News Release 

Realizing the potential of gene therapy for neurological disorders

Advances in gene therapy may aid future treatments of Alzheimer's disease, Parkinson's disease, and more

Society for Neuroscience

CHICAGO -- Promising findings from preclinical animal studies and postmortem human brain data show the potential of gene therapy for treating currently incurable neurological disorders. The findings were presented at Neuroscience 2019, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news about brain science and health.

Gene therapy is an experimental technique that involves altering specific genes to treat or prevent disease. Typically, an inactivated virus is used to carry the genetic cargo into cells. Researchers might replace a mutated gene with a healthy copy of the gene, turn off a disease-causing gene, or add a new gene to the body to help fight a disease. Gene therapy is a promising treatment for a number of currently incurable neurological diseases, such as Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease.

Today's new findings show that:

  • A promising new therapeutic approach reprograms glial cells into motor neurons in vivo to restore lost motor functions in a mouse model of amyotrophic lateral sclerosis (Gong Chen, Penn State University).
  • Brain delivery of a small, engineered antibody that specifically recognizes toxins present in the brains of Alzheimer's disease patients prevents brain damage and memory loss in preclinical models of the disease (Sérgio Ferreira, Federal University of Rio de Janeiro).
  • Minimally invasive methods of treating neurological disease may become possible with the use of harmless viruses modified to deliver treatments to the brain in mice (Sophie Mathieson, University of Otago, New Zealand).
  • Gene delivery to the central nervous system in two patients with advanced Parkinson's disease resulted in long-term gene expression and evidence of targeted effects on dopamine neuron (Jeff Kordower, Rush University).
  • A novel method can produce neural progenitor cells in larger quantities for gene therapy than previous methods (Clive Svendsen, Cedars-Sinai).

"Gene therapy holds the promise to transform the lives of patients with incurable neurological diseases," said Jeff Kordower, PhD, a professor at Rush University who studies aging and neurodegenerative disease. "The research presented today represents important and exciting steps toward being able to prevent and treat disorders that currently have no cure, such as Parkinson's disease and Alzheimer's disease."

This research was supported by national funding agencies including the National Institutes of Health and private funding organizations. Find out more about gene therapy on BrainFacts.org.

Related Neuroscience 2019 Presentation
Roundtable: Gene Therapy in Neurological Diseases
Wednesday, Oct. 23, 8:30 - 11:00 a.m., Room N230B

Gene Therapy Press Conference Summary

  • Gene therapy holds great potential for treating currently uncurable neurological diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.
  • Preclinical animal studies are essential for refining gene therapy methods and learning more about the most effective ways to deliver genes to the central nervous system.

A Gene Therapy Approach to Directly Reprogram Reactive Astrocytes Into Functional Motor Neurons in SOD1G93A ALS Mouse Model
Gong Chen, guc2@psu.edu, Abstract 475.10

  • In vivo cell conversion, a technology that uses gene therapy to reprogram glial cells into functional neurons in the central nervous system, has shown promise in mouse models of Alzheimer's disease and other brain disorders.
  • Researchers have now identified several regulatory genes that can convert glial cells into motor neurons in the spinal cord in a mouse model of amyotrophic lateral sclerosis (ALS), offering a possible therapeutic approach to restore lost motor function.
  • Ongoing studies are testing different genes to improve cell conversion efficiency and identify the optimal time window for the treatment of ALS.

Neuronal Expression of Nusc1, a Single-Chain Variable Fragment Antibody Against Abeta Oligomers, Protects Synapses and Rescues Memory in Alzheimer's Disease Models
Sérgio Ferreira, ferreira@bioqmed.ufrj.br, Abstract 447.13

  • A small, engineered antibody called NUsc1 specifically recognizes a type of toxin that accumulates in the brains of Alzheimer's patients and that is thought to impair synapse function, learning, and memory.
  • Gene therapy delivery of NUsc1 protected against these toxins in cultured neurons and improved memory in a mouse model of Alzheimer's disease.
  • The same gene delivery system produced NUsc1 antibodies in postmortem human brain tissue.
  • NUsc1 may represent a novel tool for gene therapy aimed at preventing or reversing neuronal damage and memory loss in Alzheimer's disease.

Investigating Enhanced Gene Transfer to the Mouse Central Nervous System Using Modified Viral Vectors
Sophie. N. Mathieson, matso768@student.otago.ac.nz, Abstract 175.13

  • The blood-brain barrier helps protect the brain and spinal cord from outside influences, but largely prevents bloodstream delivery of therapeutic molecules to treat neurological diseases.
  • Adeno-associated viruses can be modified to be more effective at crossing the blood-brain barrier in mice, a step toward minimally invasive brain-targeted gene therapy.
  • Future work will assess a modified adeno-associated virus in a preclinical trial for the treatment of a mouse model of Alzheimer's disease.

Long-term Post-Mortem Studies Following Neurturin Gene Therapy in Advanced Parkinson's Disease
Jeff Kordower, Jeffrey_Kordower@rush.edu, Abstract 383.05

  • Neurturin is a molecule that has been shown to markedly enhance dopaminergic neuronal survival and behavioral function in animal models of Parkinson's disease.
  • Two human patients with advanced Parkinson's disease received gene therapy to deliver the neurturin gene to brain regions affected by the disease.
  • Postmortem studies conducted eight and 10 years later revealed persistent expression of the delivered gene and evidence of continuing function of the remaining dopamine neurons; however, the changes observed were likely not sufficient to provide significant benefits.

Scalable cGMP Compliant Expansion of Human Fetal and iPSC Derived Neural Progenitor Cells
Clive Svendsen, Clive.Svendsen@cshs.org, Abstract 475.13

  • Scientists have developed a novel method for growing neural progenitor cells for use in the treatment of neurodegenerative diseases.
  • Neural progenitor cells produced with this new method were stable for up to three months when transplanted into the spinal cords of rats.
  • This new method will allow expansion of neural progenitor cultures to the larger scales necessary for later-stage clinical trials and full therapeutic production.

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About the Society for Neuroscience

The Society for Neuroscience is the world's largest organization of scientists and physicians devoted to understanding the brain and nervous system. The nonprofit organization, founded in 1969, now has nearly 37,000 members in more than 90 countries and over 130 chapters worldwide.

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