Biorepository Description of Projects

The following are approved ALS research requests for specimens from the National ALS Biorepository.

This list will be updated as new research proposals are approved by ATSDR.

ALSStudiesClinicalTrails that have used
Study Name Institution Investigator Sample type(s)
Metals analysis Centers for Disease Control and Prevention (CDC) National ALS Registry Whole blood, serum, urine
Genomic analysis NIH/ATSDR Bryan Traynor, MD, PhD, MMSc, MRCPI DNA
Mitochondrial DNA and Micro RNAs in Amyotrophic Lateral Sclerosis Columbia School of Public Health Pam Factor-Litvak, PhD Whole blood, plasma, brain and spinal cord
Role of FUS protein in inflammation and neurodegeneration, as potentially applied to understanding the development of ALS Icahn School of Medicine at Mount Sinai/ Ivan Marazzi, PhD Human primary cells
ALS risk, exposure sources, and effects on the unfolded protein response pathway Dartmouth College Elijah Stommel, MD PhD Fingernails
Identification and characterization of potential environmental risk factors for ALS using the ATSDR ALS Registry cases and a control population. University of Pittsburgh Evelyn Talbott, DrPH Blood
Targeting Ataxin-2 in Amyotrophic lateral sclerosis (ALS) University of Utah Stefan M. Pulst, MD Human primary cells
  • Metals analysis

There have been limited studies that measured environmental chemicals in specimens from persons with ALS. We will first focus on metals and metalloids, including mercury, cadmium, lead, manganese, arsenic, chromium, selenium, copper, and possibly others. We will examine the hypothesis that exposure to metals is associated with the getting ALS. We will use specimens that were collected as part of the ALS biorepository. We expect the sample size will be between 300 and 600. The biorepository does not include a control group. Therefore, we will use the NHANES data to obtain estimates of the distribution of metal levels for the US Population.

  • Genomic analysis

DNA samples are evaluated for mutations in known ALS genes. The NeuroChip genotyping array is used. It is a low-cost, custom-designed array. It contains a tagging variant backbone of about 306,670 variants. 179,467 variants have been added. These added variants have been linked to diverse neurological diseases. These diseases include Alzheimer’s disease, Parkinson’s disease, Lewy body dementia, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy.

  • Mitochondrial DNA and Micro RNAs in Amyotrophic Lateral Sclerosis

Recent advances in the molecular genetics have increased understanding of many of the genetic/familial forms of ALS and other motor neuron diseases. Nevertheless, most ALS cases cannot be attributable to genes alone. There is much to be learned from studying environmental factors in the etiology and progression of ALS and other motor neuron diseases. Recent evidence points to a role of oxidative stress in the etiology of ALS. Recent developments in molecular epidemiology suggest that changes in mitochondrial DNA (mtDNA) and microRNAs (miRNAs) are associated with oxidative stress. The best biological specimens to measure these novel biomarkers would be the motor cortex of the brain and the spinal cord. However, these tissues are not available until after death. In this project we will compare measures of mtDNA and miRNAs in the motor cortex, spinal cord, and blood. This will help us see whether blood adequately reflects their amounts in target tissues.

  • Role of FUS protein in inflammation and neurodegeneration, as potentially applied to understanding the development of ALS

Several pathogenic mutations have been identified in the genome of ALS patients. Each mutation is associated with varied phenotypes. The researcher’s lab studies the function of the protein FUS. FUS has numerous variants associated with ALS. To address the cause-effect relationship between inflammation and neurodegeneration the researcher aims to study the function of FUS along with other ALS implicated proteins in the context of susceptibility to infection.

  • ALS risk, exposure sources, and effects on the unfolded protein response pathway

The first phase of the proposed study will focus on comparing exposures to environmental pollutants (lead, mercury, and other heavy metals) in nails. Samples from ALS patients will come from the National ALS Biorepository. They will compare with those of controls from a large, nationally representative prospective cohort. This cohort is funded by the National Institute of Environmental Health Sciences.

  • Identification and Characterization of Potential Environmental Risk Factors for ALS using the ATSDR ALS Registry Cases and a Control Population

This research will study self-reported environmental/occupational exposure to metals, pesticides, and solvents for persons with ALS and controls. It will also study life-time air pollution exposure based on where people lived. The first aim will look at a variety of air pollution data. The second aim will verify self-reported exposures to solvents and pesticides using blood measures of persistent pollutants. In aim three we will study the relationship between environmental toxicants in human samples and key biological pathways and common genes associated with developing ALS.

  • Targeting Ataxin-2 in Amyotrophic lateral sclerosis (ALS)

In 1996 we discovered a gene that is mutated in a rare disorder known as spinocerebellar ataxia type 2, or SCA2. The mutated gene that causes SCA2 is called ATXN2. When mutated ATXN2 gains abnormal and toxic functions. For diseases caused by such “gain of function disease genes,” it is believed that treatments that lower or eliminate their function may be therapeutic. Recent studies have shown that lowering the amount of ATXN2 also improves the survival of mice with the same abnormalities causing ALS in humans. The underlying reason for that is related to the abundance of yet another protein called staufen. Staufen is overabundant when ATXN2 is mutated. We have shown that lowering staufen works essentially as well as lowering ATXN2 for treating SCA2 mice. We also shown that staufen is overabundant in cells that are abnormal in ALS. Our hypothesis is that therapeutics that target the abundance of staufen will be as effective for treating ALS as therapeutics that target ATXN2. Moreover, targeting staufen may be an effective therapeutic approach for the treatment of other progressive neurological disorders. This research will support future work on the producing a drug that targets staufen for the treatment of ALS and potentially other neurological diseases.