motor cortex. In neuronal cell cultures, hyperexcitation is connected with a shift in the so-called E/I balance, which is a shift in excitation inhibition homeostasis that can cause excitotoxicity. The exact mechanisms behind hyperexcitation in ALS, such as the involvement of TDP-43 dysfunction or Neurofilament Light Chains at neuronal axonal initial segments, are still being studied.
A distrubed E/I balance is closely connected with a disfunctional energy metabolism. A complementary study of hyperexcitation and dysfunctional energy metabolism supports confidence in your drug projects.
Our Approach
We have pioneered optimized protocols for MEA recordings to study human iPSC-derived spinal motor neurons with familial mutations such as SOD1, C9orf72, and TDP-43. We showed in all these diseased cell lines hyperexcitated activity patterns in MEA-recordings arising at different days in vitro of cultivation. Our hyperexcitation ALS models are functional phenotypic models with constructed, face, and predictive validity, providing valuable insights into ALS pathology..
Example of a SOD1 Mutation with Hyperexcitation Activity
Image: Spike train parameter comparison of a SOD1-D90A cell line, its isogenic control, and a C9orf72 cell line, demonstrating a highly hyper-excited activity pattern of the ALS mutated cell lines.
A potential ALS treatment should prevent hyperexcitation for a longer period in culture.
Example of a Therapeutic Intervention for Mitigating Hyperexcitation
Image: Spike train parameter comparison of a SOD1-D90A cell line, its isogenic control, and the treated SOD1-D90A cell line with riluzole, which shows a reduction in the hyperexcited activity pattern.
Screening Services
NeuroProof offers comprehensive screening services tailored to ALS drug development, encompassing various application schemes and all ALS cell lines.
NeuroProof is continuously expanding its assay portfolio, asking us for potential new ALS cell lines with familial or sporadic forms and co-cultures with astrocytes and/or microglia. Our expertise allows for customizable and optimized assays to meet the diverse needs of ALS researchers worldwide.
Collaboration and Innovation
We are committed to advancing ALS research through collaboration and innovation. As we continuously expand our assay portfolio, we invite researchers to partner with us in exploring new ALS cell lines, including familial and sporadic forms, as well as co-cultures with astrocytes or microglia. From sourcing diseased cell lines to compound screening campaigns, we offer integrated solutions to accelerate ALS drug discovery.
Contact Us
For further information on our ALS hyperexcitation model and screening services, please contact us. Together, let's make strides in understanding and combating ALS.