.png)
From Your Blood Cells to Disease Models: How iPSC Technology Is Transforming Rare Disease Research
- 22 hours ago
- 6 min read
Updated: 5 hours ago
A brief history: From discovery to Nobel Prize
In 2006, Japanese scientist Shinya Yamanaka made a breakthrough that would transform biomedical research. Working at Kyoto University with his student Kazutoshi Takahashi, Yamanaka showed that adult mouse cells could be reprogrammed back into an embryonic-like state by introducing just four genes—now called the "Yamanaka factors."
One year later, in 2007, human cells were successfully reprogrammed using the same approach. For this discovery, Yamanaka shared the 2012 Nobel Prize in Physiology or Medicine with John B. Gurdon, whose pioneering work on cell nuclear transplantation in frogs had laid the theoretical groundwork decades earlier.
Why was this so revolutionary? Because for years, biologists believed that once a cell became specialized (like a skin cell or nerve cell), it could never return to an immature state. Yamanaka proved them wrong.
What are iPSCs?
An induced pluripotent stem cell (iPSC) is a cell that has been reprogrammed to behave like an embryonic stem cell.
Here's the essence: By introducing four transcription factors (Oct4, Sox2, Klf4, and c-Myc), researchers can "reset" a mature cell back to its original state—a state where it can potentially become any cell type in the body.
The process takes 3-6 months and involves:
Taking a blood sample from a patient
Introducing the four reprogramming factors
Culturing the resulting iPSCs in the laboratory
Guiding them to become specific cell types (neurons, heart cells, etc.)
Studying what goes wrong in disease
Why it matters for disease research
For decades, studying rare genetic diseases relied on two imperfect approaches:
Animal models — Fast to work with, but animals don't always behave like humans. Metabolically, physiologically, genetically, there are significant differences. Mouse hearts beat at 400-800 times per minute; human hearts beat 60-100 times per minute. These aren't trivial differences—they affect how cells respond to drugs and disease.
Human tissue samples — Directly relevant but extremely difficult to obtain and keep alive.
iPSCs solved this problem: Researchers can now create a "disease in a dish"—patient cells reprogrammed into the exact cell types affected by the disease, in unlimited quantities.
Current clinical reality
iPSC-based therapies are no longer theoretical:
✅ Clinical trials underway: As of December 2024, over 115 clinical trials are in progress worldwide using pluripotent stem cell-based treatments (both iPSC and ESC-derived) for conditions including Parkinson's disease, vision loss, and immunological disorders.
✅ FDA support: It appears that the FDA explicitly encourages iPSC-based drug development as an alternative to animal testing.
✅ Early successes: In one case, corneal cells derived from iPSCs were transplanted into a patient with corneal disease. The patient regained vision with no adverse effects.
The drug development problem
About 90% of drugs that enter human clinical trials ultimately fail. This statistic gets misused frequently. Here's what it actually means:
Only ~10% of drugs entering Phase I human trials are eventually approved
This doesn't primarily reflect animal testing failure
Rather, it reveals the complexity of human disease and the difficulty of translating any preclinical finding (whether from animals, cells, or elsewhere) to effective human treatment
The real issue: Complex diseases involve multiple genes, environmental factors, and individual variation. No preclinical model—mouse or iPSC—perfectly replicates human disease. But iPSCs come considerably closer than mice because they're human cells with the patient's exact genetic mutations.
What about LMBRD2?
For a rare genetic disease like LMBRD2, iPSC research offers concrete advantages:
🔵 The gene is still being understood. The association between LMBRD2 variants and neurodevelopmental disorders was identified in 2021. Researchers are still determining its normal function.
🔵 Patient cells matter. With so few people affected, studying iPSC-derived neurons from LMBRD2 patients directly—observing what cellular defects occur—is far more practical than hoping to breed suitable animal models.
🔵 Mechanism first, treatment second. Before any therapy (whether ASO, gene therapy, or other) can be designed, researchers need to understand exactly what goes wrong at the cellular level. iPSCs provide that window.
The honest limitations
iPSC research is powerful but not a magic solution:
❌ Still developmental: Many iPSC therapies are in early-stage trials. Safety questions remain.
❌ Cost and time: Creating and characterizing patient-specific iPSC lines is expensive and time-consuming (6-12 months per line).
❌ Technical challenges: iPSCs can acquire chromosomal abnormalities during reprogramming. Quality control is essential.
❌ No guarantee of translation: A disease mechanism identified in iPSC models must still be validated and developed into an actual treatment—a process that can take years.
What happens next
The research pipeline for rare diseases now typically looks like this:
Understand the disease mechanism (iPSCs provide the tool)
Identify potential drug targets (what could be blocked or modified?)
Screen candidate therapies (which molecules show promise?)
Validate in additional models (test in more complex systems)
Human clinical trials (the final step)
Each step is necessary. There's no shortcut.
Frequently Asked Questions
Q: Will iPSC research cure my child?
A: iPSC research is a critical first step toward understanding LMBRD2, but it won't produce an immediate cure. Think of it as building the foundation for a house—essential, but not the completed structure. It helps identify what's wrong at the cellular level, which then guides development of potential treatments.
Q: How much does iPSC research cost?
A: Creating and characterizing a single iPSC line typically costs $10,000-30,000. A full research program (multiple lines, disease modeling, drug screening) can cost $100,000-500,000. This is why funding through foundations and research grants is essential.
Q: Can we donate cells now even if research hasn't fully started?
A: Yes! Blood or skin samples can be collected and stored. These samples remain viable for iPSC creation later. Speak with your medical team about biobanking options.
Q: My child is very young—can blood still be drawn?
A: Yes, though smaller blood volumes can be collected from young children. Alternatively, a small skin biopsy (about the size of a pencil eraser) can be used instead. Your medical team can advise on the best approach.
Q: How long until we see results?
A: Realistic timeline: 1-2 years to create iPSC lines and differentiate them into neurons, 2-4 years to understand disease mechanisms, 4-6+ years before potential drug candidates emerge. This isn't fast, but it's faster than traditional approaches for rare diseases.
Q: What if the research doesn't find anything useful?
A: Even "negative" results are valuable—they tell us what doesn't work and guide future research directions. Every well-designed study contributes to the larger understanding of LMBRD2, even if it doesn't immediately yield a treatment.
Our LMBRD2 iPSC Project
We are currently preparing a submission to the Fondation Maladies Rares "Models 2025" research call, which specifically funds the creation of cellular and animal models for rare diseases. If funded, this project would establish the first iPSC-based disease model for LMBRD2.
What would make this project possible:
The CHU de Toulouse, with Dr. Alban Ziegler and Dr. Julie Plaisancié, would support this research by managing with us sample collection, clinical follow-up, and coordination with the research laboratory performing the iPSC work. This clinical partnership would be essential—ensuring that biological samples are properly collected, characterized, and linked to detailed clinical data about each patient.
The proposed project goals:
Create iPSC lines from LMBRD2 patients
Differentiate these iPSCs into neurons (the cell type affected in LMBRD2)
Identify what goes wrong at the cellular level
Establish a platform for future drug testing
How families can support this effort:
Share your interest in participating in LMBRD2 iPSC research
Keep detailed medical records and clinical history organized
Stay informed about the project's progress
Help spread awareness about LMBRD2 research needs
If funded, this foundation would be essential for all future therapeutic development. Without understanding the basic disease mechanism in human cells, we cannot design rational treatments.
Bottom line
iPSCs represent a genuine advance in how researchers can study human disease. They're not a shortcut to treatment, but they are a powerful tool for understanding disease mechanisms—and understanding comes first.
Yamanaka's 2006 discovery showed that cellular specialization isn't permanent. Today, that insight is enabling researchers worldwide to study diseases that were previously untouchable.
For LMBRD2 and other rare genetic diseases, iPSC technology offers a practical path forward: patient cells, human biology, answers that animal models can't provide.
Want to learn more? Follow our progress as we work toward submitting this research proposal and building the scientific foundation that LMBRD2 families desperately need.
The understanding of rare diseases advances through research participation. Every family that contributes data or samples helps build the scientific knowledge that will one day lead to treatments.
For more information about participating in LMBRD2 research or to connect with our patient community, please contact us : contact@lmbrd2.org