Amyotrophic lateral sclerosis is a neurodegenerative disease in which the motor neurons of the brain and spinal cord progressively die. As these cells are required for movement, speech, breathing and swallowing the disease impacts on all of these functions with death usually occurring within three years after symptoms arise. Riluzole is the only drug currently available for ALS treatment and its effects are extremely limited. Thyrotropin releasing hormone (TRH) and its analogues have been shown to have neuroprotective effects in neuronal cell cultures . This project aims to explore the effects of TRH on fibroblasts from ALS patients and healthy controls. The cells will be grown in culture and treated with TRH and TRH analogues. The effect of TRH on susceptibility of cells to oxidative stress (shown to be increased in ALS patient fibroblasts) will be tested to investigate mechanisms underlying TRH’s beneficial effects. The effect of TRH will then be tested in human cortical neurons. These cells are developed from induced pluripotent stems cells (human fibroblasts which were converted back to their undifferentiated state) which can be guided to differentiate into desired cell types through regulation of their environment. Little work has been done in cortical neuron cultures to study human ALS. The study of TRH’s beneficial effects in cortical neurons can then be applied to improving therapeutics in ALS and related diseases.
