Boston Children's Hospital secures $8.1M for spastic paraplegia research

Boston Children's Hospital has received $8.1M in NIH funding to support and expand the Spastic Paraplegia Centers of Excellence Research Network (SP-CERN). Darius Ebrahimi-Fakhari, M.D., Ph.D., Director of the Movement Disorders Program at Boston Children's, and his team will lead this multi-center effort.

Hereditary spastic paraplegias (HSPs) are a diverse group of more than 80 neurodegenerative disorders characterized by progressive spasticity and weakness of the lower extremities, leading to significant disability and reduced quality of life. Despite the growing understanding of the genetic causes of HSPs, therapeutic options remain limited, leaving a critical unmet medical need.

The grant, funded by National Institute of Neurological Disorders and Stroke (NINDS), National Center for Advancing Translational Sciences (NCATS), National Institute of Child Health and Human Development (NICHD), and National Human Genome Research Institute (NHGRI), will focus on advancing research and promoting clinical trial readiness for these disorders. It represents a huge milestone for the HSP community and for Ebrahimi-Fakhari, who's journey with the disease began with a single patient encounter during his residency at Boston Children's nearly a decade ago.

In 2016, he met two little girls with spasticity and decreased muscle tone in their legs, which affected their walking. Both girls had been diagnosed with the same rare subtype of HSP, caused by mutations in the gene for HSP type 47, or SPG47. The only other cases of SPG47 then known were from four families in the Middle East. Aside from interventions like occupational, physical, and speech therapy, there were no treatments. As a PhD student, Ebrahimi-Fakhari had studied autophagy, a cellular recycling process that's known to be disrupted by mutations in the SPG47 gene – now he wanted to investigate the root cause of SPG47 and perhaps find a treatment.

Fast forward to today where the landscape has drastically changed, thanks in large part to efforts at Boston Children's. Ebrahimi-Fakhari's lab has found a potential drug that may work for several subtypes of HSP, including SPG47, and two gene therapies have advanced to clinical testing, including a recently approved first in human phase 1/2 clinical trial at Boston Children's Hospital (ClinicalTrials.gov ID NCT06948019) .

In 2022, Ebrahimi-Fakhari's team at Boston Children's also launched the HSP Genomic Sequencing Initiative and the Spastic Paraplegia Centers of Excellent Research Network (SP-CERN). The SP-CERN is a consortium of 11 centers across the United States that collaborates to create clinical trial readiness and facilitate clinical trials for children and adults with HSP. With the newest grant the SP-CERN is becoming part of the NIH Rare Diseases Clinical Research Network (RDCRN) supporting the further expansion of the network and marking an exciting new chapter for the work at Boston Children's.

"This milestone did not happen overnight, said Ebrahimi-Fakhari. "It represents months, and in many ways, years, of hard work, collaboration, and dedication from so many people who share the same vision: to improve the lives of individuals and families living with HSP."