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.
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.
| Nicolas, Aude (see original citation for additional authors) (2018) Genome-wide Analyses Identify KIF5A as a Novel ALS Gene. Neuron 97:1268-1283.e6 |
| Wilke, Carlo; Rattay, Tim W; Hengel, Holger et al. (2018) Serum neurofilament light chain is increased in hereditary spastic paraplegias. Ann Clin Transl Neurol 5:876-882 |
| Lassuthova, Petra; Rebelo, Adriana P; Ravenscroft, Gianina et al. (2018) Mutations in ATP1A1 Cause Dominant Charcot-Marie-Tooth Type 2. Am J Hum Genet 102:505-514 |
| Chen, Jacqueline; Kostenko, Volodymyr; Pioro, Erik P et al. (2018) MR Imaging-based Estimation of Upper Motor Neuron Density in Patients with Amyotrophic Lateral Sclerosis: A Feasibility Study. Radiology 287:955-964 |
| Pottier, Cyril; Rampersaud, Evadnie; Baker, Matt et al. (2018) Identification of compound heterozygous variants in OPTN in an ALS-FTD patient from the CReATe consortium: a case report. Amyotroph Lateral Scler Frontotemporal Degener 19:469-471 |
| Prudencio, Mercedes; Gonzales, Patrick K; Cook, Casey N et al. (2017) Repetitive element transcripts are elevated in the brain of C9orf72 ALS/FTLD patients. Hum Mol Genet 26:3421-3431 |
| Jacquier, Arnaud; Delorme, Cécile; 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 |
| Finch, NiCole A; Wang, Xue; Baker, Matthew C et al. (2017) Abnormal expression of homeobox genes and transthyretin in C9ORF72 expansion carriers. Neurol Genet 3:e161 |
| 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: |
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