National ALS Biorepository Current Research
Studies approved for the use of National ALS Biorepository samples.
This list will be updated as new research proposals are approved by ATSDR.
|Study Name||Institution||Sample Type||Investigator||Date|
RNA-Sequencing based drug discovery in ALS
|Cerevance, Inc.||Serum, brain, spinal cord||Dr. Mark Carlton||Ongoing|
Assessment of Unbound Free Fatty Acids in ALS Plasma
|Center for Neurologic Study||Plasma||Richard Smith, MD||Ongoing|
Biomarkers in neuronal exosomes for assessment of ALS progression
|University of California Los Angeles (UCLA)||Serum||Gal Bitan, PhD||Ongoing|
|Novel extracellular vesicle and molecular biomarkers of environmental exposure and disease progression in ALS||Columbia University Medical Center||Brain tissue||Neil Shneider, MD, PhD||Ongoing|
|Metals analysis||Centers for Disease Control and Prevention (CDC)||Whole blood, serum, urine||National ALS Registry||Ongoing|
|Mitochondrial DNA and Micro RNAs in Amyotrophic Lateral Sclerosis||Columbia School of Public Health||Whole blood, plasma, brain and spinal cord||Pam Factor-Litvak, PhD||Ongoing|
|Role of FUS protein in inflammation and neurodegeneration, as potentially applied to understanding the development of ALS||Icahn School of Medicine at Mount Sinai/||Human primary cells||Ivan Marazzi, PhD||Ongoing|
|ALS risk, exposure sources, and effects on the unfolded protein response pathway||Dartmouth College||Fingernails||Elijah Stommel, MD PhD||Ongoing|
|Identification and characterization of potential environmental risk factors for ALS using the ATSDR ALS Registry cases and a control population.||University of Pittsburgh||Blood||Evelyn Talbott, DrPH||Ongoing|
|Targeting Ataxin-2 in Amyotrophic lateral sclerosis (ALS)||University of Utah||Human primary cells||Stefan M. Pulst, MD||Ongoing|
|Genotyping of Samples for the National ALS Biorepository||National Institutes of Health||DNA||Bryan Traynor, MD, PhD||Ongoing|
In ALS, two types of nerve cells which control movement are damaged: upper (cortical) and lower (spinal) motor neurons.
The aim of this research is to use technology to analyze gene sequences in very precise, isolated samples of both types of neurons. We believe that analyzing gene expression in healthy donors and those with ALS, will help us understand the fundamental changes seen in disease. It is also possible that some of genes which behave differently in neurons from ALS patients, may encode proteins which are suitable drug targets. In conducting this research, we would like to try and discover new drug targets for patients with ALS.
This research is trying to develop a biomarker that would be a reliable and measurable indicator of the severity of ALS. Free fatty acids are substances in the blood that are essential to the formation of more complex fats. They also involved in biological messaging. Only unbound free fatty acids, which make up a small fraction of all the fatty acids present in blood, are biologically active. Therefore, the measurements of total free fatty acids in blood should be insensitive to any changes in these unbound free fatty acid fractions and could be used as a biomarker for this disease.
This pilot study will measure biochemical changes in the blood serum of patients with ALS. These changes reflect the disease in their nervous system that causes their disability and paralysis. Specifically, we will measure certain biochemicals at two time points, at least 6 months apart and examine if they change significantly as the disease progresses.
- Novel extracellular vesicle and molecular biomarkers of environmental exposure and disease progression in ALS
The study from the Columbia University Health Sciences will test new non-invasive ways for identifying possible toxic exposures to the brains of ALS patients. The study will explain which processes link exposures and progression of disease. The study will be the first to test whether extracellular vesicles from the central nervous system can be used as new biomarkers. These biomarkers will be measures of environmental exposures and disease progression in ALS. The researchers will test samples from persons with ALS for metals and pesticides. They will then match the exposure and patient specific transcriptomic signatures to ALS signaling pathways.
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.
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.
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.
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.
Recent studies have explored the genetics of ALS. We only understand the genetics in 15% of ALS cases. DNA samples from the National ALS Biorepository will help these ongoing efforts. We will study the genetic makeup of the PALS who provided samples. Researchers will also be able to access these samples and data to advance the genetic understanding of ALS.