Home Regenerative Health Education GABAergic Interneuron Cell Therapy for Drug-Resistant Epilepsy

GABAergic Interneuron Cell Therapy for Drug-Resistant Epilepsy

Hope for seizure-free, smiling days with Cell therapy
©Mindful Cells. Hope for seizure-free, smiling days with cell therapy

Estimated reading time: 4 minutes

Is it time to look for new cell therapy treatments for drug-resistant focal epilepsy?

A specialized type of cell as allogenic cell therapy product – “medial ganglionic eminence (MGE) pallial-type GABAergic interneurons.” Most importantly, GABAergic interneurons derived from human embryonic stem cells (hESCs) for treatment of drug-resistant focal epilepsy.

Most importantly, the mechanism of action of ‘GABAergic interneurons’ as a cell therapy product involves the secretion of gamma-aminobutyric acid (GABA) in the seizure-affected brain to balance glutamate and GABA signals. Consequently, it balances the excitation or reduced inhibition of neurons that causes epileptic signals.

Accordingly, preclinical studies have shown that interneuron cell therapy for focal epilepsy is safe and demonstrates the effective dose-dependent reduction in seizures. Above all, phase 1/2 clinical trial interim data on the efficacy of reducing seizures in patients with drug-resistant focal epilepsy is promising.

Epilepsy and drug resistance

Recurrent seizures eminent character of chronic neurological disorder. Sudden, brief disturbances in electrical activity in the brain cause seizures. Epilepsy affects people of all ages, but it is most common in children and older adults.

‘Drug-resistant epilepsy (DRE)’ a term used to describe epilepsy that is not controlled by anti-seizure medications (ASMs).

DRE is diagnosed when a person has failed to become seizure-free after trying two or more ASMs at appropriate doses and for an adequate period.

Indeed, structural causes associated with brain more commonly presents DRE.

Does cell therapy offer a new hope for drug-resistant epilepsy patients?

Drug-resistant epilepsy (DRE) accounts for one-third of people with epilepsy. A drug product must address the frequency of seizures, cognitive function, and associated life expectancy and sudden unexpected death in epilepsy (SUDEP). In the same vein, the regenerative cell therapy product NRTX-1001 is making significant progress in clinical development.

Cell therapy product NRTX-1001 for drug-resistant focal epilepsy

NRTX-1001 – a regenerative cell therapy product developed by Neuronal Therapeutics, US. NRTX-1001 is a “specific medial ganglionic eminence (MGE) pallial-type GABAergic Interneurons” developed using human embryonic stem cell lines.

Manufacturing of cell therapy product – MGE pallial-type GABAergic Interneurons NRTX-1001

The hESC seed cell bank preparation and evaluation for cell therapy manufacturing done according to ICH Q5D

NRTX-1001 a cell therapy product manufactured using current Good Manufacturing Practices (cGMP)-grade hESCs from an approved cell line listed in the NIH hESC registry.

  • Genetic stability using karyotyping analysis by G-banding and single nucleotide polymorphism (SNP) arrays. 
  • Safety assessment done using sterility testing, mycoplasma, and adventitious agents.
  • Pluripotency confirmed by Oct4, Nanog, and TRA-1-60 expression and in vitro differentiation, and in vivo teratoma formation.
  • Changes in the number of copies of genes (Copy number variations CNVs) and long stretches of DNA that are the same on both copies (ROHs). 

The hESC seed bank specifically differentiated to MGE pallial-type GABAergic interneurons and cryopreserved according to Neurona Therapeutics’ in-house protocols.

Potency of the GABAergic interneurons tested using single cell RNA sequencing, in vitro migration, GABA secretion, and CNV and ROHs.

Proof-of-concept evaluation of a cell therapy for drug-resistant mesial temporal lobe epilepsy (MTLE)

The therapy involved the transplantation of cryopreserved, post-mitotic, MGE pallial-type GABAergic interneurons derived from hESCs into a mouse model of chronic MTLE.

The transplanted GABAergic interneurons

  • Effectively suppressed mesiotemporal seizures, with most animals becoming seizure-free and surviving longer.
  • Integrated into the local circuitry,
  • Persisted long-term, and
  • It significantly reduced dentate granule cell dispersion, a pathological feature of MTLE.
  • The therapeutic effects were dose-dependent, and no adverse effects observed.

Dosage and administration of GABAergic interneuron cell therapy product NRTX-1001 for focal epilepsy

GABAergic interneuron cell therapy product administered as a one-time dose into the epileptic region of the brain. The clinical trial includes immunosuppression in the first year. The five subjects in the first cohort of the clinical trial received a one-time administration of GABAergic interneurons along with immunosuppression. The immunosuppression is intended to promote the integration and long-term persistence of GABAergic interneurons in the body.

The intervention in this clinical trial involves a single stereotactic intracerebral administration of interneurons that secrete the inhibitory neurotransmitter GABA.

The clinical study consists of two stages.

In Stage 1, there is an open-label, single-arm, sequential dose escalation where up to Ten subjects received the GABAergic interneurons, NRTX-1001.

In Stage 2, there is a parallel, randomized, 2-arm, sham-controlled study. Up to 20 subjects receive the experimental treatment (GABAergic interneurons, NRTX-1001), and ten subjects receive a sham comparator. The sham comparator involves a procedure that mimics the administration without actually delivering the cells.

Author opinion

All things considered, the impact of GABAergic interneuron cell therapy on quality of life and life expectancy with epilepsy is promising.

GABAergic interneurons have the potential to improve quality of life, and here is why

  • For instance, reduced seizure frequency and severity significantly improve quality of life.
  • In addition, integration into the brain and balancing excitatory and inhibition signals by GABA may improve cognitive function.
  • Subsequently, GABAergic interneuron cell therapy may help to reduce the risk of SUDEP by decreasing the frequency and severity of seizures.


Cell therapy is a promising new treatment for drug-resistant focal epilepsy. Early clinical trial data from Neurona therapeutics NRTX-1001 GABAergic interneuron cell therapy are encouraging. Further clinical development is underway to establish the long-term safety and efficacy of cell therapy.



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