Nucleic Acid Aptamer Selection against Superoxide Dismutase 1 for the Treatment of Amyotrophic Lateral Sclerosis

Elizabeth Adams 9/2/13

Nucleic Acid Aptamer Selection against Superoxide Dismutase 1 for the Treatment of Amyotrophic Lateral Sclerosis

Superoxide Dismutase 1 (SOD1) is a soluble protein, found primarily in the cytoplasm of cells, that converts harmful superoxide radicals to oxygen and hydrogen peroxide [1]. Recent research advances have found that the mutant form of SOD1 plays an active role in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS), or Lou Gehrig’s disease [1]. ALS is a neurodegenerative disorder that causes the death of motor neurons in the brain and spinal cord, eventually leading to fatal paralysis in 2 to 5 years (see Figure 1) [2,3,4].  More specifically, it is the first known causative gene responsible for the familial form of ALS [3]. Some evidence even shows that mutations within the exons of the gene that codes for SOD1 contribute to the onset of sporadic ALS, which makes up 90% of ALS cases [1,2].

An aptamer, an RNA strand that binds with high affinity, can be found for SOD1 to develop treatments for both familial and sporadic ALS cases. It is also believed that the accumulation of SOD1 in sites directly affected by the disease, like the spinal cord and brain stem, further progresses the degeneration of nerve cells [1,5]. An aptamer could be used to detect this elevated level, and also, by some mechanism, inhibit the harmful accumulation of SOD1.

The mutant form of SOD1 only directly causes 2% of ALS cases worldwide, so a more important goal would be to develop a treatment based off this knowledge that could be effective in treating all the other cases of ALS [1]. Researchers are continually learning more about ALS, but much is left unknown. An aptamer effective in treating ALS cases associated with the mutation of SOD1 could be the breakthrough to creating a world without ALS.

Specific Aims:

The selection of RNA aptamers against SOD1 could be used to develop treatments to halt the devastating effects of Amyotrophic Lateral Sclerosis. Also, by inhibiting the accumulation of SOD1 that has known to exacerbate the disease, treatments can be developed. Treatment developed based on an aptamer for SOD1, to treat ALS cases caused by the mutation of SOD1 could be used and modified to develop treatments, later on, for sporadic ALS cases in which the specific cause is still unknown.

Figure 1: Figure 1, taken from the Yale Medical Group website, depicts a normal nerve cell compared to a nerve cell affected by amyotrophic lateral sclerosis. The nerve cell that has been affected by ALS is weak, shriveled, and ultimately prevents the muscle from being stimulated properly, which causes the muscle to degenerate over time [4]. An aptamer which halts the destruction of the nerve cell would limit the damage to the muscle.

Ordering Information: 

Superoxide Dismutase Protein (His Tag) (MW=16.8 kDa) can be ordered from Sino Biological, Inc.
Catalog Number: 11727-H07E
Cost for 100ug = $200
Cost per Round = $6.72

References:

[1] Milani P, Gagliardi S, Cova E, Cereda C. “SOD1 transcriptional and posttranscriptional regulation and its potential implications in ALS.” Neurology Research International, 2011. Web. 30 Aug. 2013.

[2] "Genetics of ALS." Alsa.org. The ALS Association, n.d. Web. 30 Aug. 2013.

[3] "Recombinant Human SOD1 / Superoxide." Sinobiological.org. Sino Biological, Inc, n.d. Web. 30 Aug. 2013.

[4] "Amyotrophic Lateral Sclerosis (ALS)." Yalemedicalgroup.org. Yale School of Medicine, 2013. Web. 30 Aug. 2013.

[5] "Laboratory Models of ALS." Alsa.org. The ALS Association, n.d. Web. 30 Aug. 2013.

View Full Target Proposal: https://docs.google.com/file/d/0B9sjx3wzW_h4Q2xyTDZSZENtYnM/edit?usp=sharing

View Progress Report 1: https://docs.google.com/file/d/0B9sjx3wzW_h4SjNZY3l4S3VlUWc/edit?usp=sharing

View Progress Report 2: https://drive.google.com/file/d/0B9sjx3wzW_h4cGtLNTRmZzY1TVk/edit?usp=sharing

View Final Report: https://drive.google.com/file/d/0B9sjx3wzW_h4R0JSMkJodTlfUXc/edit?usp=sharing