Title

The Pre-familial ALS (Pre-fALS) Study

Short name

Pre-fALS

Principal Investigator

Michael Benatar, MD, PhD

Site-PI

Summary

This is a longitudinal study of people who are at risk for developing familial ALS, with the specific goal of improving our understanding of the pre-symptomatic phase of fALS. Participants in this study have the option of whether or not to learn the results of genetic testing. Study participants travel to the University of Miami (paid for by the study) on an annual basis, at which time they undergo a number of study procedures (MRI, physiology, interview about environmental risk factors, collection of blood and urine samples, etc.). We also contact study participants quarterly by telephone to enquire whether any new symptoms have developed that may suggest the onset of ALS.

Eligibility criteria

• Age ≥ 18 years
  
• Member of a family in which at least two relatives have been affected with ALS
  
• Genetic mutation in the SOD1, TDP-43, FUS, or other fALS gene in a family member
  
• Currently no symptoms to suggest the presence of ALS
  
• Willingness to undergo genetic testing with the option of whether or not to learn the results
  
• Willingness to travel to Emory annually for in-person study evaluations

Funding agency

Muscular Dystrophy Association
Emory Woodruff Health Sciences Center

Collaborators

Pre-fALS: Genetics

Peter Andersen, MD, DMSc (Umea University, Sweden)
Clement Furlong, PhD (University of Washington)
Christine Stanislaw, MS (Emory University)
Bryan Traynor, MD, MRCPI, MSc (National Institute for Aging, NIH)

Pre-fALS: Epidemiology

Dana Barr, PhD (Centers for Disease Control and Prevention)
Lorene Nelson, PhD (Stanford University)
Rosemary Schleicher, PhD (Centers for Disease Control and Prevention)

Pre-fALS: Psychosocial

Joanna Fanos, PhD (Dartmouth Medical School)

Pre-fALS & Arimoclomol: Data Management

Roger Selsov (Massachusetts General Hospital Neurology Clinical Trials Unit)
Alex Sherman (PharmaContent, Inc., Massachusetts General Hospital Neurology Clinical Trials Unit)

Research Coordinator

Eliana Reyes, B.A.
Catalina Maria Fernandez, MD.

Contact information

Email:
Phone: 1-888-413-9315

Link(s)

http://clinicaltrials.gov/ct2/show/NCT00317616?term=Benatar&rank=4

http://www.mda.org/research/atlanta-emoryu-525k.html

http://mdadev.mda.org/research/gaag/2010/benatar

Publications

Renton AE, Majounie E, Waite A, Simón-Sánchez J, Rollinson S, Gibbs JR, Schymick JC, Laaksovirta H, van Swieten JC, Myllykangas L, Kalimo H, Paetau A, Abramzon Y, Remes AM, Kaganovich A, Scholz SW, Duckworth J, Ding J, Harmer DW, Hernandez DG, Johnson JO, Mok K, Ryten M, Trabzuni D, Guerreiro RJ, Orrell RW, Neal J, Murray A, Pearson J, Jansen IE, Sondervan D, Seelaar H, Blake D, Young K, Halliwell N, Callister JB, Toulson G, Richardson A, Gerhard A, Snowden J, Mann D, Neary D, Nalls MA, Peuralinna T, Jansson L, Isoviita VM, Kaivorinne AL, Hölttä-Vuori M, Ikonen E, Sulkava R, Benatar M, Wuu J, Chiò A, Restagno G, Borghero G, Sabatelli M; The ITALSGEN Consortium, Heckerman D, Rogaeva E, Zinman L, Rothstein JD, Sendtner M, Drepper C, Eichler EE, Alkan C, Abdullaev Z, Pack SD, Dutra A, Pak E, Hardy J, Singleton A, Williams NM, Heutink P, Pickering-Brown S, Morris HR, Tienari PJ, Traynor BJ. A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD. Neuron. 2011 Oct 20;72(2):257-68. Epub 2011 Sep 21.

Shefner J, Watson M, Simionescu L, Caress J, Burns T, Maragakis N, Benatar M, David W, Sharma K, Rutkove S. Modified incremental motor unit estimation in a longitudinal natural history study of subjects with ALS. Neurology. 2011 Jul 19;77(3):235-41.

Johnson JO, Mandrioli J, Benatar M, Abramzon Y, Van Deerlin VM, Trojanowski JQ, Gibbs JR, Brunetti M, Gronka S, Wuu J, Ding J, McCluskey L, Martinez-Lage M, Falcone D, Hernandez DG, Arepalli S, Chong S, Schymick JC, Rothstein J, Landi1 F, Wang M, Calvo A, Mora G, Sabatelli M, Monsurrò MR, Battistini S, Salvi F, Spataro R, Sola P, Borghero G, ITALSGEN, Galassi G, Scholz SW, Taylor JP, Restagno G, Chiò A, Traynor BJ. Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron. 2010 Dec 9;68(5):857-64.

Fanos J, Gronka S, Wuu J, Stanislaw C, Andersen P, Benatar M. Impact of pre-symptomatic testing for familial amyotrophic lateral sclerosis. Genet Med. 2011 Apr;13(4):342-8.

Benatar M, Polak M, Kaplan S, Glass J. Preventing familial amyotrophic lateral sclerosis: Is a clinical trial feasible? J Neurol Sci. 2006 Dec 21;251(1-2):3-9. Epub 2006 Sep 26.

Carew JD, Nair, G, Andersen PM, Wuu J, Gronka S, Hu X, Benatar M. Pre-symptomatic spinal cord neurometbolic findings in SOD1+ people at risk for famiilal ALS. Neurology. 2011 Oct 4; 77:1370-1375
Press Release

Presentations and Lectures

Nair G, Wuu J, Gronka S, Walker M, Carew J, Benatar M. MRI evidence of disease in pre-symptomatic SOD1+ individuals at risk for developing familial ALS. Accepted for platform presentation at the 22nd International Symposium on ALS/MND, Sydney, Australia, Nov 30 - Dec 2, 2011

Nair G, Gronka S, Lu D, Wuu J, Hu XP, Benatar M. Towards an imaging-metric for presymptomatic manifestations of ALS. Poster presentation at the International Society for Magnetic Resonance in Medicine 19th Annual Meeting, Montreal, Canada, May 7-13, 2011

Carew J, Nair G, Usher S, Hu X, Benatar M. Magnetic Resonance Spectroscopy of the Cervical Spine in ALS and Pre-symptomatic SOD1 Positive People. International Society for Magnetic Resonance in Medicine 19th Annual Meeting, Montreal, Canada, May 7-13, 2011

Gronka S, Walker M, Wuu J, Stanislaw C, Fanos J, Atassi N, Jaffa M, Andersen P, Cudkowicz M, Benatar M. Telemedicine to facilitate ALS research. Platform presentation at the 21st International Symposium on ALS/MND, Orlando, FL, Dec 11-13, 2010

Lu D, Rutkove S, Gronka S, Spieker A, Usher S, Wuu J, Andersen P, Benatar M. Electrical impedance myography (EIM) findings in pre-symptomatic SOD1+ subjects. Platform presentation at the 9th Annual Northeast ALS Consortium Meeting, Washington, DC, Oct 27-29, 2010

Tackling the Challenges of ALS: A Familial Perspective.
    21st International ALS/MND Meeting, Orlando, Florida, December 2010
    Neurology Grand Rounds, University of Miami. Miami, March, 2010
    Annual William L Halseth ALS Lecture, University of Colorado Denver. Aurora, February, 2010
    Neurology Grand Rounds, University of South Florida. Tampa, December, 2009
    20th International ALS/MND Meeting. Berlin, December 2009
    Neurology Grand Rounds, University of Virginia. Charlottesville, June 2009
    Human Genetics Grand Rounds, Emory University. Atlanta, February 2009

Electrical Impedance Myography as a Pre-Symptomatic Biomarker of ALS. Poster presentation by Sharon Usher at the 20th International Symposium on ALS/MND Meeting, Berlin, December 2009

Gronka S, Stanislaw C, Wuu J, Benatar M. Pre-symptomatic Testing for Familial ALS: The Pre-fALS Experience. Platform presentation by Sue Gronka at the Allied Health Professional Meeting affiliated with the 20th International Symposium on ALS/MND Meeting, Berlin, December 2009

Gronka S, Wuu J, Stanislaw C, Usher S, Benatar M. Early results from the Pre-familial ALS (Pre-fALS) Study. Poster presentations by Sue Gronka at the 8th Annual Northeast ALS Consortium Meeting, St. Pete’s Beach, Florida, October 2009

Benatar M, Polak M, Feng R. Predicting the Risk of Disease in Familial Amyotrophic Lateral Sclerosis. ANA Annual Meeting, Salt Lake City, September 2008

Predictive, Preventive and Therapeutic Studies in Familial ALS. ALS Association Annual Leadership Forum, California. Orange County, January 2008

Strategies for pre-symptomatic biomarker identification in familial ALS. Cold Spring Harbor Symposium on Drug Discovery, Biomarkers and Clinical Trials for ALS. Cold Spring Harbor, September 2007

The Challenge of Preventing ALS. Neurology Grand Rounds, Emory University, Atlanta, May 2007

The Feasibility of a Preventive Study in Familial ALS. 4th Annual Northeast Amyotrophic Lateral Sclerosis Consortium Meeting. Boston. September 2005