The Larry G. Gluck Division of ALS Research, located at the Tisch MS Research Center of New York, has published research in Brain Communications identifying apolipoprotein B-100 (ApoB) as a key agent responsible for causing permanent motor disability, motor neuron degeneration, and other hallmark pathology in sporadic amyotrophic lateral sclerosis (sALS), a fatal neurodegenerative disease affecting 90% of ALS patients. Using an innovative experimental approach to deliver cerebrospinal fluid (CSF) from ALS patients, researchers developed a novel CSF-mediated mouse model to investigate pathophysiological mechanisms in different ALS subtypes.

In the study, researchers compared the neurotoxic capacity of CSF obtained from patients with sALS and those with the less prevalent familial ALS (fALS) with mutations in the SOD1, C9orf72, and TARDBP genes. Using the mouse model to detect motor impairments and pathological changes in the spinal cord, the researchers discovered that sALS CSF was neurotoxic but fALS CSF was not. Researchers refined the list of potential neurotoxic candidates by systematically filtering out components from sALS CSF by size, then reassessing neurotoxicity of the filtered CSF in mice. Global proteome profiling of CSF helped identify ApoB as the neurotoxic protein responsible for inducing motor disability and motor neuron degeneration. The researchers showed that targeted removal of ApoB from sALS CSF via filtration or immunodepletion prevented the process of motor neuron degeneration, possibly identifying a new treatment target for ALS patients.

“The impact of this research is potentially groundbreaking for patients with sporadic ALS, the predominant form of this devastating disease,” said Dr. Saud A. Sadiq, Director and Chief Research Scientist at the Tisch MS Research Center of New York. “For the first time ever, our novel animal model has identified the protein responsible for causing debilitating symptoms like motor disability and motor neuron degeneration in sALS. Targeted reduction of this protein from CSF could open up a new and potentially promising avenue to treat thousands of ALS patients.”

“We are excited to build upon the foundation established with this novel sALS animal model, as we now have the opportunity to further investigate sALS CSF-induced pathophysiological mechanisms and test potential therapies in a sALS-specific model,” added Tisch principal investigator and lead author, Dr. Jamie K. Wong. “Additionally, our team is using a CSF-induced animal model to investigate primary progressive multiple sclerosis, and this approach may potentially be useful for studying other neurodegenerative diseases as well.”

[Source(s): Tisch MS Research Center of New York, Business Wire]