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Researcher | Research Overview

The Ebrahimi-Fakhari lab is committed to understanding the molecular underpinnings of genetic childhood-onset movement disorders. By doing so, we strive to pave the way for the development of novel therapies for rare diseases, encompassing both small molecules and gene-based approaches.

Our approach to research is truly translational, as we merge two fundamental programs. Firstly, our clinical research program is dedicated to delineating the genetic foundations of childhood-onset movement disorders and neurodegenerative diseases. Through comprehensive clinical studies, we not only identify the genetic roots of these conditions but also prepare the groundwork for clinical trials. Our natural history studies and biomarker discovery efforts ensure clinical trial readiness, while simultaneously establishing a robust infrastructure for first-in-human and later phase pivotal clinical investigations. Secondly, our basic science research program investigates the cellular biology and mechanisms underlying neurodegeneration in childhood-onset movement disorders. We employ a multidisciplinary approach, integrating genetics, biochemistry, cell biology, pharmacology, high-throughput microscopy, and disease modeling. Through the utilization of cutting-edge techniques and model organisms such as human cell lines, induced pluripotent stem cell-derived neurons, transgenic zebrafish and mice, we aim to shed light on the complex processes underlying neurogenetic diseases. At our lab, we are passionate about bridging the gap between scientific discoveries and tangible clinical applications. Our ultimate goal is to improve the lives of children affected by neurogenetic disorders through the development of innovative and effective therapies.

The translational research in the Ebrahimi-Fakhari work is closely aligned with the clinical care of children and young adults in the Boston Children’s Hospital Movement Disorders Program and the Movement Disorders & Neurogenetics Fellowship Program.

Some of the current funded research projects in the lab include:

  • A Translational Research Platform for Childhood-Onset Hereditary Spastic Paraplegia
  • An International Registry and Natural History Study for Early-Onset Hereditary Spastic Paraplegia [ClinicalTrials.gov Identifier: NCT04712812]
  • The Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq) [ClinicalTrials.gov Identifier: NCT05354622]
  • Development of a Translational Research Platform to Understand and Treat Defective Protein Trafficking in Childhood-Onset Hereditary Spastic Paraplegia
  • Functional Genomic Screen To Identify Novel Therapeutic Targets For Childhood-Onset Hereditary Spastic Paraplegia
  • An Unbiased Phenotypic Screen for Novel Therapeutic Targets in AP-4-associated HSP
  • Using Primary Fibroblasts and iPSC-Derived Neurons from Patients with AP-4-associated Hereditary Spastic Paraplegia to Support an Unbiased Autophagy-based Phenotypic Screening for Novel Therapeutic Targets
  • Characterization of ap4b1-/- zebrafish as a novel in vivo model of SPG47 and its application in small molecule screens
  • Development and Characterization of a Novel In Vivo Model of BPAN Using CRISPR/Cas9-based Knockout of wdr45 in Zebrafish
  • Investigating the effect of chronic treatment with small molecule modulators of protein trafficking on biochemical, morphological and behavioral phenotypes in Ap4b1 knockout mice

Researcher | Research Background

Darius Ebrahimi-Fakhari, M.D., Ph.D., is a Child Neurologist and Neuroscientist with special expertise in childhood-onset neurogenetic, neurodegenerative, and movement disorders. He serves the Director of the Movement Disorders Program and the Movement Disorders and Neurogenetic Fellowship Program. As a physician-scientist, the objective of his research is to understand the genetic and molecular mechanisms of childhood-onset movement disorders, and to use this knowledge to develop novel therapeutic approaches to treat and cure a variety of neurological diseases. Dr. Ebrahimi-Fakhari received his M.D. and Ph.D. degrees from the Ruprecht Karl University of Heidelberg, Germany.

After graduating, he trained in Pediatrics at Heidelberg University Hospital before returning to neuroscience research as a postdoctoral research fellow at the F.M. Kirby Neurobiology Center and the Department of Neurology at Boston Children’s Hospital, to study mechanisms of protein trafficking and degradation in neurons. After additional residency training in Pediatrics and Child Neurology at Boston Children’s Hospital and the Harvard Neurology Program, he completed a clinical fellowship in Movement Disorders at Boston Children’s Hospital and Massachusetts General Hospital.

Over the last years, Dr. Ebrahimi-Fakhari’s team has built a translational research program for childhood-onset movement disorders and neurodegenerative diseases. He has been awarded the Outstanding Junior Member Award from the Child Neurology Society three times, in 2016, 2019 and 2021, the Outstanding Investigator Award from the German Society for Pediatric Neurology in 2017, and the Young Physician Scientist Award from the American Society of Clinical Investigation in 2023.

Work in the Ebrahimi-Fakhari lab has been supported the NIH/NINDS, the Spastic Paraplegia Foundation, Thrasher Research Foundation, CureAP4 Foundation, CureSPG50 Foundation, Tom-Wahlig Foundation, The Manton Center for Orphan Disease Research, the BCH Office of Faculty Development, the BCH Translational Research Program the and Astellas Pharmaceuticals

Researcher | Publications