Spastic Paraplegia - Centers of Excellence Research Network

The hereditary spastic paraplegias (HSPs) include over 80 rare neurogenetic disorders, collectively representing the most prevalent cause of inherited spasticity and related disabilities globally. In all forms of HSP, there is a progressive deterioration of the long axonal tracts, resulting in substantial motor dysfunction and various other symptoms. Primary lateral sclerosis (PLS) is a related, degenerative neurological disorder characterized by the progressive deterioration of upper motor neurons. Both conditions result in muscle weakness and spasticity, with significant morbidity and impact on quality of life.

The Spastic Paraplegia - Centers of Excellence Research Network (SP-CERN) is a collaborative research consortium dedicated to advancing the understanding, diagnosis, and treatment of hereditary spastic paraplegia (HSP) and primary lateral sclerosis (PLS). SP-CERN provides a registry and natural history study across the whole age span, a biobank, and a genome archive. This will set the stage for a multitude of opportunities for improved diagnosis and trial readiness. A second objective is to harmonize this effort with similar consortia, especially in Europe, in addition to Asia, South America, and Africa, to help accelerate basic and clinical research on HSP and PLS on a global level. In summary, SP-CERN will support critical research infrastructure for collaborative high-quality research on HSP and PLS in North America and beyond.

General aims include:

A. Establish a shared clinical database, a repository of biospecimen samples, and a central database for the storage of all genetic data in SP-CERN.

B. Synchronize and harmonize collaborations between institutions, clinical sites, and international collaborators through the development of a central research protocol in order to standardize outcome measures and maximize the quality of research and data to ensure clinical trial readiness by regulatory standards.

C. Build comprehensive programs for advancements in diagnosis, provide more opportunities for innovative treatments, and increase access to high-quality healthcare for HSP and PLS patients.

Specific aims for this first pilot study are:

1a. Enrollment of 100 individuals with genetically-confirmed hereditary spastic paraplegia type 4 (SPG4) or hereditary spastic paraplegia type 5A (SPG5A) in the shared clinical database.

1b. Biobanking of blood samples from 100 individuals with SPG4 or SPG5A in a shared biobank.

Primary outcomes

• Establish a shared clinical database, biobank of biospecimen samples, and a central repository for the storage of all genetic data in SP-CERN. [2 years]
• Synchronize collaborations between institutions and clinical sites through a central research protocol to standardize outcome measures and maximize the quality of research and data to ensure clinical trial readiness by regulatory standards. [2 years]
• Test key elements in pilot projects [2 years]
• Build comprehensive programs for advancements in diagnosis, provide more opportunities for innovative treatments, and increase access to high-quality healthcare for HSP and PLS patients. [2 years]

Secondary outcomes

• Enrollment of 100 individuals with hereditary spastic paraplegia type 4 (SPG4) or hereditary spastic paraplegia type 5A (SPG5A) in the shared clinical database. [2 years]
• Biobanking of blood samples from 100 individuals with SPG4 or SPG5A in a shared biobank. [2 years]

Sex: All

Inclusion Criteria:

* Male or female patients of all ages with a clinical and molecular diagnosis of hereditary spastic paraplegia type 4 (SPG4, SPAST) or hereditary spastic paraplegia type 5A (SPG5A, CYP7B1).

Exclusion Criteria:

* Not having such a diagnosis and/or not being related to such individual.