Scientists have discovered new genetic causes for a neurodegenerative group of diseases known as hereditary spastic paraplegia (HSP), characterized by stiffness and lack of mobility in the legs. According to the study published in Science, the research team has doubled the number of known causes for HSP.
“After uncovering so many novel genetic bases of HSP, we were in the unique position to investigate how these causes link together,” Dr. Joseph Gleeson, an author of the study and a professor in the University of California, San Diego, departments of Neurosciences and Pediatrics, said in a press release. “We were able to generate an ‘HSP-ome,’ a map that included all of the new and previously described causes.”
Hereditary spastic paraplegia (HSP), which is also known as familial spastic paraparesis (FSP), is a group of disorders that involve extreme weakness and stiffness — or spasticity — of the legs. The disease is progressive, meaning people who’ve inherited HSP will gradually need a cane, walker, or wheelchair, according to the National Institute of Neurological Disorders and Stroke (NINDS). HSP is also often linked to blindness, cognitive impairment, and epilepsy.
The study took several years to complete, and the UC San Diego researchers studied over 50 families that had autosomal recessive HSP, and used a technique known as exome sequencing, which maps out key portions of the genome. The researchers were able to find a particular genetic mutation in about 75 percent of the cases. Half of these genetic mutations were actually in genes that had never been linked to HSP before.
Gaia Novarino, another author of the study, said in the press release that the study “is important for the neurodegenerative research community. But more broadly, it offers an illustrative example of how, by utilizing genomics in specific patient populations, and then building an ‘interactome,’ we greatly expand knowledge around unknown causes of disease.”
The researchers believe that identifying biological processes behind the neurological disorder will help target new options for treatments. Currently, treatment for HSP simply involves muscle relaxants to help spasticity, as well as regular physical therapy. “Knowing the biological processes underlying neurodegenerative disorders is seminal to driving future scientific studies that aim to uncover the exact mechanisms implicated in common neurodegenerative diseases, and to indicate the path toward development of effective treatments,” Gleeson said in the press release.