Washington, D.C. (December 2, 2015) — Results from two independent research groups on an important new mouse model of inherited ALS gene C9orf72 indicate that development of disease pathology precedes neurodegeneration, and can be reversed by therapies targeting the mutant gene responsible for the pathology. The studies were funded in part by The ALS Association.
In late September, The ALS Association convened leaders in ALS research for a three-day conference to discuss and collaborate on the most promising therapeutic developments: antisense oligonucleotides, gene therapy, and stem cell therapy. Researchers from across the country turned out for the conference, which was sponsored by The Greater New York Chapter and held at the Banbury Center at Cold Spring Harbor Laboratory in Huntington, New York. The event was a prime opportunity for these researchers to offer updates on their progress, some of which are described below.
Yes. You read that right. Veterans are twice as likely to be diagnosed with ALS as civilian counterparts. And scientists don’t yet understand why.
On Veteran’s Day, we’d like to take a moment to honor all those who served and share one of their stories with you.
The ALS Association is pleased to announce funding as a part of its Clinical Management Research Program, funding for a new study of young people who care for someone with ALS. The results of the study will be used to better understand the needs of youth caregivers and to design support services to address those needs.
While the proportion of families with a teen or child caring for a person with ALS is unknown, it is clear that many ALS families include youth who may assume caregiver roles. The new study, led by Melinda Kavanaugh, Ph.D., Assistant Professor of Social Welfare at the University of Wisconsin in Milwaukee, will collect data on ALS families nationwide and conduct interviews with youth caregivers to better understand their experiences.
“With no national data on the number of families who rely on young carers in ALS, it is difficult to develop appropriate and targeted support services and programs,” Dr. Kavanaugh said. “Thus, identifying why families rely on young carers and assessing their experience will not only provide relevant data for the development of support programs and services, but also lay the groundwork for a longitudinal understanding of how caregiving influences the lives of young carers.” A better understanding of these issues will also identify areas for improvement in the quality of life for the family as a whole.
“This important study will help The ALS Association better meet the needs of ALS families,” said Kimberly Harding-Maginnis., Chief Care Services Officer. “It is a recognition that the entire family, including its younger members are affected by the disease, and may benefit from the services The ALS Association can offer.”
Military Veterans are twice as likely to develop ALS as people who have not served. That’s why the Veteran Administration’s Hudson Valley Health Care System asked The ALS Association Greater New York Chapter to visit their Castle Point Campus in Wappingers Falls, NY recently to provide in-service training on caring for ALS patients.
Helen Mayer, RN and Nancy Brenner, LCSW, Patient Services Coordinators who manage the Greater New York Chapter’s service area that covers Westchester, Rockland and Lower Hudson Valley presented to over 30 staff members from the interdisciplinary team from the VA’s home based program including doctors, nurses, social workers, dietitians, nurse practitioners, and recreational therapists. The Wappinger Falls VA’s goal in requesting the inservice was to help them further their knowledge about veterans in their care who have ALS.
The Greater New York Chapter offers in service training on ALS at no cost to multidisciplinary teams treating patients with ALS at health care facilities such as Hospitals, Nursing Homes, Rehabilitation Centers, Home Care Agencies and Hospices. If you would like more information about our program or would like to request an in-service training, please contact Intake and Support Program Manager Tracy Sandy-Ali, LPN at (212) 720-3060 or firstname.lastname@example.org.
Two independent studies, both funded by The ALS Association, have found a genetic abnormality that, according to researchers, is the most common cause of Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). As reported in the recent online issue of the scientific journal Neuron, an unusual mutation was discovered, where a short DNA sequence is repeated many more times as compared to healthy individuals.
Using next generation sequencing in a study led by Bryan J. Traynor, M.D., Laboratory of Neurogenetics, National Institute on Aging, the team identified a GGGGCC hexanucleotide repeat within the non-coding region of a gene on chromosome 9p21. This repeat accounts for nearly 50% of familial ALS cases in Finland and more than a third of familial cases in other European populations.
The identification of the same genetic abnormality was independently made by a group at Mayo Clinic in Jacksonville, Florida led by Rosa Rademakers, Ph.D. and published in the same journal. The repeat of C and G (two of the four nucleotides that make up the genetic code) was found in a non-coding region of a gene called C9ORF72, which has no known function and its role in disease remains a mystery.
“We believe that when the defective gene is transcribed into a messenger RNA molecule, the expanded repeat section causes the RNA to bind tightly to certain proteins, forming clumps within the brain cells,” according to Dr. Rademakers. “By binding these proteins, the abnormal RNA may prevent these proteins from carrying out their normal functions in the cell.”
The identification of the genetic lesion on the chromosome 9p21 locus marks a major milestone in ALS research. Several studies have led to the identification of this region linked to chromosome 9p21 including recent genome-wide association (GWA) studies.
Investigators worldwide have been committed to identifying the gene alteration, and until now it had remained elusive. This hexanucleotide repeat was identified using state of the art next-generation sequencing technology. “The repeat expansion was highly associated with ALS and FTD in the Finnish population,” said Dr. Traynor.
“Since all routine methods of genetic analysis had failed to find the genetic defect in this region, we suspected the defect could be a rare DNA repeat expansion,” said lead investigator Mariely DeJesus-Hernandez from the Mayo Clinic-led research team. This team found an area of DNA that in healthy individuals is normally repeated only 2 to 23 times, but in ALS or FTD patients is repeated 700-1,600 times. These changes were found in almost 12 percent of familial FTD and more than 23 percent of familial ALS samples studied at Mayo Clinic.
The defect is also the strongest genetic risk factor found to date for the more common, non-inherited, sporadic forms of these diseases. It was found in 3 percent of sporadic FTD and 4 percent of sporadic ALS samples in Mayo Clinic’s large clinical patient series.
“This finding has the potential to lead to significant insights into how both of these neurodegenerative diseases develop, and may give us much needed leads into new ways to treat our patients,” said Senior Investigator Rosa Rademakers, a neuroscientist at the Mayo Clinic campus in Florida.
The repeat expansion is more than twice as common as the SOD1 gene in familial ALS and four times as common as TDP43, FUS, VCP combined. The identification of this repeat and the rapid, reliable method of screening individuals for repeat expansion may have immediate utility by allowing early identification of ALS patients at risk of cognitive impairment and FTD cases at risk of progressive paralysis.
In the long term, the identification of the genetic lesions underlying the chromosome 9p21 ALS-FTD together with the high frequency makes it an ideal target for drug development aimed at ameliorating the disease process. “Whether the pathogenic process is linked to a loss of function in which the expansion disrupts splicing of the target or through the generation of toxic RNA disrupting normal cellular processes will be determined by further study,” added Traynor. “However the large size of the expansion and its location in a non-coding region may argue for the later mechanism.”
Disruption of RNA metabolism has already been identified as an important mechanism in those cases with TDP43 and FUS mutations, and this discovery provides further evidence for disrupted RNA metabolism as a key underlying cause of disease.
“This is tremendously exciting,” commented ALS Association Chief Scientist Dr. Lucie Bruijn, Ph.D. “These findings will significantly impact the field as we begin to understand more about the consequence of these changes to the disease process, aid our understanding of FTD and ALS, potentially provide a diagnostic tool, and enable the development of new therapeutic approaches.”
Dr. Traynor’s team was funded by The ALS Association’s Abendroth ALS Genetic Discovery Fund, with additional funding from the Robert Packard Institute of ALS Research at Johns Hopkins. Dr. Rademakers’ team was funded by the The ALS Association’s Florida Chapter and Richard Essey. Both studies were funded by the National Institute on Aging and the National Institute on Neurological Diseases and Stroke.
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