Amyotrophic
Lateral Sclerosis or ALS is a neurodegenerative disorder that results in weaker
voluntary muscles, and the failure of motor neurons. The majority of patients
with the disease do not survive more than 3 years because of respiratory
failure. A major question that researchers have faced since the discovery of
the disorder concerns the origin of the disease. Early on, there was thought to
only be an environmental susceptibility factor for the disease, but in the 1950’s,
a case study determined that there was indeed a genetic component to the
disease.
More
recently, with increasing advances in genetics, it has been shown that there
are at least 17 genes that are known to account for 70% of all cases of family
ALS, as well as many other genes that can promote limited susceptibility to the
disease (Chalabi & Hardman, 2013). This is an incredible advance in modern
genetics, because now we can locate specific genes that can increase risk
factors and susceptibility for the disease, and hopefully educate people that
are trying to conceive a child on the probability of offspring contracting ALS.
This is a big step from believing that the disease only had environmental risk factors,
because researchers are now able to view how these factors can affect the expressivity
of certain genes. This is a similar concept to twin studies viewing obesity,
and how differences in diet can actually activate genes causing obesity in one
twin but not in the other. So far there have been links between smoking, exercise,
heavy metal exposure, cyanotoxins and more environmental factors.
Although,
many discoveries have been made about ALS, there are still many factors unknown
about the disease. Some links between the environment and genes have been made,
but it is often difficult to make some of these generalizations because of the
complex and infinite nature if the exposome (all physical experiences of an individual
through a lifetime). Even with these difficulties however, strides are being
made to better understand the disease. The more we learn about the epidemiology
helps providers make better calls for their patients when trying to alleviate
symptoms. Eventually, further knowledge could possibly lead to a cure for ALS,
highlighting the importance of further research.
Chalabi, A. A., &
Hardiman, O. (2013). The epidemiology of ALS: a conspiracy of genes,
environment and time. Nature Reviews Neurology, 9(11), 617+. Retrieved from
http://link.galegroup.com.dml.regis.edu/apps/doc/A351948309/AONE?u=regis&sid=AONE&xid=cc6906f4
Interesting post, I am wondering what the environmental risk factors are and how they relate to the expression of the disease. Is it possible that instead of a gene by environment interaction it is an epigenetic factor as well where maybe DNA methylation of the genes involved is causing the expression of the disease. If that's the case I wonder if using epigenetic medication therapy would work for ALS as it is in some cancers. I know they are now able to use epigenetic therapy for acute myeloid Leukemia (Griffiths et al., 2013), so if it were and epigenetic factor maybe these therapies could work as well.
ReplyDeleteGriffiths, E. A., & Gore, S. D. (2013). Epigenetic Therapies in MDS and AML. Advances in Experimental Medicine and Biology, 754, 253–283. http://doi.org.dml.regis.edu/10.1007/978-1-4419-9967-2_13
I definitely agree that there needs to be more variety in the epidemiological studies for ALS. It seems that there could be an issue of under reporting and under-representation. As such a complicated and debilitating disease, I really hope we make more advancements in finding a cure. However, I found another study that also highlighted metabolic pathways that impact ALS.
ReplyDeleteThe study mentions that some ALS related genes such as TARDBP have roles in regulating glucose and fatty acid metabolism. A deficit in these pathways could affect the physiopathology of ALS patients during exercise and other physical therapeutic functions. So not only do genes and the environment play a role in ALS, it seems our metabolic pathways also have some effect.
Zufiria, M., Gil-Bea, F. J., Fernandez-Torron, R., Poza, J. J., Muñoz-Blanco, J. L., Rojas-Garcia, R., ... & de Munain, A. L. (2016). ALS: a bucket of genes, environment, metabolism and unknown ingredients. Progress in neurobiology, 142, 104-129.
Roberts, A. L., Johnson, N. J., Chen, J. T., Cudkowicz, M. E., & Weisskopf, M. G. (2016). Race/ethnicity, socioeconomic status, and ALS mortality in the United States. Neurology, 10-1212.