This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison, Spring 2012.
ALS in the Primary Literature:
Exendin-4 Ameliorates Motor Neuron Degeneration in Cellular and Animal Models of
Amyotrophic Lateral Sclerosis.
Li et al. 2012
Amyotrophic Lateral Sclerosis.
Li et al. 2012
Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of motor neurons, leading to loss of motor control. There are currently no treatments that can reverse this degeneration, and only one FDA-approved drug that can slow the progression of the disease. Therefore, much of research today focuses on finding a cure, slowing disease progression, or making patients more comfortable. This research includes a variety of clinical trials on ALS patients, including drug and stem cell therapies. But before any treatment can be tested on humans, it must first undergo extensive testing on model organisms.
Recent work by a group of scientists led by Yazhou Li at the National Institute on Aging at the National Institutes of Health (NIH) describes their attempt to utilize a therapeutic currently used to treat diabetes in slowing the progression of ALS using cell culture and mice models. The therapeutic drug, Exendin-4 (Ex-4), stimulates a hormone receptor found in pancreatic cells and leads to insulin secretion, making it a useful tool in treating type 2 diabetes. These critical hormone receptors are also present on neurons in the central nervous system, and Ex-4 treatment has been shown to protect these neurons from oxidative stress and some forms of cell death, both of which occur in the neurons of patients suffering from ALS. When mice with mutations in SOD1, which display ALS-like symptoms, are treated with Ex-4, the death of their neurons is lessened and they perform better on a running wheel test than untreated mice.
While the researchers admit that these experiments do not necessarily indicate that Ex-4 would successfully treat ALS in humans, these early experiments suggest that Ex-4 should be further evaluated as a possible therapeutic, first continuing in mice models and later potentially in clinical trials. Ex-4 is an ideal candidate for a therapeutic, as it has already been shown to be tolerated by humans for use in treating diabetes. With further study of its neuroprotective properties in both animal models and humans, Ex-4 may be shown to be a useful therapeutic in patients with a number of different neurodegenerative diseases including Parkinson's and Alzheimer's in addition to ALS.
To read the full article, click here.
Recent work by a group of scientists led by Yazhou Li at the National Institute on Aging at the National Institutes of Health (NIH) describes their attempt to utilize a therapeutic currently used to treat diabetes in slowing the progression of ALS using cell culture and mice models. The therapeutic drug, Exendin-4 (Ex-4), stimulates a hormone receptor found in pancreatic cells and leads to insulin secretion, making it a useful tool in treating type 2 diabetes. These critical hormone receptors are also present on neurons in the central nervous system, and Ex-4 treatment has been shown to protect these neurons from oxidative stress and some forms of cell death, both of which occur in the neurons of patients suffering from ALS. When mice with mutations in SOD1, which display ALS-like symptoms, are treated with Ex-4, the death of their neurons is lessened and they perform better on a running wheel test than untreated mice.
While the researchers admit that these experiments do not necessarily indicate that Ex-4 would successfully treat ALS in humans, these early experiments suggest that Ex-4 should be further evaluated as a possible therapeutic, first continuing in mice models and later potentially in clinical trials. Ex-4 is an ideal candidate for a therapeutic, as it has already been shown to be tolerated by humans for use in treating diabetes. With further study of its neuroprotective properties in both animal models and humans, Ex-4 may be shown to be a useful therapeutic in patients with a number of different neurodegenerative diseases including Parkinson's and Alzheimer's in addition to ALS.
To read the full article, click here.
1. Li Y, Chigurupati S, Holloway HW, Mughal M, Tweedie D, Bruestle DA, Mattson MP, Wang Y, Harvey BK, Ray B, Lahiri DK, Greig NH. (2012). Exendin-4 ameliorates motor neuron degeneration in cellular and animal models of amyotrophic lateral sclerosis. PLoS One 7 (2): e32008. PMID:22384126