ALS - Part 5 - On Going Research

Gene Therapy

One of the developments that will assist research into ALS is a genome-wide map of the spinal cord. The Allen Spinal Cord Atlas contains around 18,000 genes in the spinal cord. This will assist scientists to understand the disease mechanisms involved with ALS (The ALS Association).

Although genomic research has been abundantly funded in the past decade, the result of this research has been limited but promising. The goal of researchers in ALS genomic sequencing is to find the genes that are involved in developing ALS and then develop treatments based on that knowledge (Al-Chalabi). For example, the mutation of a gene named SOD-1 (copper/zinc superoxide dismutase) is thought to be responsible for 2 to 7% of ALS cases. Discovery of a gene called TDP-43 (producing a protein TDP-43 or Tar DNA-Binding protein) which impacts a more common form of the disease has been found in the more recent past (Al-Chalabi). Determining how the gene mutation causes disease has been a goal of the ALS researchers along with using that information to mitigate or halt the disease process.

A recent development has been the creation of genetically engineered mice and rats that can reveal how TDP-43 may impact the development of ALS (Petrucelli). Having animal models will allow researchers to test various hypothesis as well as testing drugs to determine potential effectiveness. In healthy people, TDP-43 resides in the neuron’s nucleus. In people with ALS, the protein accumulates in the cytoplasm and forms inclusions (abnormal structures) (Petrucelli). The researchers now have to resolve if the aggregated proteins are toxic, just a by-product, or if the cells are using the formation as a protective mechanism to try to sequester a toxin (Petrucelli). The research on any genetic mutation, even though the gene is identified, still needs to reveal its secrets in how the mutation causes disease.

This paper is in honor of Warren Schaeffer, an exceptional
person, adventurous being and a first-class gentleman.