Learn more about current projects we support and
how you can help fund the research necessary for a cure.
Cure SPG4 Foundation is actively funding several research projects. We have teamed up with leading experts in SPG4, gene therapy, and upper motor neuron diseases. 100% of donations to the Cure SPG4 Foundation will go directly towards research programs aimed at finding a cure for SPG4 Hereditary Spastic Paraplegia. Donations are critical to initiate new research and to keep promising research projects moving forward.
Recent advancements in gene therapy for genetic diseases have given hope to the SPG4 community. Gene therapy goes beyond treating symptoms. With gene therapy, the faulty code in the DNA is fixed. The flawed mutation is removed and a new, healthy gene replaces it. Through the collaboration of Dr. Miguel Sena-Esteves at UMass Medical School and Dr. Peter Baas and Dr. Liang Oscar Qiang at Drexel University, we are excited to share that work has begun on AAV gene therapy for SPG4 Hereditary Spastic Paraplegia.
A healthy copy of the patient's defective gene is loaded into a virus that has been stripped of its own DNA.
Trillions of viruses, each containing a healthy copy of the gene, are injected into the patient's spinal fluid.
The viruses bind to cells in the patient's spinal cord and brain and deliver healthy gene's to the cell's nucleus.
Project Status as of September 2022
A number of mice have been injected with either the SPAST vector or the control by the Baas Laboratory at Drexel University College of Medicine; preliminary data from injections is promising
Four additional AAV9 vectors have been generated by the Sena-Esteves Laboratory at UMass Medical School for further testing
Monthly breeding/injections will continue in order to obtain more robust and conclusive data
Donations to Cure SPG4 Foundation are much appreciated and needed to help expand and further expedite the SPG4 gene therapy project
Project Status as of January 2022
Two AAV9 vectors for SPG4 have been created by the Sena-Esteves Laboratory at UMass Medical School
Both vectors are currently being tested on SPG4 animal models by the Baas Laboratory at Drexel University College of Medicine
Initial data is expected by year end 2022
The Basics of
Gene therapy is the introduction, removal or change in genetic material—specifically DNA or RNA—into the cells of a patient to treat a specific disease. The transferred genetic material changes how a protein—or group of proteins—is produced by the cell.
Dr. Hande Ozdinler, from Northwestern University, is an expert in upper motor neuron cellular biology. Her team recently reported on a small molecule, known as NU-9, which is showing great promise in the treatment of upper motor neuron diseases. The compound is thought to improve the structural stability of the cell through the endoplasmic reticulum. Because upper motor neurons display early degeneration in patients with the SPG4 mutation, it is of great interest to find out whether NU-9 could also improve the health of upper motor neurons that become diseased due to SPG4. Cure SPG4 Foundation has initiated a collaboration with the Ozdinler Lab at Northwestern University, Feinberg School of Medicine, to find the answer to this important question.
Project Status as of March 2022
In vitro studies of NU-9 for SPG4 were initiated in 2021 and have shown promising results
In vivo studies are currently underway to determine efficacy of NU-9 in SPG4 animal models
Project will be funded each quarter in 2022. Cure SPG4 Foundation greatly appreciates continued donations to keep this project moving forward.
Peter W. Baas, PhD
Peter W. Baas earned his PhD from Michigan State University in 1987, completed his postdoctoral work at Temple University in 1990, and then took a faculty job at University of Wisconsin. In 2000, he moved to Drexel University where he continues today as Professor of Neurobiology and Anatomy. He is also Director of the Graduate Program in Neuroscience. Dr. Baas is a cellular neuroscientist who focuses his research on neurodevelopmental mechanisms and neurodegenerative disorders related to architectural structures in nerves called microtubules. He became interested in Hereditary Spastic Paraplegia because the gene that is mutated in the majority of cases encodes for a microtubule-related protein called spastin. For roughly 15 years, he has studied Hereditary Spastic Paraplegia using a number of different experimental systems. Most recently he has developed a mouse model that recapitulates the symptoms of the disease and does so by expressing human spastin bearing one of the mutations found in patients. Dr. Baas is dedicated to identifying mechanism-based therapies for the disease that will prevent and hopefully correct that debilitating symptoms suffered by patients of all ages and backgrounds.
Miguel Sena-Esteves, PhD
Miguel Sena-Esteves, PhD, is an Associate Professor in the Neurology Department and Horae Gene Therapy Center at UMass Medical School. His laboratory focuses on AAV capsid engineering for in vivo gene transfer to CNS and other tissues, as well as gene therapies for various inherited diseases including lysosomal storage diseases, HD, ALS, neurofibromatosis type 1 (NF1), and muscular dystrophies. He is part of a team of researchers and physicians that developed AAV gene therapies for GM2 gangliosidosis (Tay-Sachs and Sandhoff diseases), and GM1 gangliosidosis both currently being tested in phase I/II clinical trials.
Liang Oscar Qiang, MD, PhD
Dr. Liang Oscar Qiang is an Assistant Professor in the Neurobiology and Anatomy Department at Drexel University. He received his MD from Nantong Medical College, China and his PhD from Drexel University. Qiang Lab is focusing on using isogenic human induced pluripotent stem cell (hiPSC) derived CNS models as well as transgenic mouse models, both of which contain various types of spastin (SPAST, SPG4) mutations, to elucidate the etiology of SPG4 based Hereditary Spastic Paraplegia (HSP-SPG4). Based on his previous studies on HSP-SPG4, Dr. Qiang posits that gain-of-toxicity and loss-of-function, both resulting from mutations of SPAST, may contribute to the disease pathogenesis via distinct underlying mechanisms. Preclinical therapeutic interventions arising from evidence which was gathered in both model systems are also being put into test.
Hande Ozdinler, PhD
Hande Ozdinler, PhD, is leading a laboratory at Northwestern University Feinberg School of Medicine, that has a goal to understand the cellular and molecular basis of selective neuronal vulnerability. Dr. Ozdinler and her team primarily focus on upper motor neurons, which are the neurons that are important for the initiation and modulation of voluntary movement. Upper motor neuron degeneration is a key feature in many motor neuron diseases, such as hereditary spastic paraplegia (HSP). Currently, there are no effective treatment strategies for any of the motor neuron diseases, and the upper motor neuron component is vastly ignored. For these reasons, Dr. Ozdinler’s research is exceptionally important, urgent, and timely. The Ozdinler Laboratory generated the first reporter line for upper motor neurons, which allows for the development of novel drug discovery platforms that incorporate upper motor neuron health in decision-making prior to moving into clinical trials. This advancement has been a game changer, especially for diseases that are characterized by progressive upper motor neuron loss. Investigations of the Ozdinler Lab will improve success rates of clinical trials, and will help identify novel compounds that improve the health of upper motor neurons.
Emanuela Piermarini, PhD
Emanuela was born and raised in a small town close to Rome, Italy. She earned her PhD degree in Biochemistry and Molecular Biology at University of Rome "Tor Vergata" and Bambino Gesù Children's Research Hospital IRCCS in 2016. During her PhD training, she studied the role of oxidative stress in the context of Friedreich's ataxia, a rare neurodegenerative disease affecting children. She joined Drs. Peter Baas and Liang Qiang laboratories as a Postdoc and recently as a Research Associate. Dr. Piermarini works primarily on the Hereditary Spastic Paraplegia (HSP) gene therapy project. She uses both behavioral and anatomical approaches to characterize the disease progression and mechanisms of neurodegeneration underlying the disease. With this information, she is able to help develop potential therapeutic approaches.
Our Research Partners
You can help fund research today.
It is critical for affected individuals, their families, and generous donors to help fund the research necessary to help find a cure. Donations to the Cure SPG4 Foundation go directly towards gene therapy research and other programs like it.