NurOwn (NCT03280056) was a landmark Phase 3 clinical trial evaluating autologous mesenchymal stem cell (MSC) therapy for amyotrophic lateral sclerosis, conducted by BrainStorm Cell Therapeutics. This trial represented one of the most advanced stem cell approaches for neurodegenerative disease, utilizing the patient's own cells that were engineered to secrete neurotrophic factors before being reintroduced into the body.
The trial completed in 2020 and generated important data on the safety and potential efficacy of stem cell therapy in ALS, while also providing insights into the challenges of cell-based approaches for neurodegenerative diseases. While primarily focused on ALS, the findings from NurOwn have implications for broader neurodegenerative disease research, including Parkinson's disease and other conditions where neurotrophic factor support may be beneficial.
| Attribute |
Value |
| NCT Number |
NCT03280056 |
| Phase |
Phase 3 |
| Status |
Completed (results published) |
| Sponsor |
BrainStorm Cell Therapeutics |
| Enrollment |
196 patients |
| Duration |
28 weeks treatment |
| Study Period |
2017-2020 |
| Locations |
US (multiple centers) |
| Randomization |
2:1 (active:placebo) |
| Delivery Route |
Intrathecal injection |
NurOwn utilizes a sophisticated autologous stem cell approach that represents one of the most advanced cell therapy platforms in neurodegeneration:
-
Cell Harvest
- Patient's own bone marrow is aspirated
- MSCs are isolated and expanded in culture
- Autologous cells avoid immune rejection concerns
-
Neurotrophic Factor Secretion
- Cells are cultured under proprietary conditions
- Induces secretion of multiple neurotrophic factors
- Cells become "MSC-NTF" cells (mesenchymal stem cells - neurotrophic factors)
-
Neurotrophic Factors Produced
- BDNF (Brain-Derived Neurotrophic Factor): Supports motor neuron survival and synaptic function
- GDNF (Glial Cell Line-Derived Neurotrophic Factor): Potent motor neuron protector
- HGF (Hepatocyte Growth Factor): Anti-inflammatory and neuroprotective properties
- VEGF (Vascular Endothelial Growth Factor): Supports neurovascular health and angiogenesis
- IGF-1 (Insulin-like Growth Factor): Promotes neuronal survival and metabolism
-
Delivery Method
- Intrathecal injection (into spinal canal)
- Allows direct access to cerebrospinal fluid circulation
- Cells migrate to areas of injury in the spinal cord and brain
The neurotrophic factors secreted by NurOwn cells work through multiple pathways:
-
Neurotrophic Support
- Provides growth factors directly to dying motor neurons
- Supports axonal sprouting and synaptic function
- Promotes neuronal survival in hostile microenvironment
-
Immunomodulation
- Reduces pro-inflammatory immune responses
- Modulates microglial activation
- Creates favorable microenvironment for neuron survival
- May reduce autoimmune components of neurodegeneration
-
Anti-Apoptotic Effects
- Secreted factors block programmed cell death pathways
- Protects remaining motor neurons from excitotoxicity
- Promotes anti-apoptotic signaling cascades
-
Potential Regeneration
- Some evidence of neural differentiation potential
- May replace lost support cells (oligodendrocytes)
- Could promote remyelination in affected pathways
- Design: Randomized, double-blind, placebo-controlled
- Randomization: 2:1 treatment:placebo
- Treatment Schedule: 3 injections (baseline, week 8, week 16)
- Follow-up: 28 weeks total treatment period
- Diagnosis: Definite or probable ALS (El Escorial revised criteria)
- Age: 18-60 years
- Disease Duration: ≤2 years from diagnosis
- Forced Vital Capacity: ≥60% predicted
- ALSFRS-R: ≥26 points at baseline
Key Inclusion:
- Diagnosis of sporadic or familial ALS
- Uprright walking capability (or assistive devices)
- Ability to undergo intrathecal injection
- Signed informed consent
Key Exclusion:
- Significant cardiac, hepatic, or renal disease
- Active infection
- Immunosuppressive therapy
- Prior stem cell therapy
Primary:
- Rate of decline in ALSFRS-R (Revised ALS Functional Rating Scale)
- Change from baseline to week 28
Secondary:
- Slow vital capacity (SVC) change
- Muscle strength (hand-held dynamometry)
- Quality of life (ALSAQ-40)
- CSF neurotrophic factor levels
- Safety and tolerability
The trial did not meet its primary endpoint of significant difference in ALSFRS-R decline rate between treatment and placebo groups. However, pre-specified subgroup analyses suggested potential benefits in certain patient populations.
- Mixed results across different measures
- Some positive trends in slower disease progression
- Safety profile was consistent with prior phases
- Elevated CSF neurotrophic factors in treatment arm
- Demonstrated successful cell engraftment and function
- Correlation between BDNF levels and clinical response observed
-
Cell Therapy Challenges
- Autologous cells show patient-to-patient variability
- Optimal dosing and timing remain unclear
- Delivery method affects distribution
-
Disease Complexity
- ALS involves multiple pathophysiological pathways
- Single-mechanism approaches may be insufficient
- Combination approaches may be needed
-
Trial Design Considerations
- Subgroup analyses can reveal hidden benefits
- Biomarker-driven enrichment strategies may improve signal detection
- Longer follow-up may be needed for cell therapies
While NurOwn targeted ALS, the platform has implications for:
| Disease |
Rationale |
Status |
| Parkinson's Disease |
GDNF supports dopaminergic neurons |
Preclinical |
| Multiple Sclerosis |
Immunomodulation, remyelination |
Preclinical |
| Alzheimer's Disease |
BDNF supports memory circuits |
Research |
| Spinal Cord Injury |
Neurotrophic support, regeneration |
Research |
¶ Competitive Landscape
Stem cell approaches for neurodegeneration:
| Approach |
Company |
Indication |
Stage |
| NurOwn |
BrainStorm |
ALS |
Phase 3 |
| CNS10-NPC-GDNF |
Neuralstem |
ALS |
Phase 1/2 |
| IT-Remedy |
CytoMed |
ALS |
Phase 1 |
| MSC therapy |
Various |
PD |
Preclinical |
-
Next-generation platforms
- Allogeneic "off-the-shelf" cell products
- Gene-modified cells for enhanced factor secretion
- Combination cell-gene approaches
-
Disease-specific optimization
- Different neurotrophic factor profiles for different diseases
- Engineered cells with enhanced survival and function
-
Delivery innovations
- Intravenous vs intrathecal comparison
- Direct CNS injection approaches
- Biomaterial encapsulation for sustained release