This category page covers biotechnology and pharmaceutical companies developing soluble guanylate cyclase (sGC) modulators — including sGC stimulators and sGC activators — for Alzheimer's disease and related neurodegenerative disorders. The NO-sGC-cGMP pathway represents a promising therapeutic target addressing cerebral blood flow dysfunction, oxidative stress, neuroinflammation, and protein aggregation that characterize AD pathogenesis. [1]
sGC modulators work through the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) signaling axis:
| Pathological Target | sGC Modulator Effect | Relevance to AD |
|---|---|---|
| Cerebral hypoperfusion | Vasodilation, improved CBF | [4] |
| Oxidative stress | Antioxidant, Nrf2 activation | [5] |
| Neuroinflammation | NF-κB inhibition, microglial modulation | [6] |
| Amyloid pathology | Modulation of APP processing | [7] |
| Tau pathology | Kinase/phosphatase modulation | [8] |
| Endothelial dysfunction | Improved neurovascular unit function | [9] |
Bayer AG is a German pharmaceutical company that developed riociguat (Adempas), the first FDA-approved sGC stimulator.
Approved Indication: Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) — FDA approved 2013 [10]
Alzheimer's Disease Program:
Merck KGaA (known as Merck outside the US) and Merck & Co. (US) have explored sGC activators for cardiovascular indications.
Cardiovascular Programs: Cinaciguat (BAY 58-2667) — sGC activator for acute heart failure
Alzheimer's Disease Potential:
Pfizer collaborated with Merck & Co. to develop vericiguat (Verquvo), an FDA-approved sGC stimulator for heart failure (2021) [11]
Heart Failure Program: Vericiguat — FDA approved 2021 for chronic heart failure
Alzheimer's Disease Potential:
AbbVie has interest in nitric oxide signaling modulators for neurodegenerative diseases.
Related Programs:
Alzheimer's Disease Potential:
Roche and Genentech have explored cGMP-modulating strategies.
Related Programs:
Alzheimer's Disease Potential:
| Institution | Focus Area | Key Research |
|---|---|---|
| University of Edinburgh | sGC and cerebral blood flow | [4:1] |
| University of Tubingen | sGC in neurodegeneration | [2:1] |
| Johns Hopkins | cGMP and tau pathology | [8:1] |
| University of Michigan | sGC and neuroinflammation | [6:1] |
| King's College London | NO-sGC-cGMP in AD models | [7:1] |
As of 2026, no sGC modulators have reached late-stage clinical trials for Alzheimer's disease. Early-stage programs include:
Challenges:
Opportunities:
| Company | Compound | Mechanism | Stage | Indication |
|---|---|---|---|---|
| Bayer | Riociguat | sGC stimulator | Preclinical | AD |
| Merck KGaA | Cinaciguat | sGC activator | Preclinical | AD |
| Pfizer/Merck & Co. | Vericiguat | sGC stimulator | Preclinical | AD |
| AbbVie | Various | NOS/sGC modulators | Discovery | AD |
| Roche/Genentech | Various | cGMP modulation | Discovery | AD |
Evgenov et al. Nat Rev Drug Discov (2006) — sGC stimulators: a novel therapeutic approach. 2006. ↩︎
Stasch et al. Pharmacol Ther (2011) — sGC stimulators and activators. 2011. ↩︎ ↩︎
Hobbs & Hunter, Nat Rev Drug Discov (2020) — sGC modulators clinical development. 2020. ↩︎
Liu et al. J Cereb Blood Flow Metab (2014) — sGC and cerebral blood flow. 2014. ↩︎ ↩︎
Zhang et al. J Neurosci (2020) — sGC activation and neuroprotection. 2020. ↩︎
Nagai et al. J Neurochem (2019) — sGC and neuroinflammation. 2019. ↩︎ ↩︎
Sullivan et al. Mov Disord (2022) — sGC in PD models. 2022. ↩︎ ↩︎
Thal et al. Brain (2018) — cGMP and tau pathology. 2018. ↩︎ ↩︎
Lang et al. J Clin Invest (2021) — Cerebrovascular dysfunction in neurodegeneration. 2021. ↩︎
Ghofrani et al. N Engl J Med (2013) — Riociguat for CTEPH. 2013. ↩︎
Armstrong et al. N Engl J Med (2020) — Vericiguat in heart failure. 2020. ↩︎