The Fruits of the Ice Bucket Challenge and A.L.S

          Were you one of the 17 million people who partook in the famous Ice Bucket challenge? Well if you did, you should be glad to know that you helped to raise not only awareness for Amyotrophic Lateral Sclerosis but, you also helped to raise over 115 million dollars for research into ALS otherwise known as Lou Gehrig’s disease. Very recently, researchers have been able to discover a gene that accounts for 3 percent of ALS cases known as NEK1. About 1 million dollars from the Ice Bucket Challenge was invested into a project known as Project MinE consisting of 11 countries and about 80 researchers. These researchers in turn were able to discover the NEK1 gene’s connection to the development of ALS.

            The NEK1 gene was discovered through the whole-exome analysis of over 1,000 individuals afflicted with familial ALS. The NEK1 gene discovered by researchers is very important to the nervous system. NEK1 is important in the maintenance of the cytoskeleton that gives neurons its shape and its ability to promote transportation within the neuron cells. NEK1 also has a big role in regulation of the mitochondria’s membrane. Other functions that NEK1 is associated with include cilia formation, DNA damage response, and microtubule stability. Once there is a problem in these functions due to the NEK1 gene being disabled or damaged, there is an increased chance for the development of ALS. Thankfully, now that NEK1 has been determined to be a gene of interest in regards to treating ALS, drug therapies can now be researched in targeting the NEK1 gene.

            To me, I'm glad to see that something that was a viral sensation throughout the world was able to do some good in discovering genes linked to ALS. I definitely believe that more good things are to come with this research not only in discovering more genes but also through social media in ways to help fund other researcher for other diseases. Although 30 genes have been discovered to have association with the cause of ALS, finding more and more genes related to it can help broaden treatment plans for those afflicted with ALS.

(http://www.nytimes.com/2016/07/28/health/the-ice-bucket-challenge-helped-scientists-discover-a-new-gene-tied-to-als.html?rref=collection%2Fsectioncollection%2Fhealth&action=click&contentCollection=health&region=stream&module=stream_unit&version=search&contentPlacement=10&pgtype=sectionfront)

ALS associated genes are the primary suspect that has a direct correlation to Lou Gehrig’s disease

It was thought that genetics’ played a small to no role in causing Amyotrophic lateralsclerosis (ALS), which is commonly referred to Lou Gehrig’s disease. A disease that affects the motor neuron by slowly killing them and slowing down their functions until it comes to a complete stop. This process will stop the signals that come from the brain to the muscle and will lead to the person being paralysis. 

This image is of the nerve cells comparison of a healthy and ALS affected nerve.

The researchers at Cedars-Sinai Medical center are looking into the genes that affect ALS, although this disease can occur to people who do not even have the disease in their bloodline. Even though it not in a person family genetic history, the researches discovered that this certain gene could be responsible for over a third of the people with Lou Gehrig’s disease. Through their studies they stated, “they found that patients with defects in two or more ALS-associated genes saw the onset of the disease approximately 10 years earlier than patients with single-gene mutations.” Meaning that this gene is promising to have a direct correlation with the degenerations of the motor neurons when there is at least two mutations.  Now that they narrow there search to theses genes they can think of the best way to fix the gene, through gene therapy, to help cure or improves the persons health.

I believe that these advancements in the study of the human genes will help find other unknown genes that could also cause Lou Gehrig’s in the near future.  

First article: http://www.news-medical.net/news/20141206/Genetics-may-play-major-role-in-Lou-Gehrigs-disease-study-reveals.aspx

Second article:http://losangeles.cbslocal.com/2014/12/05/study-genetics-may-play-larger-role-in-who-develops-als/

ALS gene discovery

HealthDay reporter Robert Preidt from US News writes Scientists Make Gene Discovery in Lou Gehrig's Disease to bring insight on the discovery of a gene mutation that is in cohorts with ALS, which is amyotrophic lateral sclerosis and also known as Lou Gehrig's disease. The U.S National Institute on Aging (NIA) performed the study and found this gene mutation. ALS is described as a deadly disease that wipes out the nerve cells which leads to paralysis and weakness. Usually people with this disease die from respiratory failure and according to the NIA, around 10% of the people that have this disorder have inherited ALS in some way or form. The study includes them researching each family's DNA that has multiple family members that have ALS. Results showed that several people within the family had a mutation on the Matrin 3 gene. This gene connects to a protein that attaches to RNA and this mutation generates ALS. Dr.Bryan Traynor says that the discovery gives them something to research more precisely on and also that the neuron death in ALS is somehow related to the disturbance of RNA metabolism. ALS causes 6,000 deaths in America each year.


I hope that the more they research the Matrin 3 gene, the closer they will get to finding a cure to prevent the disruption in RNA metabolism that'll lead to ALS. Since researchers have discovered the gene and now they know it's a gene that one can somewhat inherit, they can inform people ahead of time and possibly prevent them from passing it on to their children. I'm glad that researchers are cracking down genetically on these types of diseases and understanding them more so that they can prevent it or find a cure someday. 

To learn more about ALS click here: http://www.alsa.org/about-als/what-is-als.html
To read the original article: http://health.usnews.com/health-news/articles/2014/04/01/scientists-make-gene-discovery-in-lou-gehrigs-disease

3-D Changes in DNA May Lead to a Genetic Form of Lou Gehrig's Disease

A new discovery by Jiou Wang, Ph.D., and his colleagues at Johns Hopkins University that a mutation in the C9orf72 gene can cause neurodegeneration, or altering the shape of DNA which, in turn, kills the DNA molecule. Mutations in this C9orf72 gene causes amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), as well as frontotemporal degeneration (FTD). They also believe this mutation might be associated with Alzheimer's and Huntington's disease. In a normal C9orf72 gene, the nucleotide sequence repeats between 2-25 times, however, the mutation causes the gene to repeat tens of thousands of times. With these extra repetitions, the shape of the DNA molecules changes from the twisted ladder to G-quadruplexes (image below), which are stacks of square-shaped molecules called G-quartets. This mutation has serious effects on how the genetic message is processed. The mutated DNA forms a DNA-RNA hybrid structure called R-loops. The R-loops and G-quadruplexes disrupt the transcription process, thus patients with this mutation produce short transcripts. The cell functions abnormally because of these short transcripts. Dr. Wang also determined that this mutation effects the nucleolus which contains the cell's DNA and is the site for initial protein assembly. Dr. Wang teamed up with Jeffery D. Rothstein, M.D., also from Johns Hopkins University to observe the effects of the C9orf72 mutation on nucleolin which is a key protein inside the nucleolus. Their research show that the short transcripts bound to the nucleolin has toxic effects on the cell. In a healthy cell, the nucleolin is only present in a certain area of the nucleus, while in the cells from the ALS patients, nucleolin is present throughout the nucleus. They hypothesize that abnormal distribution of nucleolin kills the cell and results in ALS and FTD.

(The above image shows a G-quadruplex configuration)
I find this new discovery very important because now we know what happens on the molecular scale for ALS and FTD to occur. Scientist can now do experiments on how to stop this phenomenon from happening. This discovery also puts the foot in the door for a cure for Alzheimer's and Huntington's disease. This could be the start for some incredible discoveries in the future regarding ALS, FTD, Alzheimer's and Huntington's disease.

New Genetic Risk Factor for ALS

Amyotophic lateral sclerosis, also referred to as Lou Gehrig's diseasde is a disease in which there is progressive degeneration of the motor cells in the spinal cord and brain.  The degeneration inhibits nerve impulses from reaching muscles and the person will soon experience muscle weakness and eventually deterioration.  There is no known cure for ALS.  In recent studies biologists and neuroscientists have been ablidene to locate and identify a  new genetic risk factor.  They found evidence that mutations in the ataxin 2 gene were a genetic contributor to the disease.  The study showed that expansions of a run of the amino acid, glutamine, in ataxin 2 were associated with an increase risk for ALS, a frequency of 4.6% for all ALS cases studied.  Since there is no cure, only treatments that slow progression this new information combined with known information about the relationship of TDP-43 to ALS may be able to offer new types of therapy to slow the disease even further.
The experiment was first carried out on yeast genes and studying TDP-43.  They then began studying on fruit flies, confirming the results they had with yeast and showing that ataxin 2 was a potent modifier of TDP-43.  The higher the levels of ataxin 2, the higher the level of toxicity was in the fruit fly.  Ataxin 2 has been related to other spinal cord diseases and it is now apparent that the more ataxin 2 glutamine repeated stretches a person has, the greater their risk for ALS.


A role for the polyQ protein ataxin 2 in ALS was identified using yeast (top left), fruit fly models (top middle), human ALS motor neurons (top right) and genetic analysis in ALS patients (above). (Credit: University of Pennsylvania)