OMB No. 0925-0001 and 0925-0002 (Rev. 09/17 Approved Through 03/31/2020)

NAME: Statland, Jeffrey M

eRA COMMONS USER NAME (credential, e.g., agency login): jstatland

POSITION TITLE: Associate Professor

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)

My research background has centered primarily on describing the natural history of and response to therapy for neuromuscular diseases. I completed a neuromuscular fellowship in Experimental Therapeutics of Neurological Diseases at the University of Rochester Medical Center, and I currently serve as principal investigator or co-investigator for research studies in Facioscapulohumeral muscular dystrophy (FSHD), Duchenne Muscular Dystrophy, Spinal Muscular Atrophy, and Myotonic Dystrophy. My specific research interest over the last 8 years has been preparing for clinical trials in FSHD.  I have systematically analyzed performance of strength and functional outcomes in prior FSHD clinical trials and compared to performance in a natural history study.  I have worked with my collaborators to develop new disease-relevant outcome measures to assess patient-reported disease burden, functional impairment, and physiological changes in muscle.  I regularly present at international meetings on research and clinical trial planning in FSHD (e.g. the American Academy of Neurology, the International Congress of Neuromuscular Disorders, and the FSHD Society International Consortium Meeting). I have obtained pilot data on the use of a number of novel outcomes for FSHD, including electrical impedance myography, a disease specific functional rating scale, and a wireless motion analysis system in FSHD. Currently we have assembled an FSHD Clinical Trial Research Network, 8 sites with expertise in performing neuromuscular clinical trials, and a team of evaluators and coordinators with decades of experience in conducting clinical trials.  We have received grant funding from NINDS to run what will be the largest natural history study of FSHD performed in the United States. For this project we will build on our prior work screening for serum biomarkers in FSHD using a multi-analyte panel.  For this project we will leverage our existing FSHD studies to obtain samples and clinical information.  This MDA secretome-influenced biomarker discovery and validation project will set the stage for an application for a larger FSHD biomarker project.  I will be collaborating with Rabi Tawil, MD, and Stephen Tapscott, MD, PhD who have decades of experience in FSHD research.

1. Statland JM, Donlin-Smith C, Tapscott S, van der Maarel S, Tawil R.  Multiplex screen of serum biomarkers in facioscapulohumeral muscular dystrophy.  J Neuromusc Dis 2014;1(2):181-190  doi: 10.3233/JND-140034; PMID: 25705588 PMCID: PMC4332410
2. Statland JM, Heatwole C, Eichinger K, Dilek N, Martens WB, Tawil R. Electrical impedance myography in facioscapulohumeral muscular dystrophy. Muscle Nerve. 2016, Feb 3. doi: 10.1002/mus.25065. [Epub ahead of print] PubMed PMID: 26840230. NIHM SID 774313.
3. Eichinger K, Heatwole C, Heininger S, Stinson N, Matichak Stock C, Grosmann C, Wagner KR, Tawil R, Statland JM; FSHD Clinical Trials Research Network. Validity of the Six Minute Walk Test in Facioscapulohumeral Muscular Dystrophy. Muscle Nerve. 2016 Jul 16. doi: 10.1002/mus.25251. [Epub ahead of print] PubMed PMID: 27421252.
4. Eichinger K, Heatwole C, Iyadurai S, King W, Baker L, Heininger S, Bartlett A, Dilek N, Martens WB, Mcdermott M, Kissel JT, Tawil R, Statland JM. Facioscapulohumeral muscular dystrophy functional composite outcome measure. Muscle Nerve. 2018 Jan 30. doi: 10.1002/mus.26088. [Epub ahead of print] PubMed PMID: 29381807; PubMed Central PMCID: PMC6066464.

Positions and Employment

Other Experience and Professional Memberships

Honors

1. Refining the Natural History of FSHD
   We have conducted a number of studies to refine our understanding of the natural history of FSHD, one of the most prevalent muscular dystrophies, and the relationship of genetics to clinical features and disease severity in FSHD.  We have analyzed data from the largest US Registry of FSHD patients which contains over 6 years of longitudinal data on genetically defined FSHD patients.  We have used a large prospective molecular pathology study in FSHD, along with collaborations with our colleagues in Seattle and the Netherlands, to better define the relationship of the residual D4Z4 fragment size or methylation status to expression of disease.  We have broadened our understanding on extra-muscular manifestations of FSHD.

1. Statland JM, Sacconi S, Farmakidis C, Donlin-Smith CM, Chung M, Tawil R. Coats syndrome in facioscapulohumeral dystrophy type 1: Frequency and D4Z4 contraction size. Neurology. 2013 Mar 26;80(13):1247-50. PubMed PMID: 23446679. PubMed Central PMCID: PMC3691782
1. Scully MA, Eichinger KJ, Donlin-Smith CM, Tawil R, Statland JM. Restrictive Lung Involvement in Facioscapulohumeral Muscular Dystrophy. Muscle Nerve. 2014. Epub 2014/03/19. doi: 10.1002/mus.24218. PubMed PMID: 24639337. PMCID: PMC4142113
2. Statland JM, Tawil R. Risk of functional impairment in Facioscapulohumeral muscular dystrophy. Muscle Nerve. 2014 Apr;49(4):520-7. PubMed PMID: 23873337.
3. Statland JM, Donlin-Smith C, Tapscott S, Lemmers R, van der Maarel S, and Tawil R.  Milder Phenotype in Facioscapulohumeral Dystrophy Patients with 7-10 Residual D4Z4 Repeats.  Neurology. 015 Dec 15;85(24):2147-50. PubMed PMID: 26561289. PMCID: PMC4691686

1. Clinical Trials in Neuromuscular Diseases
   The goal of outcome measure development is to conduct clinical trials to find new therapies for neuromuscular diseases.  I have not only had experience defining the natural history of neuromuscular disease, but have translated these findings into the setting of clinical trials.  I played a key role in the design and conduct of a clinical trial of mexiletine for non-dystrophic myotonias.  I helped design a study which was subsequently conducted in cooperation with our colleagues in the UK looking at a novel heat shock protein promotor in inclusion body myositis.  I have helped in the data analysis and publication of scientific publications in ALS.

1. Statland JM, Bundy BN, Wang Y, Rayan DR, Trivedi JR, Sansone VA, et al. Mexiletine for symptoms and signs of myotonia in nondystrophic myotonia: a randomized controlled trial. JAMA. 2012;308(13):1357-65. PMCID: PMC3564227
2. Macchi Z, Wang Y, Moore D, Katz J, Saperstein D, Walk D, Simpson E, Genge A, Bertorini T, Fernandes JA, Swenson A, Elman L, Dimachkie M, Herbelin L, Miller J, Lu J, Wilkins H, Swerdlow RH, Statland J, Barohn R; Western ALS (WALS) Rasagiline Study Group. A multi-center screening trial of rasagiline in patients with amyotrophic lateral sclerosis: Possible mitochondrial biomarker target engagement. Amyotroph Lateral Scler Frontotemporal Degener. 2015 Apr 2:1-8. [Epub ahead of print] PubMed PMID: 25832828. PMCID: PMC4610861
3. Ahmed M, Machado PM, Miller A, Spicer C, Herbelin L, He J, Noel J, Wang Y, McVey AL, Pasnoor M, Gallagher P, Statland J, Lu CH, Kalmar B, Brady S, Sethi H, Samandouras G, Parton M, Holton JL, Weston A, Collinson L, Taylor JP, Schiavo G, Hanna MG, Barohn RJ, Dimachkie MM, Greensmith L. Targeting protein homeostasis in sporadic inclusion body myositis. Sci Transl Med. 2016 Mar 23;8(331):331ra41. doi: 10.1126/scitranslmed.aad4583. PubMed PMID: 27009270. PMCID: PMC5043094
4. Statland, JM, Moore, D, Wang, Y, Walsh, M, Mozaffar, T, Elman, L, Nations, S, Mitsumoto, H, Fernandes, JA, Saperstein, D, Hayat, G, Herbelin, L, Karam, C, Katz, J, Wilkins HM, Agbas, A, Swerdlow, RH, Santella, RM, Dimachkie, MM, Barohn, RJ, and the Rasagiline Investigators of the Muscle Study Group and Western ALS Consortium. Rasagiline for Amyotrophic Lateral Sclerosis: a Randomized Controlled Trial. Muscle and Nerve. 2018. NIHM SID 988122.

1. Developed outcome measures for FSHD
   We systematically reviewed the performance of established outcome measures in FSHD, with the specific goal of preparing for forthcoming clinical trials. Currently, I am the PI on a 7 center FSHD Clinical trial Research Network, and a NINDS U01 study on clinical trial preparedness for FSHD.  My experience working on outcome measure development for other neuromuscular diseases, which includes multi-center studies, has helped prepare me for my role working to coordinate the key partners for our current ALS study.

1. Statland JM, Shah B, Henderson D, Van Der Maarel S, Tapscott SJ, Tawil R. Muscle pathology grade for facioscapulohumeral muscular dystrophy biopsies. Muscle Nerve. 2015 Oct;52(4):521-6. doi: 10.1002/mus.24621. Epub 2015 Jun 18. PubMed PMID: 25704033; PubMed Central PMCID: PMC4546927.
2. Huisinga J, Bruetsch A, Mccalley A, Currence M, Herbelin L, Jawdat O, Pasnoor M, Dimachkie M, Barohn R, Statland J. An instrumented timed up and go in facioscapulohumeral muscular dystrophy. Muscle Nerve. 2018 Mar;57(3):503-506. PubMed PMID: 28877559.
3. Mul K, Heatwole C, Eichinger K, Dilek N, Martens WB, Van Engelen BGM, Tawil R, Statland JM. Electrical impedance myography in facioscapulohumeral muscular dystrophy: A 1-year follow-up study. Muscle Nerve. 2018 Aug;58(2):213-218. doi:10.1002/mus.26127. Epub 2018 Apr 17. PubMed PMID: 29543984; PubMed Central PMCID: PMC6105423.

1. Clinical Trial Preparedness in Non-Dystrophic Myotonias
   I have experience developing outcome measures for other diseases.  Clinical evaluation of patients with non-dystrophic myotonias remains a challenge: because these disorders are both extremely rare and highly variable, it is difficult to devise effective research able to provide investigators with clinically meaningful information. I have comprehensive experience in developing outcome measures for this purpose, and have demonstrated success in implementing innovative research designs that target theurapeutic interventions for non-dystrophic myotonias.

1. Statland JM, Wang Y, Richesson R, Bundy B, Herbelin L, Gomes J, Trivedi J, Venance S, Amato A, Hanna M, Griggs R, Barohn RJ. An interactive voice response diary for patients with non-dystrophic myotonia. Muscle Nerve. 2011 Jul;44(1):30-5. PubMed PMID: 21674518; PubMed Central PMCID: PMC3233757.
2. Statland JM, Bundy BN, Wang Y, Trivedi JR, Raja Rayan D, Herbelin L, Donlan M, McLin R, Eichinger KJ, Findlater K, Dewar L, Pandya S, Martens WB, Venance SL, Matthews E, Amato AA, Hanna MG, Griggs RC, Barohn RJ. A quantitative measure of handgrip myotonia in non-dystrophic myotonia. Muscle Nerve. 2012 Oct;46(4):482-9. PubMed PMID: 22987687; PubMed Central PMCID: PMC3564214.
3. Trivedi JR, Bundy B, Statland J, Salajegheh M, Rayan DR, Venance SL, et al. Non-dystrophic myotonia: prospective study of objective and patient reported outcomes. Brain. 2013;136(Pt 7):2189-200. PMID: 23771340, PMCID: PMC3692030
1. Stunnenberg BC, Woertman W, Raaphorst J, Statland JM, Griggs RC, Timmermans J, Saris CG, Schouwenberg BJ, Groenewoud HM, Stegeman DF, van Engelen BG, Drost G, van der Wilt GJ. Combined N-of-1 trials to investigate mexiletine in non-dystrophic myotonia using a Bayesian approach; study rationale and protocol. BMC Neurol. 2015 Mar 25;15(1):43. PubMed PMID: 25880166; PubMed Central PMCID: PMC4407841.

1. Advancements in Cellular Neurophysiology
   My experience in the Howard Hughes Medical Institute-NIH program has provided me with valuable preclinical experience that has been integral for my development as a clinical researcher. During my training as an HHMI Research Scholar, I investigated how neuromodulatory systems affect information processing in hippocampal neurons using rodent models.My work identifying and initializing a hyperpolarizing M-current provided a direct contribution to 3 publications.
   1. Lawrence JJ, Statland JM, Grinspan ZM, McBain CJ. Cell type-specific dependence of muscarinic signalling in mouse hippocampal stratum oriens interneurones. J Physiol. 2006 Feb 1;570(Pt 3):595-610. PubMed PMID: 16322052; PubMed Central PMCID: PMC1479881.
   2. Lawrence JJ, Grinspan ZM, Statland JM, McBain CJ. Muscarinic receptor activation tunes mouse stratum oriens interneurones to amplify spike reliability. J Physiol. 2006 Mar 15;571(Pt 3):555-62. PubMed PMID: 16439425; PubMed Central PMCID: PMC1805794.
   3. Lawrence JJ, Saraga F, Churchill JF, Statland JM, Travis KE, Skinner FK, McBain CJ. Somatodendritic Kv7/KCNQ/M channels control interspike interval in hippocampal interneurons. J Neurosci. 2006 Nov 22;26(47):12325-38. PubMed PMID: 17122058.
      Complete List of Published Work in My Bibliography: https://www.ncbi.nlm.nih.gov/sites/myncbi/jeffrey.statland.2/bibliography/48331678/public/?sort=date&direction=ascending

Ongoing Research Support

NINDS U01 (1U01NS101944)                                                                                            06/2017-present

Clinical Trial Readiness to Solve Barriers to Drug Development in FSHD.  The primary cause of facioscapulohumeral muscular dystrophy (FSHD) was recently discovered identifying targets for therapy. As multiple drug companies pursue treatments for FSHD, there is an urgent need to define the clinical trial strategies which will hasten drug development, including creating disease-relevant outcome measures and optimizing inclusion criteria. This proposal will develop two new outcome measures and optimize eligibility criteria by testing 150 patients in 7 sites over a period of 18 months.

Role PI (Jeffrey Statland, MD / Rabi Tawil, MD).

Muscular Dystrophy Association (573783)                                                                           6/2018-present

The goal of this project is to assemble An FSHD Clinical Trial Research Network.  We have 7 sites with neuromuscular clinical trial experience, and have leveraged existing infrastructure from the Muscle Study Group, and regulatory initiatives developed as part of the CTSA infrastructure

Role: PI (Jeffrey Statland, MD)

FDA OPD Research Grant (1R01FD006071)                                                                      9/2017-present

Establishing biomarkers and clinical trial endpoints in Myotonic Dystrophy Type 1. Myotonic dystrophy causes progressive disability and premature death. The burden on affected individuals, care givers, and families is high. This proposal seeks to develop the essential clinical research tools that are needed to evaluate new drug treatments for myotonic dystrophy. The long-term goal is to promote the development of treatments that prevent the disease, slow the progression, reduce the disability, or reverse the symptoms.

Role: site PI

FSH Society Research Grant (82015)                                                                                  2/2015-present

To determine the initial responsiveness to FSHD disease progression of a system of synchronized wireless motion sensors, and automated motion analysis software

Role: PI

Completed Research Support

CTSA Multi-Institutional Pilot Award                                                                                   10/2015-12/2017

To develop A Rausch-Built Clinical Severity Scale for FSHD for use in a large study to determine genetic modifiers of disease progression in FSHD

Role: Co-PI (Jeffrey Statland, MD / Nicholas Johnson, MD)

KL2TR000119                                                                                                                     07/2014-12/2016

The Relationship of Electrical Impedance Myography to Muscle Structure and Function in Facioscapulohumeral Muscular Dystrophy (REM-FSH). The goal of this study is to determine the relationship of EIM measurements to changes on MRI and muscle pathology.

Role: PI                                              

CTSA Frontier’s Pilot Award                                                                                             02/2015-2/2016

A portable wireless motion capture system for patients with Facioscapulohumeral Muscular Dystrophy

The goal of this study is to determine the reliability and relationship to disease severity of a wireless gait analysis system in FSHD.

Role: PI