Cure Requirements Index — Neurodegenerative Diseases

Cure Requirements Index

Overview

For each neurodegenerative disease, this index tracks: what we know, what we don't know, what experiments are needed, what technologies are needed, and estimated timeline to cure. Each requirement is scored by importance (1-10) and current progress (0-100%).

Cure Requirements Index

Overview

For each neurodegenerative disease, this index tracks: what we know, what we don't know, what experiments are needed, what technologies are needed, and estimated timeline to cure. Each requirement is scored by importance (1-10) and current progress (0-100%).

Related: [Experiment Priority Index](/experiments/experiment-priority-index) | [Novel Therapy Index](/ideas/novel-therapy-index) | [Research Gaps](/gaps/rankings)

CBS/PSP (4R-Tauopathies)

Cure Roadmap: [CBS/PSP Cure Roadmap](/mechanisms/cbs-psp-cure-roadmap)

| Requirement | Importance | Progress | Status |
|-------------|-----------|----------|--------|
| Understand why 4R-tau aggregates selectively | 10 | 40% | Spatial transcriptomics underway |
| Validate anti-tau antibody efficacy in 4R-tauopathy | 10 | 30% | E2814 Phase 3, FNP-223 Phase 2 |
| Develop 4R-tau-specific PET tracer | 9 | 50% | PI-2620 showing promise |
| Blood biomarker panel for early detection | 9 | 60% | p-tau217 + NfL validated |
| Combination therapy design (anti-tau + anti-inflammatory) | 9 | 10% | No combo trials yet |
| Gene therapy for tau reduction | 8 | 20% | VY1706 IND-enabling |
| Stem cell therapy for CBS/PSP | 7 | 10% | No CBS/PSP-specific trials |
| Pre-symptomatic detection and prevention | 8 | 5% | MAPT carriers only |
| Understand CBS vs PSP phenotype determinants | 8 | 20% | Genetic + environmental factors unknown |
| Patient stratification biomarkers | 9 | 30% | tau PET patterns emerging |

Estimated timeline to first approved DMT: 2028-2030 Estimated timeline to meaningful disease modification: 2030-2033 Estimated timeline to functional cure: 2035+

Alzheimer's Disease

Cure Roadmap: [AD Cure Roadmap](/mechanisms/ad-cure-roadmap)

| Requirement | Importance | Progress | Status |
|-------------|-----------|----------|--------|
| Clarify amyloid vs tau primacy | 10 | 70% | Lecanemab/donanemab show amyloid removal ≠ cure |
| Effective tau-directed therapy | 10 | 25% | Bepranemab 33-58% tau slowing; multiple Phase 2 |
| Combination therapy (anti-amyloid + anti-tau + anti-inflammatory) | 10 | 5% | 20 combo trials active but early |
| Blood biomarker-guided treatment selection | 9 | 70% | p-tau217 high accuracy for AD vs non-AD |
| Understand why amyloid clearance doesn't stop decline | 10 | 30% | Downstream tau/inflammation may be autonomous |
| Prevention in pre-symptomatic carriers | 9 | 40% | A4 Study, DIAN-TU ongoing |
| Neuroregeneration after damage | 8 | 5% | ARPA-H FRONT program funded |
| Address co-pathologies (TDP-43, alpha-syn, vascular) | 8 | 15% | Recognized but few multi-target trials |

Estimated timeline to meaningful disease modification: 2026-2028 (anti-amyloid + anti-tau combo) Estimated timeline to functional cure: 2035+

Parkinson's Disease

Cure Roadmap: [PD Cure Roadmap](/mechanisms/pd-cure-roadmap)

| Requirement | Importance | Progress | Status |
|-------------|-----------|----------|--------|
| Alpha-synuclein aggregation therapy | 10 | 30% | Multiple Phase 2, no clear winner |
| GLP-1 disease modification | 9 | 40% | Lixisenatide Phase 2 positive; semaglutide pending |
| Stem cell DA neuron replacement | 9 | 50% | Bemdaneprocel Phase III enrolling |
| LRRK2-targeted therapy for genetic PD | 9 | 40% | Multiple kinase inhibitors in Phase 2 |
| GBA-targeted therapy | 9 | 35% | Venglustat, ambroxol in trials |
| Gene therapy (GDNF, CDNF, AADC) | 8 | 30% | Multiple Phase 1/2 |
| Pre-symptomatic detection (SAA + prodromal markers) | 9 | 60% | SAA validated for diagnosis |
| Mitochondrial rescue | 8 | 15% | CoQ10/urolithin A modest; mito transplant early |
| Gut-brain axis intervention | 7 | 20% | FMT trials, probiotics |
| Neuroprotective exercise mechanism | 7 | 40% | BDNF pathway well-characterized |

Estimated timeline to meaningful disease modification: 2027-2029 Estimated timeline to functional cure: 2033+

ALS

Cure Roadmap: [ALS Cure Roadmap](/therapeutics/als-cure-roadmap)

| Requirement | Importance | Progress | Status |
|-------------|-----------|----------|--------|
| TDP-43 aggregation therapy | 10 | 15% | Early preclinical |
| SOD1 gene silencing | 9 | 60% | Tofersen approved (genetic ALS) |
| C9orf72 repeat expansion therapy | 9 | 30% | ASOs in Phase 1/2 |
| FUS-targeted therapy | 8 | 20% | ASOs in preclinical |
| Sporadic ALS mechanism | 10 | 15% | Most ALS is non-genetic; cause unknown |
| Muscle preservation | 8 | 20% | Exercise + nutritional support |
| Respiratory support innovation | 7 | 50% | Diaphragm pacing, improved NIV |
| Biomarkers for trial enrichment | 9 | 40% | NfL, p-NfH validated; subtyping early |

Estimated timeline to genetic ALS modification: 2026-2028 (tofersen-class) Estimated timeline to sporadic ALS modification: 2032+

Cross-Disease Requirements

| Requirement | Importance | Progress | Applicable Diseases |
|-------------|-----------|----------|-------------------|
| BBB-penetrant drug delivery platform | 10 | 30% | All |
| AI-driven drug target prediction | 8 | 40% | All |
| Multi-omics patient stratification | 9 | 25% | All |
| Adaptive clinical trial platforms for rare diseases | 9 | 35% | CBS/PSP/ALS/FTD |
| Computational disease modeling (digital twins) | 8 | 15% | All |
| Shared neuroinflammation modulation | 9 | 30% | All |
| Selective neuronal vulnerability mechanism | 10 | 20% | All |
| Protein quality control enhancement | 9 | 25% | All proteinopathies |

See Also

• [Experiment Priority Index](/experiments/experiment-priority-index)
• [Novel Therapy Index](/ideas/novel-therapy-index)
• [Research Gaps Rankings](/gaps/rankings)
• [Hypothesis Rankings](/hypotheses/rankings)