Introduction to CNS Drug Discovery
Central nervous system (CNS) disorders remain one of the largest global unmet medical needs, though recent breakthroughs show that the field long dubbed “the graveyard of drug development” is finally booming. AI-enabled target discovery, blood-brain-barrier (BBB) shuttle chemistry, gene-editing payloads and adaptive platform trials are converging to accelerate CNS drug discovery and CNS drug development across Alzheimer’s disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD) and several genetically-defined dementias. For investors or partners searching for agile CNS pharmaceutical companies, the pipeline tour below highlights where the science—and market opportunity—is hottest.
State-of-the-Art CNS Drug Discovery
- Structure + AI guided chemistry: Shrinks lead-optimization timelines and predicts BBB-permeable conformations.
- Receptor mediated BBB shuttles: Converts larger molecule and biologics (E.g. mAbs and PROTACs) into brain-penetrant therapies.
- Gene & RNA editing modalities: Allele-selective silencing of toxic proteins, single-dose cures.
- Adaptive & platform trails: Re-use placebo arms, test multiple assets in parallel.
Alzheimer’s Disease Drug Development
Disease snapshot: Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β plaques, tau tangles leading to widespread synaptic loss. AD affects ~55 million people worldwide and is the primary target for Alzheimer’s discovery programs because disease burden and market size are unmatched.
| Mechanism | Asset | 2023-25 milestone |
|---|---|---|
| Anti-Aβ protofibril | Lecanemab | 27 % cognitive-decline slowing in 18-mo CLARITY-AD phase-3 trial (van Dyck 2023) |
| Anti-Aβ plaque | Donanemab | Positive TRAILBLAZER-ALZ-2 data; EMA review underway (Sims 2023) |
More than 140 Alzheimer’s drugs in development now tackle tau, microglia immunity and metabolic pathways, reflecting a robust Alzheimer’s drug discovery ecosystem that ranges from big pharma to nimble startups. One major challenge that remains is the early discovery of AD.
Multiple Sclerosis Drug Development
Disease snapshot: Multiple Sclerosis (MS) is a chronic, immune-mediated demyelinating disease of the brain and spinal cord. Relapses and progressive neuro-degeneration lead to cumulative disability, making brain-penetrant immunomodulators and remyelination agents prime targets for CNS drug development.
| Mechanism | Asset | 2024-25 milestone |
|---|---|---|
| Bruton’s tyrosine kinase (BTK) inhibitor | Evobrutinib | Phase-3 data confirmed serum NfL lowering and MRI lesion reduction (Montalban 2024) |
| BTK inhibitor | Tolebrutinib | GEMINI / HERCULES programs slowed disability in non-relapsing SPMS (Oh 2025) |
Second-generation BTK inhibitors dominates today’s CNS drug pipeline against MS, while remyelination agents (Clemastine, Opicinumab) and antigen-specific tolerizing vaccines line up as combination partners.
Amyotrophic Lateral Sclerosis Drug Development
Disease snapshot: Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive motor-neuron disease that leads to respiratory failure within 3–5 years. Only riluzole and edaravone are approved, so precision-genetic and immune-modulatory strategies represent urgent ALS treatments in development.
| Mechanism | Asset | 2024-25 milestone |
|---|---|---|
| SOD1-targeted antisense oligonucleotide | Tofersen | Open-label extension confirms neurofilament-light reduction & functional preservation (Wiesenfarth 2024) |
| Immune modulation | Low-dose IL-2 | Phase-3 trial shows survival benefit in biomarker-defined subgroup (Bensimon 2025) |
More than a dozen genotype-directed ASOs (FUS, C9orf72) are recruiting, backed by data-sharing alliances among CNS pharmaceutical companies.
Parkinson’s Disease Drug Development
Disease snapshot: Parkinson’s Disease (PD) stems from progressive loss of dopaminergic neurons in the substantia nigra with α-synuclein aggregation. Current therapies replace dopamine but do not alter disease course, driving focus on disease-modifying approaches for this major CNS drug pipeline indication.
| Mechanism | Asset | 2024-25 milestone |
|---|---|---|
| Type-II LRRK2 kinase inhibitors | RN222 | First selective series show neuroprotection (Raig 2024) |
| hESC-derived cell therapy | Bemdaneprocel | Phase I trials reports graft survival & dopaminergic innervation (Tabar 2025) |
| Anti-α-syn mAb | Prasinezumab | PASADENA extension slows motor progression (Pagano 2024) |
Gene-therapy vectors (AADC, GBA correction) and orally bioavailable GLP-1 analogues are also advancing through early trials.
Huntington’s Disease Drug Development
Disease snapshot: Huntington’s Disease (HD) is an autosomal-dominant CAG-repeat expansion in HTT causing inexorable motor, cognitive and psychiatric decline—an ideal test-bed for one-shot gene-silencing strategies.
| Mechanism | Asset | 2024-25 milestone |
|---|---|---|
| HTT-lowering antisense oligonucleotides | Tominersen | GENERATION-HD2 (refined dosing) enrolling after CSF mHTT suppression & improved safety (McColgan 2023) |
| Intrathecal AAV-miRNA | AMT-130 | FDA Breakthrough Therapy Designation |
| Allele-selective siRNA | WVE-003 | Positive results in Phase 1b/2a SELECT-HD clinical trial |
Frontotemporal Dementia Drug Development
Disease snapshot: Frontotemporal Dementia (FTD) is the most common young-onset dementia after AD; ≈35 % of cases arise from single-gene mutations (GRN, MAPT, C9orf72), enabling biomarker-driven trials.
| Mechanism | Asset | 2024-25 milestone |
|---|---|---|
| AAV9-GRN gene therapy | PR006/PBFT02 | CSF progranulin normalization & lysosomal rescue (Sevigny 2024) |
| Anti-sortilin mAb | Latozinemab | Pivotal INFRONT-3 phase 3 fully enrolled; OLE shows ≥50 % PGRN rise & slowed atrophy |
| Tau-ASO | ION363 | Phase-I dose-escalation reduced CSF tau 35 %; randomized expansion starts Q4-25 |
Dementia with Lewy Bodies Drug Development
Disease snapshot: Dementia with Lewy Bodies (DLB)—the second-most-common neurodegenerative dementia—features early cognitive fluctuations, visual hallucinations and α-synuclein pathology yet lacks disease-modifying therapies.
| Mechanism | Asset | 2024-25 milestone |
|---|---|---|
| σ-2 receptor modulator | CT1812 | Phase-2 SHIMMER (n = 130) met primary safety & improved attentional fluctuations |
| Anti-α-syn mAb | Cinpanemab | Next-gen mAb enters adaptive Phase-IIa with RT-QuIC CSF enrichment |
| BBB-penetrant GLP-1R/GIP agonist | ATH-1020 | IND-enabling tox complete; preclinical α-syn clearance |
Conclusion
From amyloid-clearing antibodies in AD to gene-silencing vectors in HD and progranulin restoration in FTD, mechanism-based strategies are delivering clinically meaningful signals across the neuro-degenerative spectrum. For stakeholders scouting Alzheimer’s pharmaceutical companies or broader CNS pharmaceutical companies, key differentiators now include:
- Genetic & biomarker alignment — trials enrich for patients most likely to respond.
- Innovative delivery — BBB shuttles, intrathecal AAVs and in vivo cell grafts.
- Platform optionality — assets readily redeployed across AD, PD, ALS, HD, FTD and DLB.
The integrated pipeline above shows how CNS drug discovery has moved from promise to patient impact—an inflection point ripe for partnership and investment.
If you want to start your Drug Discovery Campaign, take a look at Vipergen’s services
References
- Bensimon, G. et. al. Efficacy and safety of low-dose IL-2 as an add-on therapy to riluzole (MIROCALS): a phase 2b, double-blind, randomised, placebo-controlled trial. Lancet, 2025, 405, 1837-1850. doi.org/10.1016/S0140-6736(25)00262-4
- van Dyck, C. H. et. al. Lecanemab in Early Alzheimer’s Disease, N. Engl. J. Med., 2023, 388, 9-21. doi.org/10.1056/NEJMoa2212948
- McColgan, P. et. al. Tominersen in Adults with Manifest Huntington’s Disease. N. Engl. J. Med. 2023, 389, 2203-2205. doi.org/10.1056/NEJMc2300400
- Montalban, X. et. al. Safety and efficacy of evobrutinib in relapsing multiple sclerosis (evolutionRMS1 and evolutionRMS2): two multicentre, randomised, double-blind, active-controlled, phase 3 trials. Lancet Neurol., 2024, 23 (11), 1119-1132. doi.org/10.1016/S1474-4422(24)00328-4
- Oh, J. et. al. Tolebrutinib versus Teriflunomide in Relapsing Multiple Sclerosis, N. Engl. J. Med., 2025, 392, 1893-1904. doi.org/10.1056/NEJMoa2415985
- Pagano, G. et. al. Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson’s disease. Nat. Med., 2024, 30, 1096-1103. doi.org/10.1038/s41591-024-02886-y
- Raig, N. D. et. al. Type II kinase inhibitors that target Parkinson’s
disease–associated LRRK2. Sci. Adv. 2025, 11 (23), eadt2050. doi.org/10.1126/sciadv.adt2050 - Sevigny, J. et. al. Progranulin AAV gene therapy for frontotemporal dementia: translational studies and phase 1/2 trial interim results. Nat. Med. 30, 1406-1415. doi.org/10.1038/s41591-024-02973-0
- Sims, J. R. et. al. Donanemab in Early Symptomatic Alzheimer Disease The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA, 2023, 330 (6), 512-527. doi.org/10.1001/jama.2023.13239
- Tabar, V. et. al. Phase I trial of hES cell-derived dopaminergic neurons for Parkinson’s disease. Nature, 2025, 641, 978-983. doi.org/10.1038/s41586-025-08845-y
- Weisenfarth, M. et. al. Effects of tofersen treatment in patients with SOD1-ALS in a “real-world” setting – a 12-month multicenter cohort study from the German early access program. eClinicalMedicine, 2024, 69, 102495. doi.org/10.1016/j.eclinm.2024.102495