NRTX-1001 Neural Cell Therapy for Epilepsy

Recruiting at 29 trial locations

Overseen By Sumeet Vadera, MD, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Neurona Therapeutics

Must be taking: ASDs

Disqualifiers: Neurologic disease, Immunodeficiency, Psychiatric disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

58 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if injecting special brain cells into the brain can help patients with hard-to-treat epilepsy. The new cells release a calming chemical to reduce seizures. Patients will also take medicines to prevent their bodies from rejecting the new cells.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that participants must be on stable doses of approved anti-seizure drugs for at least one month before joining.

What data supports the effectiveness of the NRTX-1001 treatment for epilepsy?

Research shows that stem cell therapies, like those using neural stem cells, have potential in treating epilepsy by integrating into brain circuits and possibly reducing seizures. Additionally, studies on similar stem cell treatments have shown promise in reducing seizure frequency in drug-resistant epilepsy. ^{1 2 3 4 5}

How is the NRTX-1001 treatment different from other epilepsy treatments?

NRTX-1001 is unique because it involves neural cell therapy, using neural stem cells that can integrate into the brain's circuitry to potentially repair or replace malfunctioning neurons, unlike traditional anti-epileptic drugs that mainly focus on suppressing seizures. ^{2 4 6 7 8}

Research Team

John Hixson, MD

Principal Investigator

Neurona Therapeutics

Eligibility Criteria

This trial is for adults aged 18 to 65 with drug-resistant mesial temporal lobe epilepsy. Participants must have a history of focal seizures, be on stable epilepsy medication doses, and have confirmed seizure focus in one temporal lobe. They should not have attempted suicide in the past year, severe psychiatric disorders, pregnancy or breastfeeding status, progressive neurological diseases other than epilepsy, significant medical conditions that impair participation, immunodeficiency or chronic intracranial devices.

Inclusion Criteria

I have been on a stable dose of my seizure medication for at least a month.

I have had an average of 2 or more seizures every month for the last 6 months.

I still have seizures despite trying at least 2 different seizure medications.

Exclusion Criteria

Your MRI shows a possible cancerous growth.

My epilepsy is caused by a progressive neurological condition.

You tried to harm yourself in the last year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single stereotactic intracerebral administration of inhibitory nerve cells (NRTX-1001) and take immunosuppressive medicines for 1 year

1 year

Follow-up

Participants are monitored for safety, tolerability, neural cell viability, local inflammation, and effects on epilepsy symptoms

2 years

Regular MRI scans and assessments

Long-term follow-up

Participants are followed for an additional 13 years with quarterly phone contact and annual visits

13 years

Quarterly phone contact, annual visits

Treatment Details

Interventions

• NRTX-1001
• Sham Comparator

Trial Overview The study tests NRTX-1001 neural cell therapy's safety and effectiveness against placebo (sham comparator) in reducing seizure frequency. It involves a single stereotactic injection of inhibitory nerve cells directly into the brain of subjects with unilateral mesial temporal lobe epilepsy who haven't responded to at least two anti-seizure drugs.

Participant Groups

Group I: NRTX-1001 (Phase 2) Experimental Treatment 1 Intervention

Up to 20 subjects

Group II: NRTX-1001 (Phase 1) Experimental Treatment 1 Intervention

Up to 28 subjects

Group III: Sham Comparator(Phase 2) Placebo Group 1 Intervention

Up to 10 subjects.

Who Is Running the Clinical Trial?

Neurona Therapeutics

Lead Sponsor

Trials

2

Recruited

50+

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

Findings from Research

The 2018 NINDS workshop emphasized the urgent need for therapies that can prevent epilepsy (antiepileptogenesis) and modify the disease, highlighting the complexities in trial design, such as timing of intervention and appropriate dosing.

Recent trials, like those using vigabatrin for children with tuberous sclerosis, illustrate the challenges and potential strategies for developing effective treatments, while also addressing regulatory hurdles that impact the progress of these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiepileptogenesis and disease modification: Clinical and regulatory issues. French, JA., Bebin, M., Dichter, MA., et al.[2022]

In a Phase I clinical trial involving patients with drug-resistant epilepsy, the use of autologous mesenchymal stem cells (MSC) was well tolerated and did not lead to severe adverse effects, indicating a good safety profile for this therapy.

The MSC therapy showed promising efficacy, with 30% of patients achieving seizure remission and 50% becoming responders to anti-epileptic drugs, compared to only 17% in the control group, highlighting the potential of MSC as a treatment option for epilepsy resistant to conventional medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of refractory epilepsy patients with autologous mesenchymal stem cells reduces seizure frequency: An open label study. Hlebokazov, F., Dakukina, T., Ihnatsenko, S., et al.[2018]

Out of 101 registered trials for pediatric drug-resistant epilepsy, 32% focus on neurotechnological interventions, with 46% of those specifically investigating methods like vagus nerve stimulation and deep brain stimulation.

The study highlights a gap between the current clinical research on neurotechnology for pediatric epilepsy and its practical application, emphasizing the need for timely evidence to support the adoption of these interventions in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Research Landscape of Pediatric Drug-Resistant Epilepsy. Kaal, KJ., Aguiar, M., Harrison, M., et al.[2021]

Neural stem cells and progenitors (NSC/NPs) show great potential for treating epilepsy due to their ability to integrate into brain circuitry and restore lost functions, as highlighted by various studies in animal models.

While there are promising results regarding the use of NSC/NPs for neuro-restorative therapy, significant challenges remain that must be overcome before these therapies can be applied in clinical settings for epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cells as a potential therapy for epilepsy. Roper, SN., Steindler, DA.[2022]

Transplanting embryonic GABAergic interneurons into the epileptic brain shows promise in stopping seizures by enhancing inhibition in affected areas, making it a potential treatment for difficult-to-treat epilepsy.

Recent research focuses on isolating and transplanting these cortical interneuron precursors from both mouse and human sources, although several challenges remain before this therapy can be widely used in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interneuron Transplantation as a Treatment for Epilepsy. Hunt, RF., Baraban, SC.[2018]

Approximately 30% of epilepsy patients do not respond to existing antiepileptic drugs, highlighting the need for new treatment strategies.

Cell-based therapies show promise as a novel approach to treat epilepsy by either producing natural anticonvulsants or repairing damaged neuronal circuits, potentially offering new hope for patients with drug-resistant epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Commentary: the prospect of cell-based therapy for epilepsy. Kriegstein, AR., Pitkänen, A.[2021]

Hematopoietic Stem Cell (HSC) therapy shows potential as a novel treatment for epilepsy, particularly in cases where traditional pharmacotherapy is ineffective, as seen in refractory epilepsy.

While pre-clinical studies indicate promising results for HSC therapy in promoting neuroprotection and neuronal regeneration, clinical effects remain marginal, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review on Hematopoietic Stem Cell Treatment for Epilepsy. Ghanta, MK., Merchant, N., Bhaskar, LVKS.[2022]

The study successfully induced differentiation of embryonic stem cell-derived neural stem/progenitor cells into GABAergic neurons, which were then transplanted into epileptic mice, showing significant recovery from seizures compared to the control group.

Transplanted GABAergic neurons led to substantial re-innervation in the hippocampus and reduced seizure activity, indicating that these cells could be a promising therapy for treating difficult-to-manage epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seizure suppression in amygdala-kindled mice by transplantation of neural stem/progenitor cells derived from mouse embryonic stem cells. Shindo, A., Nakamura, T., Matsumoto, Y., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Antiepileptogenesis and disease modification: Clinical and regulatory issues. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of refractory epilepsy patients with autologous mesenchymal stem cells reduces seizure frequency: An open label study. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

The Clinical Research Landscape of Pediatric Drug-Resistant Epilepsy. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Stem cells as a potential therapy for epilepsy. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Interneuron Transplantation as a Treatment for Epilepsy. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Commentary: the prospect of cell-based therapy for epilepsy. [2021]

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

A Review on Hematopoietic Stem Cell Treatment for Epilepsy. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

Seizure suppression in amygdala-kindled mice by transplantation of neural stem/progenitor cells derived from mouse embryonic stem cells. [2019]