Spastic Paraplegia

Spastic paraplegia comprise a group of hereditary degenerative disorders that affect the upper motor neuron with relentlessness progressive gait disturbance due to spasticity and weakness as the clinical hallmark of the disease.

HSP-Network (GeNeMove)

The research project on hereditary spastic paraplegia (HSP) in the German Network of hereditary Movement disorders (GeNeMove: www.genemove.de) is coordinated in Tübingen. Major aims are the development of standards for the diagnostic evaluation of HSP, the differential diagnostic work-up, electrophysiological characterisation and magnetic resonance imaging. We developed and evaluated the first score to assess the severity of the disease. In a longitudinal study we presently investigate the natural course of the disease and analyse whether electrophysiological parameters or quantitative assessment of spinal cord atrophy are appropriate progression markers for therapeutical trials in the future.

Genetics of hereditary spastic paraplegia (HSP)

Although HSP is a rare disease with an prevalence of 0.5–1:100.000 it is highly heterogeneous with at least 32 genetically defined subtypes (s. Table "Molecular genetics of HSP"). For most families the responsible genetic defect is not yet identified. In families with autosomal dominant disease we perform haplotype analyses for all 11 so far characterized chromosomal loci. Appropriate pedigrees are analysed in a genome search using SNP chip technology. Recently we identified the first German SPG10 family with a novel mutation in KIF5a, an essential motor for anterograde axonal transport.
HSP with thin corpus callosum and autosomal recessive inheritance are hallmarks of SPG11. In cooperation with the Institute of Medical Genetics in Tübingen (Prof. Rieß) and the Department of Neurology in Regensburg (Prof. Winkler) we search for the gene responsible for SPG11 using a candidate gene approach.