Research Impact

The Spastic Paraplegia Foundation is dedicated to advancing research and ultimately finding the cures for two closely related groups of neurodegenerative disorders termed Hereditary Spastic Paraplegia (HSP) and Primary Lateral Sclerosis (PLS). These conditions share the common pathologic feature of degeneration principally of the upper motor neurons.

Scientists have unraveled many of the riddles regarding the complicated biochemistry of these diseases. Many HSP genes have now been discovered as well as a gene for PLS. Animal models for these disorders have been developed. They will enable investigators to further uncover the biochemical processes that cause nerve degeneration and identify and test therapy targets.

An increased focus on our diseases is timely and critical. There is indeed reason to hope for treatments and therapies in coming years that will restore significant function to people affected by SPF diseases. And, uncovering more of these riddles may also lead to important findings for related conditions such as ALS, spinal cord injury and Alzheimer’s Disease. Researchers say common threads link the many neurologic conditions that affect millions of people.

Research Grants Awarded by SP Foundation

  • 2014
    Holger Sondermann, Ph.D.

    Holger Sondermann, Ph.D., Associate Professor, Department of Molecular Medicine, Cornell Univ., Ithaca, NY.

    “Towards a Mechanistic Understanding and Targeted Therapies in HSP type SPG3A”

  • Evan A. L. Reid, Ph.D.

    Evan A. L. Reid, Ph.D., University Lecturer in Medical Genetics, Department of Medical Genetics, Univ. of Cambridge, UK.

    “Defining a Pathway that could be Targeted to Increase Age at Onset of HSP”

  • John K. Fink, MD

    John K. Fink, MD, Professor of Neurology, University of Michigan Medical Center, Ann Arbor, MI,

    “New Treatment Strategies for Primary Lateral Sclerosis”

  • Alan Mackay-Sim, Ph.D.

    Alan Mackay-Sim, Ph.D., Director, National Centre for Adult Stem Cell Research, Griffith University, Brisbane, Australia,

    “Finding Drugs to Treat Hereditary Spastic Paraplegia”

  • Andrew Grierson, PhD

    Andrew Grierson, PhD, Sheffield Institute for Translational Neuroscience, University of Sheffield, UK,

    “Development of Gene Therapy for treatment of Hereditary Spastic Paraplegia”

  • Kurt De Vos, PhD

    Kurt De Vos, PhD, Sheffield Institute for Translational Neuroscience, University of Sheffield, UK,

    “Development of Gene Therapy for treatment of Hereditary Spastic Paraplegia”

  • Mimoun Azzouz, PhD

    Mimoun Azzouz, PhD, Sheffield Institute for Translational Neuroscience, University of Sheffield, UK,

    “Development of Gene Therapy for treatment of Hereditary Spastic Paraplegia”

  • 2013

    Christina Fournier, M.D.

    Christina Fournier, M.D., Department of Neurology, Emory University, Atlanta, GA.
    Virginia Freer-Sweeney PLS Fellowship (two years) in collaboration with NEALS (Northeast ALS Consortium).

    “Upper Motor Neuron Disease Biomarkers”

  • 2012
    Andrew Grierson, Ph.D.

    Andrew Grierson, Ph.D., Senior Lecturer in Neuroscience, University of Sheffield, UK, and Kurt De Vos, Ph.D., Lecturer is Translational Neuroscience, University of Sheffield, UK, and Sheffield Institute for Translational Neuroscience,; and Ludo VanDen Bosch, Ph.D. Professor of Neurobiology, University of Leuven; Belgium Vesalius Research Center, Leuven, Belgium,

    “Development of a new therapeutic approach for treatment of hereditary spastic paraplegia.”

  • Tina H. Lee, Ph.D

    Tina H. Lee, Ph.D., Associate Professor, Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA,

    “Identification of potential compounds to treat SPG3A-associated HSP.”

  • Hiroshi Mitsumoto, MD, DSc.

    Hiroshi Mitsumoto, MD, DSc., Division Head, Wesley J. Howe Professor of Neurology, Columbia University College of Physicians and Surgeons, Columbia University, New York, NY,

    “Extensive biomarker and genetic analysis of bio-samples obtained from patients with clinically definite PLS, whose clinical and epidemiological features are well defined.”

  • 2011
    Paola Arlotta, Ph.D.

    Assistant Professor of Stem Cell and Regenerative Biology, Harvard University

    “Molecular mechanisms of corticospinal motor neuron dysfunction in HSP and PLS”

  • Melissa M. Rolls, Ph.D.

    Assistant professor, Biochemistry and Molecular Biology, Penn State University, University Park, PA

    “Function of spastin in axon regeneration: a new role for the HSP protein Spastin”

  • Xue-Jun Li, Ph.D.

    Assistant Professor, Health Science Center, Department of Neuroscience, University of Connecticut, Farmington CT

    “Elucidating the role of BMP signaling in HSP using patient-specific induced pluripotent stem cells”

  • John K, Fink, M.D.

    Professor, Department of Neurology, University of Michigan, Ann Arbor, MI,

    “Natural history of primary lateral sclerosis and hereditary spastic paraplegia: establishing parameters for clinical trials”

  • 2010

    Dong-Hui Chen M.D., Ph.D.

    Research Assistant Professor, Department of Neurology, University of Washington, Seattle, WA

    “Genome-wide detection of mutations in all genes to identify the cause of a new familial spastic paraplegia.”

  • Susan K. McConnell Ph.D.

    Susan B. Ford Professor of Humanities and Sciences, Department of Biological Sciences, Stanford University, Stanford, CA

    “Optimal transplantation strategies for the reconstruction of corticospinal circuitry in HSP and PLS.”

  • Teepu Siddique, M.D.

    Les Turner ALS Foundation/ Herbert C. Wenske Professor, Davee Department of Neurology and Clinical Neurosciences and Department of Cell and Molecular Biology, Director, Division of Neuromuscular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL

    “NTE-induced Upper Motor Neuron Degeneration in Primary Lateral Sclerosis.”

  • 2009

    Hiroshi Mitsumoto M.D., D.Sc.

    Wesley J. Howe Professor of Neurology, Director, Eleanor & Lou Gehrig MDA/ALS Center, The Neurological Institute, Columbia University College of Physicians and Surgeons, New York, NY

    “Multicenter Prospective PLS Natural History Study”

  • Elena Irene Rugarli, M.D.

    University of Cologne, Germany.

    “Exploring alternative functions of paraplegin, a protein involved in autosomal recessive and sporadic HSP.”

  • 2008

    Paola Arlotta, Ph.D.

    Assistant Professor of Stem Cell and Regenerative Biology, Harvard University

    “Molecular mechanisms of corticospinal motor neuron dysfunction in HSP and PLS”

  • Janine Kirby, Ph.D.

    Academic Neurology Unit, The University of Sheffield Medical School, Sheffield, United Kingdom

    “Elucidation of upper motor neuron vulnerability in Primary Lateral Sclerosis”


  • Yasushi Kisanuki, M.D.

    Department of Neurology, Ohio State University, Columbus, OH

    “Paraplegia in HSP Rat: Analysis and treatment”


  • Jeffrey Macklis M.D. D.HST.

    Massachusetts General Hospital – Harvard Medical School Center for Nervous System Repair, Boston, MA

    “Molecular-Genetic Controls over the Development, Connections, and Survival of Upper Motor Neurons”

  • 2007

    Peter W. Baas, Ph.D.

    Department: Neurobiology and Anatomy, Drexel University, Philadelphia, PA

    “Mechanistic Basis of SPG4-based Hereditary Spastic Paraplegia”

    Challenged the prevailing “loss of function” theory for how mutant SPG4/ Spastin causes HSP by showing that the defective protein expressed by this gene is actually toxic to neurons. Other proteins can perform the cellular function not being performed by defective Spastin protein. Published the results of his work in the February, 2008 issue of The Journal of Neuroscience, and the April, 2008 issue of the journal Molecular Biology of the Cell.

  • Bruce Horazdovsky, Ph.D.

    Department of Biochemistry & Molecular Biology and The Mayo Clinic Cancer Center, Associate Dean, Mayo Clinic College of Medicine Rochester, MN

    “Development of a cell culture system to analyze defects associated with Primary Lateral Sclerosis”

    Developed a differentiated and polarized human cell culture system to evaluate the function of the protein Alsin in the normal and disease states. This step was necessary to apply for a large NIH grant regarding the protein Alsin (mutations in the ALS2/ Alsin gene cause infantile onset PLS, HSP and ALS).

  • Stephen Zuchner, M.D

    Director, Center for Human Molecular Genetics, Miami Institute for Human Genetics, Leonard M. Miller School of Medicine, Miami, FL

    “Molecular and genetic analysis of the SPG31 gene REEP1″

  • 2006
    John K. Fink, M.D.

    Professor, Department of Neurology, University of Michigan, Ann Arbor, MI,

    “Natural history of primary lateral sclerosis and hereditary spastic paraplegia: establishing parameters for clinical trials”


  • Jeffrey Macklis M.D. D.HST.

    Massachusetts General Hospital – Harvard Medical School Center for Nervous System Repair, Boston, MA

    “Molecular-Genetic Controls over the Development, Connections, and Survival of Upper Motor Neurons”

  • Nina Tang Sherwood Ph.D.

    IGSP Scholar and Assistant Research Professor of Biology, Duke University, Durhan, NC

    “Understanding the ameliorative effects of temperature in fruit fly models of AD-HSP”

    Dr. Sherwood’s work for the SPF is ongoing. Results have not been published or made public.


  • Kendal S. Broadie, Ph.D.

    Professor of Neurobiology, Vanderbilt University, Nashville, TN

    “Mechanistic Interactions among Hereditary Spastic Paraplegia Genes”

  • 2005

    Kendal S. Broadie, Ph.D.

    Professor of Neurobiology, Vanderbilt University, Nashville, TN

    “Mechanistic Interactions among Hereditary Spastic Paraplegia Genes”

  • Peter Hedera, M.D.

    Assistant Professor, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN

    “Invertebrate model of Hereditary Spastic Paraplegia”

    Created a line of C. elegans (a microscopic worm) with HSP caused by mutations in their SGG6/ NIPA1 gene, and another line of these worms with HSP caused by knocking out their SPG2A/ Atlastin gene. Determined that HSP caused by mutations in the SPG6/ NIPA1 gene is associated with accumulation of misfolded NIPA1 protein, which triggers neuronal degeneration and programmed cell death. In a line of C. elegans with mutant SPG6/ NIPA1 genes and a mutation in another gene that causes the worms to be resistant to programmed cell death, observed that the disease course was slower and less severe. Published findings in the December, 2008 issue of the Journal of Neuroscience.


  • Jeffrey Macklis M.D. D.HST.

    Massachusetts General Hospital – Harvard Medical School Center for Nervous System Repair, Boston, MA

    “Molecular-Genetic Controls over the Development, Connections, and Survival of Upper Motor Neurons”

  • 2004
    Vincent T. Cunliffe, Ph.D.

    Centre for Developmental Genetics and Department of Neurology, University of Sheffield, Sheffield, United Kingdom

    “Modelling the neurodegenerative processes caused by mutation of the spg4 gene in zebrafish and development of strategies for pharmacological intervention”

    Discovered a crucial role for Spastin (defective Spastin causes the most common type of adult onset HSP) in promoting axon outgrowth in the zebrafish embryo. The discovery was published in the high profile journal Human Molecular Genetics, and the journal also included an image from the paper on the cover of the issue in which the article appeared, further enhancing the visibility of the research.

  • Jonathan D. Wood, Ph.D.

    Centre for Developmental Genetics and Department of Neurology, University of Sheffield, Sheffield, United Kingdom

    “Modelling the neurodegenerative processes caused by mutation of the spg4 gene in zebrafish and development of strategies for pharmacological intervention”

    Discovered a crucial role for Spastin (defective Spastin causes the most common type of adult onset HSP) in promoting axon outgrowth in the zebrafish embryo. The discovery was published in the high profile journal Human Molecular Genetics, and the journal also included an image from the paper on the cover of the issue in which the article appeared, further enhancing the visibility of the research.

  • Teepu Siddique, M.D.

    Les Turner ALS Foundation/ Herbert C. Wenske Professor, Davee Department of Neurology and Clinical Neurosciences and Department of Cell and Molecular Biology, Director, Division of Neuromuscular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL

    “NTE-induced Upper Motor Neuron Degeneration in Primary Lateral Sclerosis.”

  • 2003
    John K, Fink, M.D.

    Professor, Department of Neurology, University of Michigan, Ann Arbor, MI,

    “Natural history of primary lateral sclerosis and hereditary spastic paraplegia: establishing parameters for clinical trials”

  • Douglas Marchuk, Ph.D.

    Department of Molecular Genetics & Microbiology, Duke University, Durham, NC

    “A Mouse Model for Hereditary Spastic Paraplegia”

    Developed a line of mice into which the mutated, human gene KIF5A was incorporated. (Mutated KIF5A causes HSP.) These mice developed several symptoms consistent with human HSP. These mice were then cross-bred with another line of mice that had been developed by Dr. Larry Goldstein at the University of California, San Diego that had only one copy of the KIF5A gene. This was done to attempt to develop mice that developed more severe HSP-like symptoms and at an earlier age. By the end of the period of grant funding, those mice were too young to have developed symptoms.

"Science has come a long way in the past several years in discovering the cellular processes that are affected by PLS and HSP. I look forward to the day that we have a cure."

Mark Weber, Esq., chairman of the SPF Research Grant Committee.

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State of HSP Research:The Promise and the Reality by Allen Bernard

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