Digital Twin
EXPLORATORYPhase 10.3 — Multi-scale computational model of the SMA motor neuron. Simulates drug combinations across 5 compartments (soma, axon, NMJ, dendrites, nucleus) and 8 signaling pathways. Predicts synergistic drug combinations in silico.
What is a Digital Twin? A digital twin is a computational replica of a biological system — here, a single SMA-affected alpha motor neuron. Each compartment has its own health baseline, volume, and disease-specific defects derived from SMA omics data. Drug combinations are simulated by applying known mechanisms of action to relevant compartments and scoring the resulting functional recovery.
SMA Type IIIAmbulatoryRisdiplam Active9yr Wearable Data
Genotype
SMN1 del | SMN2: 4 copies
Age / Onset
46yr | Onset 13
HFMSE / RULM
50/66 | 37/37
Treatment
Nusinersen 25x > Risdiplam
356m
6MWT -23.6%
99.1kg
Weight +12kg
4,526
Steps/Day
5.57L
FVC Stable
37/37
RULM
~11x
CK 3.4x ULN
6-Minute Walk Test
Weight Trajectory
Daily Steps (monthly avg)
CK Creatine Kinase
Walking Speed Paradox: Speed UP while Distance DOWN
Gait Analysis — Same metrics used by Capogrosso Lab (Columbia) for spinal stimulation outcome measurement. 9 years of continuous wearable data = unprecedented longitudinal gait monitoring in SMA III.
Step Length (cm)
Double Support % (stability)
Gait Asymmetry %
Lung Function (FVC/FEV1) 8yr
Strength Training Progression
Weight vs 6MWT (r = -0.93)
Treatment Phases Comparison
Correlation Analysis — What Drives 6MWT Performance?
| Factor | Correlation | Strength | Interpretation |
|---|---|---|---|
| Body Weight | r = -0.93 | VERY STRONG | 1kg more = ~6m less 6MWT. Dominant factor. |
| Daily Steps | r = +0.72 | STRONG | More daily activity = better endurance test. |
| Strength Training | r = +0.68 | MODERATE | Training periods correlate with better 6MWT + lower weight. |
| Medication | confounded | UNCLEAR | Medication provides baseline stability. Weight/training effects are ON TOP of medication. Without treatment, decline would likely be much faster. Risdiplam too early to judge (5 months). |
| Lung Function | no correlation | STABLE | FVC 98% predicted. Not a limiting factor. Decline is muscular. |
Key Findings from 9 Years of Data
Training works. 13 months of strength training (2021-2022): -5.2% body fat, +1.4kg lean mass, best 6MWT (466m). Muscle building IS possible in SMA III.
Weight is the strongest predictor. 80.7kg = best walking performance. 99.1kg = worst. Every kg matters for an SMA patient.
Lung function is preserved. FVC 5.57L (98% predicted) after 8 years — the 6MWT decline is muscular, not respiratory.
Walking speed paradox. Speed INCREASED (3.3 → 4.1 km/h) while distance DECREASED. Endurance declines faster than peak performance — classic SMA fatigability pattern.
Acute events accelerate decline. Paraspinal episode (Oct 2024) dropped 6MWT by 63m. Recovery incomplete — new baseline lower than before.
Upper limbs preserved. RULM 37/37 (full score). Bench press stable at 12.5-13.5kg. SMA III proximal leg weakness with intact upper extremity function.
Testable Prediction (Live Tracking)
Prediction: If body weight drops from 99kg to 85kg through consistent training (2x/week) while maintaining Risdiplam therapy, the 6MWT is expected to improve from 356m to approximately 420-440m within 6-12 months.
Basis: Linear regression on weight vs 6MWT data (r=-0.93, n=11 paired measurements). Each 1kg reduction = ~6.1m improvement in 6MWT distance.
Tracking: This prediction will be validated with each quarterly 6MWT. Next test expected ~June 2026.
Falsification criteria: Weight at 85kg + 6MWT below 380m = medication effect is larger than estimated. Weight at 85kg + 6MWT above 420m = weight management is the strongest modifiable factor on top of medication.
Strength training program by Sven Knipphals — Der Chiro, Leipzig · Chiropraktik · Training · Gesundheit
Volbedingstr. 2, 04357 Leipzig
Patient SMA-III-001 | Anonymized | 3.7M health records | 9yr Apple Health + clinical data