Supports current direction towards clinical trials
Converging themes in the cellular mechanisms and causes of the most common forms of HSP, emerging from multiple studies over recent years have prompted leading researcher and globally respected authority on HSP, Dr Craig Blackstone of the National Institutes of Health in the USA, to conclude that organelle and cell membrane production, structure and function, as well as cargo trafficking in the axons of neurons, provide compelling targets for potential therapies.
This conclusion both draws on and supports the direction of the HSP research program in Australia, supported and facilitated by this Foundation, in pursuing clinical drug trials based on restoration of impaired cell functions in laboratory experiments with HSP-patient derived stem cells and neurons.
Abstract
Hereditary spastic paraplegias (HSPs) are neurologic disorders characterized by prominent lower-extremity spasticity, resulting from a length-dependent axonopathy of corticospinal upper motor neurons. They are among the most genetically-diverse neurologic disorders, with >80 distinct genetic loci and over 60 identified genes.
Studies investigating the molecular pathogenesis underlying HSPs have emphasized the importance of converging cellular pathogenic themes in the most common forms of HSP, providing compelling targets for therapy. Most notably, these include organelle shaping and biogenesis as well as membrane and cargo trafficking.
SOURCE: Curr Opin Neurobiol. 2018 Aug;51:139-146. doi: 10.1016/j.conb.2018.04.025. Epub 2018 May 10. PMID: 29753924
Converging cellular themes for the hereditary spastic paraplegias.
1 Cell Biology Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 35, Room 2A-201, 9000 Rockville Pike, Bethesda, MD 20892, USA.