What can be rescued?
Can normal TTC19 expression restore disease-relevant Complex III and cellular phenotypes?
Research Programme
Build the evidence.
Test the right ideas.
The scientific centre of the initiative: projects, mechanisms, therapeutic questions, experimental priorities and collaboration.
RESEARCH PRINCIPLEEvidence → Models → Experiments → Translation
Active projects
What we are working on now.
Projects are labelled by stage so analysis, hypothesis and planned experimental work are not confused.
Project
Workstream
Stage
Status
TTC19 Evidence Atlas
Structured, searchable literature and research-gap map.
Evidence
Curation and synthesis
Active
Published phenotype matrix
Compare progression, imaging, genotype and reported features across cases.
Natural history
Data extraction
Active
Computational drug repurposing
Network proximity and GraphSAGE link prediction on a shared drug–gene and protein interaction graph.
Discovery
Initial analysis complete; further work planned
Ongoing
Disease-model landscape
Identify existing cell and animal models and the highest-value model gaps.
Mechanism
Scoping
Planned
Phenotype & natural history
Progression matters as much as presence or absence.
Motor & gaitAtaxia, balance loss, dystonia, weakness and loss of independent ambulation have been reported.
Speech & orofacial functionDysarthria, speech impairment and orofacial apraxia may be prominent and measurable longitudinally.
CognitionCognitive regression occurs in the reported spectrum, with variable age of onset and progression.
NeuroimagingStriatal, brainstem, cerebellar and Leigh-like patterns recur in the literature.
Peripheral featuresPeripheral neuropathy and other systemic features occur in some reports.
Measuring change over timeA key priority is to identify reliable measures of speech, movement, cognition and daily function that can track TTC19 progression and help future studies judge whether an intervention is making a meaningful difference.
Disease mechanism
A defined gene gives us a tractable starting point.
TTC19 variantsBiallelic pathogenic change
→
TTC19 dysfunctionReduced and abnormal protein function
→
Complex III defectQuality-control and respiratory impairment
→
Cellular stressEnergy and downstream consequences
What is measurable?
Which biochemical, respiratory and cellular readouts are robust enough for candidate testing?
What is modifiable?
Which downstream pathways are causal contributors rather than secondary markers?
Therapeutic landscape
Multiple routes. Different evidence thresholds.
Drug repurposing
Computational prioritisation followed by disease-relevant experimental validation.
Mitochondrial modulation
Test whether downstream mitochondrial stress or compensatory pathways can be modified meaningfully.
Gene replacement
Determine whether functional TTC19 can rescue measurable phenotypes and what delivery constraints matter.
RNA approaches
Assess whether RNA-based restoration is biologically feasible and deliverable to relevant tissues.
Readthrough and editing
Some molecular strategies may depend on the exact pathogenic variant and require variant-specific feasibility.
Natural-history readiness
Future trials require measurable outcomes, progression data and a research-ready patient community.
No approach shown here is presented as a proven treatment for TTC19. These are research routes whose value depends on experimental evidence.
How we work
Modern tools, careful interpretation.
We use modern computational, data-driven and AI-assisted tools where they can help organise evidence, identify research priorities and generate testable hypotheses. These methods can make a small research programme more efficient, but they do not replace scientific validation.
Computational outputs are treated as starting points for further investigation. Claims about mechanisms or potential treatments require appropriate experimental evidence before they can be taken further.
Research roadmap
Move from organisation to experimentation.
PHASE 1 • NOW
Organise
Evidence Atlas, phenotype data, computational outputs and research questions.
PHASE 2
Model
Locate or develop relevant TTC19-deficient systems and reproducible assays.
PHASE 3
Test
Functional rescue and prioritised candidate experiments with predefined criteria.
PHASE 4
Translate
Use credible preclinical results to support larger funding and specialist development.
For researchers
Could your expertise solve one part of the TTC19 problem?
Useful collaborations may involve a model, assay, technology, dataset or one well-designed experiment.
Start a research conversationPriority expertise
- Patient-derived cellular models
- TTC19 functional rescue
- Complex III assembly and activity assays
- Mitochondrial respiration phenotyping
- Drug and compound screening
- Natural-history analysis
- Gene and RNA delivery
- Computational therapeutic prioritisation
Evidence first