How Stem Cells Are Pioneering New ALS Treatments
A revolutionary approach in the fight against a relentless disease
For those battling amyotrophic lateral sclerosis (ALS), the search for effective treatments has been fraught with challenges. But on the frontlines of research, a powerful combination is emerging: mesenchymal stem cells (MSCs) engineered to produce insulin-like growth factor 1 (IGF-1). This innovative strategy aims not only to protect vulnerable motor neurons but to create a nurturing environment that could slow—and potentially alter—the course of this devastating disease.
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a progressive neurodegenerative disorder that primarily affects the nerve cells responsible for controlling voluntary muscle movement 1 . With an annual incidence of 0.6 to 3.8 per 100,000 people, ALS may be considered rare, but its impact is devastating 1 . The disease leads to the gradual degeneration and death of motor neurons, resulting in muscle weakness, atrophy, and eventually paralysis 5 .
Most cases (90%) occur sporadically with no known cause, while only 5-10% are familial, showing an autosomal dominant pattern 1 . Regardless of the type, the prognosis is grim: most patients survive only 2 to 5 years from symptom onset, typically succumbing to respiratory failure as diaphragm control is lost 1 5 .
The complexity of ALS lies in its multiple proposed pathological mechanisms, which include glutamate excitotoxicity, oxidative stress, mitochondrial dysfunction, and neuroinflammation 5 . This complexity is why single-target therapies have largely failed to significantly alter disease progression.
Stem cell therapy represents a paradigm shift in how we approach ALS treatment. Unlike traditional drugs that typically target a single pathway, stem cells offer the potential to address multiple aspects of the disease simultaneously 2 .
They secrete growth factors and cytokines that support neuronal survival and health 5 .
Among various stem cell types, mesenchymal stem cells (MSCs) have emerged as particularly promising candidates. These are adult stem cells that can be obtained from various sources, including bone marrow, adipose tissue, and umbilical cord tissue 5 .
MSCs are not believed to directly replace dead motor neurons—a formidable challenge given the need to form proper connections with muscles. Instead, they primarily function as supportive players, creating a protective microenvironment that helps preserve remaining motor neurons 2 . As one study explained, stem cells "adopt a supportive role by providing a nurturing and neuroprotective microenvironment" for diseased motor neurons 2 .
Enter insulin-like growth factor 1 (IGF-1), a naturally occurring protein that plays a crucial role in neuronal development, survival, and function. IGF-1 promotes the growth and differentiation of neurons and supports synaptic formation and plasticity—the very processes compromised in ALS.
A 2025 study identified a single nucleotide variant in the promoter of IGFBP7 associated with reduced IGFBP7 levels in the brain and an ALS "reversal" phenotype 8 .
The connection between IGF-1 and ALS has gained substantial scientific backing. A 2025 study identified a single nucleotide variant in the promoter of IGFBP7 (a protein that binds to IGF-1) which was associated with reduced IGFBP7 levels in the brain and an ALS "reversal" phenotype 8 . This crucial finding suggests that modulating the IGF pathway could have therapeutic potential in ALS.
Further evidence comes from analyses showing increased IGFBP7 protein in ALS patients' blood and elevated IGFBP7 mRNA levels in their spinal cords and iPSC-derived motor neurons compared to healthy controls 8 . These findings collectively position the IGF-1 pathway as a compelling therapeutic target.
Recognizing the individual potentials of both MSCs and IGF-1, researchers have pioneered an innovative strategy: genetically modifying MSCs to overexpress IGF-1. This approach aims to create a sustained, localized delivery system for this protective factor directly to the vulnerable motor neurons.
The rationale is powerful: rather than administering IGF-1 systemically—which poses challenges in reaching the central nervous system and may cause side effects—the engineered MSCs serve as biological factories that produce IGF-1 exactly where it's needed most. When transplanted into the spinal cord or delivered via other routes, these modified cells can continuously secrete IGF-1 while simultaneously providing the other beneficial effects native to MSCs.
Preclinical studies have demonstrated that this approach can delay disease onset, slow progression, and extend survival in animal models of ALS, providing the foundation for translation to clinical applications.
The progress in MSC and IGF-1 research has been powered by sophisticated laboratory techniques that allow scientists to model and study ALS in unprecedented detail. The following toolkit highlights key resources driving this innovative field:
| Research Tool | Function and Application |
|---|---|
| Induced Pluripotent Stem Cells (iPSCs) 3 6 | Created from patient skin or blood samples, these cells can be differentiated into motor neurons, providing a personalized model for studying ALS mechanisms and testing treatments. |
| Mesenchymal Stem Cells (MSCs) 5 | Sourced from bone marrow or other tissues, these are the therapeutic agents often genetically modified to produce protective factors like IGF-1. |
| SOD1 Mouse Models 5 | The primary animal model for ALS research, these mice express a mutated human SOD1 gene and replicate key aspects of human disease progression. |
| Differentiation Protocols 5 | Specific chemical cocktails and culture conditions that direct stem cells to become specialized cells, such as motor neurons or supportive astrocytes. |
| ELISA (Enzyme-Linked Immunosorbent Assay) 1 | A highly sensitive technique used to measure the concentration of specific proteins, such as IGF-1 or inflammatory biomarkers, in blood or cerebrospinal fluid. |
Critical to evaluating any ALS treatment is the ability to measure its effects. Researchers rely on various molecular biomarkers to track disease progression and therapeutic response. The table below highlights some key biomarkers relevant to the neuroinflammatory and neurodegenerative processes in ALS that therapies aim to modify.
| Biomarker | Associated Process | Research Finding in ALS |
|---|---|---|
| IL-6 & TNF-α 1 | Inflammation | Increased levels in serum/plasma, indicating active neuroinflammation targeted by MSC therapy. |
| Neurofilament Light Chain (NFL) 1 | Neurodegeneration | Elevated serum levels correlate with neuronal damage; potential marker for treatment response. |
| Cystatin C 1 | Neurodegeneration | High plasma levels observed in ALS patients. |
| Monocyte Chemoattractant Protein-1 (MCP-1) 1 | Inflammation | Elevated plasma levels indicate inflammatory component modifiable by MSC treatment. |
Despite the promising rationale and encouraging preclinical results, significant challenges remain in translating MSC-IGF-1 therapy into a widely available treatment for ALS. Researchers must optimize delivery methods—whether intravenous, intrathecal (into the spinal fluid), or direct spinal cord transplantation—to ensure the cells reach their targets efficiently and safely 5 .
Dosing strategies, including the number of cells administered and the timing of treatments, need careful determination. The field must also address practical challenges related to cell manufacturing, quality control, and the potential need for immunosuppression, though MSCs have the advantage of being relatively immunoprivileged 5 .
The future of ALS treatment may lie in combination therapies that address the disease through multiple mechanisms simultaneously. MSC-IGF-1 therapy could potentially be combined with other approaches, such as the recently approved drug tofersen for SOD1-ALS or other investigational agents targeting different aspects of the disease.
As research continues, the prospect of using a patient's own cells (autologous transplantation) or carefully screened donor cells (allogeneic transplantation) offers hope for personalized treatment approaches that could significantly alter the ALS landscape.
The exploration of mesenchymal stem cells engineered to produce IGF-1 represents more than just another experimental treatment—it embodies a fundamental shift in how we approach complex neurodegenerative diseases. By harnessing and enhancing the body's own repair mechanisms, this strategy acknowledges and addresses the multifaceted nature of ALS.
While challenges remain, the scientific community continues to refine this approach, buoyed by encouraging preclinical results and growing understanding of ALS mechanisms. For patients and families facing an ALS diagnosis, this research represents a tangible hope—that the progressive nature of this devastating disease may one day be met with a treatment capable of altering its course.
The path from laboratory discovery to widely available treatment is long and complex, but each step forward in understanding how to protect motor neurons brings us closer to a future where ALS is no longer a terminal diagnosis, but a manageable condition.