Scientists discover many new genetic forms of neurodegeneration

In a study published in the journal Science on January 31, an international team of researchers, led by scientists at the University of California San Diego School of Medicine, including Gaia Novarino, now Assistant Professor at IST Austria, reported to have doubled the number of known causes for the neurodegenerative disorder known as hereditary spastic paraplegia (HSP). HSP is characterized by progressive stiffness and contraction of the lower limbs and is associated with epilepsy, cognitive impairment, blindness and other neurological features in some cases.

Over the course of several years, the team of researchers at UCSD recruited a cohort of over 50 families displaying autosomal recessive HSP, the largest such cohort assembled to date. The scientists analyzed about 100 patients from this cohort using a technique called whole exome sequencing (WES), a method to sequence the important parts of the genome.  They identified a genetic mutation in almost 75% of the cases, half of which were in genes that had never been linked with human disease.

“After uncovering so many novel genetic basis of HSP we were in the unique position to investigate how these causes link together and we were able to generate what we called an HSP-‘ome’, a map including all the new and previously described causes”, explains senior author Joseph G. Gleeson, MD Professor at UC San Diego and Investigator with the Howard Hughes Medical Institute.

The generation of the HSP-‘ome’ helped the team spot and later validate even more genetic mutations in their patients and to indicate key biological pathways underlying HSP. In addition, the researchers were interested to understand how HSP relates to other groups of disorders and found that the HSP-‘ome’ links HSP to other more common neurodegenerative disorders as Alzheimer’s and amyotrophic lateral sclerosis.

“Knowing the biological processes underlying neurodegenerative disorders is seminal to drive future scientific studies that aim to uncover the exact mechanisms implicated in common neurodegenerative diseases and to indicate the path toward the development of effective treatments” said Joseph G. Gleeson.

“I believe this study is important for the neurodegenerative research community” says lead author Gaia Novarino “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.”

Gaia Novarino joined IST Austria as Assistant Professor at the beginning of 2014. Novarino studied Molecular Biology and received her PhD in Cell Biology in 2006 at La Sapienza University in Rome, Italy. Novarino spent four years as postdoctoral fellow at the Max Delbrück Center for Molecular Medicine in Berlin before moving to the laboratory of Joseph Gleeson at University of California San Diego in 2010, where she was focused on identifying novel genetic basis of cognitive disorders and carried out the research now published in Science.