The Miller Lab seeks to understand the mechanisms underlying neurodegeneration in ALS and to develop new, innovative therapies for ALS and other neurodegenerative diseases, such as Alzheimer’s disease.
What is ALS?
Amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, is a rapidly progressive, fatal neurodegenerative disease that leads to loss of neurons in the motor pathways of the brain and spinal cord. The average life space from diagnosis is two to five years. Currently, there are no adequate therapies.
Why do some misfolded proteins cause damage in ALS?
In many neurodegenerative diseases, including ALS, mutant (usually misfolded) proteins selectively damage the brain and spinal cord. One hypothesis for this occurrence is that the turnover (synthesis and degradation) of the mutant protein is less efficient in the central nervous system compared to other tissue types. To address this hypothesis, the Miller Lab is using a variety of biochemical techniques in cell culture, mouse models, and humans to understand how protein turnover of mutant superoxide dismutase 1 (SOD1) influences motor neuron-specific degeneration in ALS. Mutations in SOD1 are responsible for approximately 10-20% of inherited ALS and may also be implicated in sporadic ALS.
Is it safe to target SOD1 in humans with ALS?
The ability to target and “turn off” genes using oligonucleotide based strategies (RNAi and antisense oligonucleotides) has been a huge step forward in understanding a wide variety of biological processes. These tools also offer a great opportunity to develop gene targeted therapies for the central nervous system. By knocking down SOD1 with antisense oligonucleotides delivered to the cerebral spinal fluid that bathes the brain and spinal cord, we extended survival in animal models of ALS. This novel therapy for inherited ALS is currently being tested in an ongoing human Phase I/II trial. More information about this trial can be found here.