Research Progress
What is De Novo Hereditary Spastic Paraplegia- SPG4?
Hereditary spastic paraplegia (HSP), is a rare neurological disease that involves weakness and spasticity, which is stiffness of the legs. These symptoms get worse over time. Early in the disease, there may be mild trouble walking and stiffness. These symptoms typically get worse slowly until a cane, walker, or wheelchair is needed. Currently, there are no treatments to prevent, slow, or reverse HSP. SPG4 is the most common subtype of Hereditary Spastic Paraplegia. Typically a hereditary disease, however when the mutations are“de novo”, meaning they occurred spontaneously and were not passed from either parent, it is called De novo Hereditary Spastic Paraplegia. Currently, there is no cure for HSP SPG4. However, there are some exciting studies being conducted by the leading scientists and doctors that are aimed at finding a CURE.
Vamsi Koduri, father of Maurya Koduri made a short film- Maurya's Rare Odyssey which was the official selection at the Rare Disease Film Festival. Click the link below to watch this short film
Scientific Advisory Board for Maurya Koduri Foundation
Liang Oscar Qiang MD, Ph.D.
Assistant Professor
Co-Director, Center for Cellular and Molecular Neuroscience
Deputy Editor-in-Chief, Metabolic Brain Disease
Neurobiology and Anatomy Department
College of Medicine, Drexel University
Dr. Qiang leads a research laboratory at Drexel University that focuses on using human induced pluripotent stem cell (hiPSC) based technologies to develop in vitro and ex vivo cellular and tissue models. His lab's research is primarily focused on studying several neurodegenerative disorders including HSP. The primary objective of Dr. Qiang's research is to elucidate the underlying etiology and causative mechanisms of these disorders and identify new molecular targets for treatment therapies via gene therapy and small chemical compounds.
Darius Ebrahimi- Fakhari MD, Ph.D.
Assistant Professor of Neurology, Harvard Medical School
Director, Movement Disorders Program;
Boston Children's Hospital.
Dr. Ebrahimi-Fakhari is a board-certified Child Neurologist with special expertise in neurogenetic diseases, neurodegenerative diseases and movement disorders. He serves as the Director of the Movement Disorders Program at Boston Children's Hospital.
As a physician-scientist dedicated to patient-centered translational research, his goal is to facilitate clinical trial readiness and to develop molecular therapies. His clinical research covers gene discovery and natural history studies. In the lab, his team is developing platforms for high-throughput small molecule and genetic screens in patient-derived neurons to identify therapeutic targets for neurological disorders in children.
Current Research
Gene Therapy- AAV9 Project Overview
DNA (Deoxyribonucleic acid) is a molecule that stores genetic information. Genes are the pieces of genetic information that the cells use to make protein. Gene Therapy is the process of fixing the dysfunctional gene or in other words the faulty code in DNA is fixed. The dysfunctional gene or flawed mutation is removed, and a new healthy gene replaces the faulty one.
AAV9 is particularly effective as it can penetrate the blood-brain barrier and infect various cell types, including neurons, without triggering significant immune responses or harmful effects. This makes AAV9 a promising method for delivering normal copies of the SPAST gene to cells impacted by SPG4.
It’s estimated that in total, this project will cost $3M and we are doing everything we can to raise as much as we can to fund the research.
M1 Antibody
SPAST, the gene that is mutated in SPG4-HSP, produces two spastin proteins: M1 and M87. M87 is easily detectable with antibody tools, while M1 poses significant challenges for detection and study. The M1 antibody will serve multiple purposes, including assessing the effectiveness of Gene Therapy and ASO (Antisense oligonucleotide) therapy by determining if the AAV-driven vector or ASOs are reducing the accumulated mutant M1 protein in the spinal cord. This is crucial, as M1 is the problematic mutant protein that has been difficult to detect.
Additionally, a key purpose of the M1 antibody is to use it as a therapeutic agent, distinct from Gene Therapy and ASO therapy. The idea is to introduce the M1 antibody itself into the afflicted neurons so that the antibody will bind to the toxic mutant protein and block its toxicity.
The team at Drexel University, led by Dr. Peter Baas, is currently developing a new monoclonal antibody specifically targeting M1. Initial results are promising, and once the final purified antibody is available, it will allow researchers to detect and study M1 in unprecedented ways. This advancement could lead to M1 in body fluids being used as a biomarker for disease progression, a therapeutic option to counteract M1 toxicity in patients, and a standard for evaluating the success of ongoing gene therapy initiatives.
Registry and Natural History Study for Early Onset HSP
The Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia (HSP) is focused on gathering longitudinal clinical data as well as biological samples (skin and/or blood and/or saliva) from male or female patients who exhibited onset of HSP symptoms at 18 years old or younger with (1) a clinical diagnosis of hereditary spastic paraplegia and/or (2) the presence of variants in HSP related genes and/or be a relative of a person with such a diagnosis. Maurya is enrolled in this study.
The study contact is Darius Ebrahimi Fakhari, MD, Ph.D. from Boston Children's Hospital