Phenotype, Genotype & Biomarkers in ALS and Related Disorders

Conditions: Multisystem Proteinopathy
Amyotrophic Lateral Sclerosis
Frontotemporal Dementia
Progressive Muscular Atrophy
Primary Lateral Sclerosis
Hereditary Spastic Paraplegia

Brief Summary: The goals of this study are: (1) to better understand the relationship between the phenotype and genotype of amyotrophic lateral sclerosis (ALS) and related diseases, including primary lateral sclerosis (PLS), hereditary spastic paraplegia (HSP), progressive muscular atrophy (PMA), and frontotemporal dementia (FTD); and (2) to develop biomarkers that might be useful in aiding therapy development for this group of disorders.

Detailed Description: This study will recruit patients with ALS, ALS-FTD, PLS, HSP, and PMA, with a focus on incident cases. Patients with both familial and sporadic forms of these diseases will be enrolled and followed longitudinally using a standardized set of evaluations. Biological samples (blood, urine, CSF) will be collected from all study participants, and will be used for biomarker discovery and validation. Family members of affected individuals may also be enrolled and asked to contribute DNA and biological samples to aid genetic and biomarker discovery.

Recruitment & Eligibility

Inclusion Criteria

Member of at least one of the following categories:
1. Individuals with a clinical diagnosis of ALS or a related disorder, including FTD, HSP, PLS, PMA and MSP (sporadic or familial).
2. Family member of an enrolled affected individual.
Able and willing to comply with relevant procedures.

Exclusion Criteria

Affected with end or late stage disease.
A condition or situation which, in the PI's opinion, could confound the study finding or may interfere significantly with the individual's participation and compliance with the study protocol. This includes (but is not limited to) neurological, psychological and/or medical conditions.

Primary Outcome Measures

Name	Time	Method
Genetic determinants of phenotype	24 months	By combining longitudinally collected deep phenotypic data with deep genetic data (e.g. whole exome or whole genome sequencing), this project aims to define genetic variants that are associated with identifiable phenotypic features in patients with ALS and related disorders.
Phenotypic correlates of genotype	24 months	Using longitudinally collected deep phenotypic data, this project aims to define the natural history (i.e. temporal rate of disease progression) of the motor and frontotemporal system (behavior, cognition and language) phenotypes of ALS and related disorders in patients with identifiable genetic mutations.

Secondary Outcome Measures

Name	Time	Method

Locations (15): Twin Cities ALS Research Consortium
🇺🇸
Minneapolis, Minnesota, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
University of Texas Southwestern (UTSW)
🇺🇸
Dallas, Texas, United States
University of Texas Health Science Center San Antonio (UTHSCSA)
🇺🇸
San Antonio, Texas, United States
University of California San Diego (UCSD)
🇺🇸
San Diego, California, United States
California Pacific Medical Center (CPMC)
🇺🇸
San Francisco, California, United States
University of Virginia (UVA)
🇺🇸
Charlottesville, Virginia, United States
University of Miami
🇺🇸
Miami, Florida, United States
University of Iowa
🇺🇸
Iowa City, Iowa, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Kansas University Medical Center (KUMC)
🇺🇸
Kansas City, Kansas, United States
Stanford University
🇺🇸
Palo Alto, California, United States
University of Cape Town
🇿🇦
Cape Town, South Africa
Wake Forest University
🇺🇸
Winston-Salem, North Carolina, United States
Eberhard Karls University of Tübingen
🇩🇪
Tübingen, Germany