by Central nervous system (CNS) disorders, including neurodegenerative diseases, neurological disorders, and psychiatric conditions, impose immense suffering worldwide. Current treatment options for CNS disorders are limited and mostly manage symptoms rather than cure the underlying cause. Gene and cell therapies offer promising alternatives that can potentially slow, stop or even reverse the progression of these debilitating conditions. This article explores some of the latest advancements in gene and cell therapies targeting CNS disorders.
Promising new gene therapies
Gene therapy aims to treat diseases by delivering healthy copies of genes into cells to compensate for abnormal genes. For CNS disorders, gene therapies show potential in neurodegenerative diseases like Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS).
In PD, degeneration of dopamine-producing neurons in the substantia nigra leads to motor impairments. Researchers at the University of California are testing a gene therapy that delivers the gene for an enzyme called aromatic L-amino acid decarboxylase (AADC) directly into the brain using an adeno-associated virus (AAV) vector. AADC helps produce dopamine from levodopa. Preliminary results found the therapy was safe and improved motor functions in PD patients for over a year following a single treatment.
ALS is characterized by progressive motor neuron death. Researchers reported positive results from a Phase 1 clinical trial of an intrathecal Gene and Cell Therapies Targeting CNS Disorders delivering the human insulin-like growth factor 1 (IGF-1) gene to motor neurons. IGF-1 promotes motor neuron survival and outgrowth of neuronal connections. The therapy was well-tolerated and slowed disease progression in some patients for over 18 months after a single treatment.
Groundbreaking cell therapies
Cell therapies aim to replace diseased or dead cells with healthy ones. For neurodegenerative conditions with defined cell loss, like Huntington’s disease, cell therapies could restore lost functions.
Researchers at Stanford University are testing a novel stem-cell therapy for Huntington’s disease. In this disease, specific brain regions gradually degenerate due to the death of medium spiny neurons. The researchers program skin cells from Huntington’s patients into induced pluripotent stem cells, then into medium spiny neuron-like cells. Early results found no safety concerns after implanting these neuronal progenitor cells directly into the brains of monkeys. The implanted cells differentiated normally and showed potential to rewire damaged neural circuits.
Targeting psychiatric conditions
Some psychiatry disorders may also benefit from gene and cell therapies targeting specific brain circuits and pathways implicated in their pathologies.
For treatment-resistant depression, researchers are investigating therapies that increase the brain’s natural antidepressant pathways. Gene and Cell Therapies Targeting CNS Disorders One approach uses gene therapy to boost brain-derived neurotrophic factor (BDNF) signaling. BDNF promotes neuronal growth and plays a key role in regulating mood. Early-stage trials found injecting a plasmid carrying the BDNF gene directly into the brain increases BDNF levels and improves depression symptoms for months.
Another promising line of research focuses on replacing glial cells for schizophrenia. Accumulating evidence points to glial dysfunction in the prefrontal cortex and hippocampus contributing to cognitive and emotional symptoms in schizophrenia. Scientists are experimenting with transplanting interneuron progenitor cells generated from patients’ own induced pluripotent stem cells. It’s hoped new glial cells may shore up vulnerable neural circuits and support improved mental functions.
Challenges and the road ahead
While gene and cell therapies hold immense promise, several challenges remain in effectively translating these approaches to the clinic. Precise delivery of therapeutic agents to specific brain regions, long-term survival of transplanted cells, determining optimal dosing, and managing immune responses require further refinement. Large, well-controlled clinical trials are also still needed to establish clear safety and efficacy profiles.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
