The Clinical Research in ALS and related disorders for Therapy Development (CREATE) RDCRC will focus on ALS and a group of related degenerative disorders that includes PLS, HSP, PMA, and FTD. This group of disorders is unified by their degenerative nature;their overlapping phenotypes resulting from degeneration of upper motor neuron, lower motor neuron and frontotemporal neuronal systems;their overlapping genetic susceptibility;their shared underlying biology;and their uniform lack of effective therapies. These disorders also share common challenges with respect to biomarker and therapeutic development - challenges that might be overcome through a shared experimental approach. The over-arching goals of the CREATE RDCRC are to better understand the relationship between genotype and phenotype for this group of disorders, and to develop disease biomarkers with a view to facilitating drug discovery and therapeutic development for patients afflicted with one of these neurodegenerative disorders. The CREATE RDCRC brings together a multi-disciplinary group of investigators and a diverse array of patient advocacy groups representing the patient populations that are the focus of our research efforts. These include the ALS Association, the Muscular Dystrophy Association, the Spastic Paraplegia Foundation, the Association for Frontotemporal Degeneration, the ALS Recovery Fund and PatientsLikeMe. The diversity of expertise within the CREATE RDCRC spans clinical neurology (neuromuscular disease and cognitive/behavioral neurology), genetics, genetic epidemiology, molecular neuroscience, biomarker development, drug discovery, biostatistics, and clinical trials, as well as patient advocacy, education and outreach. The CREATE Consortium, therefore, is a truly translational enterprise that effectively bridges the gap between basic scientists and investigators engaged in applied clinical research. Our new collaboration with the Ontario Brain Institute Neurodegenerative Disease Research Initiative, and the European STRENGTH Consortium significantly enhance the potential impact of this RDCRC.

Public Health Relevance

ALS, PLS, HSP, PMA and FTD are all characterized by degeneration of motor and frontotemporal neuronal systems. Effective therapies for these disorders are sorely needed. Disease heterogeneity and a paucity of biomarkers have hampered therapeutic development efforts. The goals of this RDCRC are to overcome these obstacles and thereby to advance therapeutic development for this group of rare diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
1U54NS092091-01
Application #
8762599
Study Section
Special Emphasis Panel (ZTR1-CI-8 (01))
Program Officer
Gubitz, Amelie
Project Start
2014-09-30
Project End
2019-06-30
Budget Start
2014-09-30
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
$1,235,166
Indirect Cost
$288,415
Name
University of Miami School of Medicine
Department
Neurology
Type
Schools of Medicine
DUNS #
052780918
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
DeJesus-Hernandez, Mariely; Finch, NiCole A; Wang, Xue et al. (2017) In-depth clinico-pathological examination of RNA foci in a large cohort of C9ORF72 expansion carriers. Acta Neuropathol 134:255-269
Gendron, Tania F; Chew, Jeannie; Stankowski, Jeannette N et al. (2017) Poly(GP) proteins are a useful pharmacodynamic marker for C9ORF72-associated amyotrophic lateral sclerosis. Sci Transl Med 9:
Gendron, Tania F; C9ORF72 Neurofilament Study Group; Daughrity, Lillian M et al. (2017) Phosphorylated neurofilament heavy chain: A biomarker of survival for C9ORF72-associated amyotrophic lateral sclerosis. Ann Neurol 82:139-146
Jacquier, Arnaud; Delorme, C├ęcile; Belotti, Edwige et al. (2017) Cryptic amyloidogenic elements in mutant NEFH causing Charcot-Marie-Tooth 2 trigger aggresome formation and neuronal death. Acta Neuropathol Commun 5:55
Esanov, Rustam; Cabrera, Gabriela Toro; Andrade, Nadja S et al. (2017) A C9ORF72 BAC mouse model recapitulates key epigenetic perturbations of ALS/FTD. Mol Neurodegener 12:46
Mackenzie, Ian R; Nicholson, Alexandra M; Sarkar, Mohona et al. (2017) TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics. Neuron 95:808-816.e9
Benatar, Michael; Boylan, Kevin; Jeromin, Andreas et al. (2016) ALS biomarkers for therapy development: State of the field and future directions. Muscle Nerve 53:169-82
Esanov, Rustam; Belle, Kinsley C; van Blitterswijk, Marka et al. (2016) C9orf72 promoter hypermethylation is reduced while hydroxymethylation is acquired during reprogramming of ALS patient cells. Exp Neurol 277:171-177
Rebelo, Adriana P; Abrams, Alexander J; Cottenie, Ellen et al. (2016) Cryptic Amyloidogenic Elements in the 3' UTRs of Neurofilament Genes Trigger Axonal Neuropathy. Am J Hum Genet 98:597-614
Rossor, Alexander M; Oates, Emily C; Salter, Hannah K et al. (2015) Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2. Brain 138:293-310

Showing the most recent 10 out of 15 publications