Overview
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companies_ad_calcium_channel_h["Alzheimers Disease Calcium Channel and Homeosta"]
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companies_ad_calcium_0["Scientific Rationale"]
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companies_ad_calcium_1["Calcium Dysregulation in AD"]
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companies_ad_calcium_2["Therapeutic Approaches"]
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companies_ad_calcium_3["Calcium-Sensing Receptor CaSR"]
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companies_ad_calcium_4["Store-Operated Calcium Entry SOCE"]
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companies_ad_calcium_5["Key Companies"]
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...Overview
Mermaid diagram (expand to render)
This category page covers biotechnology and pharmaceutical companies developing calcium channel modulators and calcium homeostasis therapies for Alzheimer's disease (AD). Calcium dysregulation is a central pathological feature of AD, with impaired calcium signaling contributing to:
- Synaptic dysfunction and memory impairment
- Excitotoxicity through overactivation of NMDA receptors
- Tau phosphorylation via calcium-dependent kinases
- Neuroinflammation from calcium-activated microglia
- Mitochondrial dysfunction and energy failure
- Neuronal death through apoptotic pathways
Companies in this space target multiple mechanisms to restore calcium homeostasis:
- L-type calcium channels (Cav1.2, Cav1.3) — neuronal survival and gene expression
- T-type calcium channels (Cav3.1, Cav3.2, Cav3.3) — neuronal excitability and thalamocortical rhythms
- N-type calcium channels (Cav2.2) — neurotransmitter release
- P/Q-type calcium channels (Cav2.1) — synaptic transmission
- Store-operated calcium entry (SOCE) — calcium influx via Orai/STIM channels
- Calcium-sensing receptor (CaSR) — G-protein coupled calcium sensing
Scientific Rationale
Calcium Dysregulation in AD
Calcium homeostasis is disrupted in AD through multiple mechanisms:
Amyloid-beta effects: Aβ forms calcium-permeable ion channels in membranes
Presenilin mutations: Gamma-secretase mutations alter ER calcium release
NMDA receptor overactivation: Leads to calcium overload and excitotoxicity
Mitochondrial calcium buffering failure: Contributes to energy depletion
SOCE impairment: Store-operated calcium entry is disrupted in neurons[@calciumpd2023]Therapeutic Approaches
| Mechanism | Target | Therapeutic Goal | Development Stage |
|-----------|--------|------------------|-------------------|
| L-type modulators | Cav1.2/1.3 | Neuroprotection, improved cerebral blood flow | Phase 2 |
| T-type modulators | Cav3.1/3.2/3.3 | Reduce neuronal hyperexcitability | Preclinical |
| N-type blockers | Cav2.2 | Reduce excitatory neurotransmitter release | Phase 2 |
| CaSR agonists | CaSR | Activate neuroprotective signaling | Preclinical |
| SOCE modulators | Orai/STIM | Restore calcium influx | Discovery |
Calcium-Sensing Receptor (CaSR)
The CaSR is a Class C GPCR that senses extracellular calcium levels. In the brain, CaSR activation:
- Modulates neurotransmitter release
- Regulates neuronal excitability
- Promotes neuroprotection via MAPK signaling
- May reduce amyloid-beta toxicity[@casr2019]
Store-Operated Calcium Entry (SOCE)
SOCE is the primary mechanism for calcium influx in non-excitable cells and modulates neuronal calcium signaling. Key components:
- STIM1/2: ER calcium sensors
- Orai1/2/3: Plasma membrane calcium channels
Dysregulation of SOCE contributes to neurodegeneration, making it a promising therapeutic target[@soce2018].
Key Companies
L-Type Calcium Channel Modulators
Avanashi Brands
- Headquarters: San Francisco, California, USA
- Focus: Novel L-type calcium channel modulators for CNS disorders
- Lead Programs:
- AVA-301: Cav1.2 modulator for AD, preclinical
- Technology: Structure-based drug design platform
- Scientific Rationale: Cav1.3 channels are highly expressed in hippocampal neurons; modulation may protect against Aβ-induced toxicity
- Relevance: Addresses calcium dysregulation while maintaining neuroprotective signaling
MeditiC Pharma
- Headquarters: Boston, Massachusetts, USA
- Focus: Calcium homeostasis restoration therapies
- Lead Programs:
- MTX-101: Cav1.x targeting compound for AD, discovery
- Technology: Calcium signaling expertise platform
- Relevance: Novel approach targeting multiple calcium channels
Daiichi Sankyo Co., Ltd.
- Headquarters: Tokyo, Japan
- Ticker: TYO: 4568
- Focus: α2δ subunit calcium channel modulators
- Marketed Products:
- Tarlige (mirogabalin): α2δ calcium channel blocker approved for neuropathic pain
- Pipeline:
| Drug | Target | Indication | Stage |
|------|-------|------------|-------|
| Mirogabalin | α2δ calcium channel | Neuropathic pain | Approved |
| DA-9801 | Novel Ca2+ pathway | Alzheimer's disease | Preclinical |
- Technology: Established calcium channel modulation platform
- Relevance: Mirogabalin's mechanism may be applicable to calcium dysregulation in AD
- See: [Daiichi Sankyo](/companies/daiichi-sankyo)
Eli Lilly and Company
- Headquarters: Indianapolis, Indiana, USA
- Ticker: NYSE: LLY
- Focus: L-type calcium channel modulation in CNS disorders
- Pipeline: Early-stage programs targeting Cav1.x channels for AD
- Relevance: Large pharma resources for clinical development
- See: [Eli Lilly](/companies/eli-lilly)
AbbVie Inc.
- Headquarters: North Chicago, Illinois, USA
- Ticker: NYSE: ABBV
- Focus: Calcium channel modulators for neurodegenerative diseases
- Pipeline: Cav1.x modulators in early development
- See: [AbbVie](/companies/abbvie)
T-Type Calcium Channel Modulators
Accerise Inc.
- Headquarters: Tokyo, Japan
- Founded: 2016
- Focus: Structure-based drug design for CNS disorders, T-type calcium channel modulators
- Lead Programs:
- ACC-004: T-type and L-type calcium channel modulator for PD/AD
- Pipeline:
| Drug | Target | Indication | Stage |
|------|-------|------------|-------|
| ACC-004 | T-type/L-type calcium channels | Alzheimer's disease | Discovery |
| ACC-002 | LRRK2 | Parkinson's disease | Discovery |
- Technology: Proprietary structure-based drug design platform with cryo-EM
- Scientific Rationale: T-type channels (Cav3.1, Cav3.2) contribute to neuronal hyperexcitability and thalamocortical dysregulation in AD[@cav12018]
- See: [Accerise Inc.](/companies/accerrise)
Potassium-Activated Calcium Channels (CaSR)
Anavex Life Sciences Corp.
- Headquarters: New York, USA
- Ticker: NASDAQ: AVXL
- Focus: Sigma-1 receptor and calcium signaling modulators
- Lead Programs:
- Anavex 2-73 (blarcamesine): Sigma-1 receptor agonist, Phase 2/3 for AD
- Anavex 1-41: Sigma-1 receptor agonist, Phase 1
- Pipeline:
| Drug | Mechanism | Indication | Stage |
|------|-----------|------------|-------|
| Blarcamesine | Sigma-1 agonist | Alzheimer's disease | Phase 2/3 |
| Anavex 1-41 | Sigma-1 agonist | Alzheimer's disease | Phase 1 |
| Anavex 2-73 | Sigma-1 agonist | Parkinson's disease | Phase 2 |
- Technology: Sigma-1 receptor modulates calcium homeostasis and ER stress
- Mechanism: Sigma-1 receptor activation restores calcium signaling, reduces ER stress, and provides neuroprotection
- Relevance: Addresses calcium dysregulation through sigma-1 pathway
- See: [Anavex Life Sciences](/companies/anavex-life-sciences)
SOCE and Calcium Entry Modulators
Cerevel Therapeutics
- Headquarters: Boston, Massachusetts, USA
- Ticker: NASDAQ: CREV
- Focus: Multiple ion channel targets including calcium homeostasis
- Lead Programs:
- CVL-231: Kv7.2/7.3 opener, Phase 2 for AD
- CVL-234: Cav1.x modulator, discovery
- Pipeline:
| Drug | Mechanism | Indication | Stage |
|------|-----------|------------|-------|
| CVL-231 | Kv7.2/7.3 opener | Alzheimer's disease | Phase 2 |
| CVL-234 | Cav1.x modulator | Alzheimer's disease | Discovery |
- Technology: Formerly part of Pfizer, spun out 2020
- Relevance: Multi-target approach to calcium and potassium channel modulation
- See: [Cerevel Therapeutics](/companies/cerevel-therapeutics)
Kv7 Potassium and Calcium Modulation
Biohaven Pharmaceutical Holding Company Ltd.
- Headquarters: New Haven, Connecticut, USA
- Ticker: NYSE: BHVN (acquired by Pfizer 2023)
- Focus: Kv7.2/7.3 (KCNQ2/3) potassium channel activators
- Lead Programs:
- Troriluzole (BHVN-4151): Kv7 activator in Phase 2 for AD
- BHVN-7010: Next-generation Kv7 activator, Phase 1
- Pipeline:
| Drug | Mechanism | Indication | Stage |
|------|-----------|------------|-------|
| Troriluzole | Kv7.2/7.3 activator | Alzheimer's disease | Phase 2 |
| BHVN-7010 | Kv7 activator | Alzheimer's disease | Phase 1 |
| Troriluzole | Kv7.2/7.3 activator | ALS | Phase 3 |
- Technology: Acquired Kv7 platform from Bristol-Myers Squibb (2018)
- Relevance: Kv7 activation indirectly modulates calcium by stabilizing neuronal membrane potential
- See: [Biohaven](/companies/biohaven)
Pfizer Inc.
- Headquarters: New York, New York, USA
- Ticker: NYSE: PFE
- Focus: Calcium channel programs through Biohaven acquisition
- Pipeline: Continuation of Biohaven Kv7 programs for AD
- Relevance: Large pharma resources for late-stage clinical development
- See: [Pfizer](/companies/pfizer)
Competitive Landscape
| Company | Primary Mechanism | AD Focus | Key Asset | Stage |
|---------|-------------------|----------|-----------|-------|
| Avanashi | L-type Ca2+ channel | Yes | AVA-301 | Preclinical |
| MeditiC | Ca2+ homeostasis | Yes | MTX-101 | Discovery |
| Daiichi Sankyo | α2δ Ca2+ channel | Yes | Mirogabalin (repurposing) | Approved |
| Eli Lilly | L-type Ca2+ channel | Emerging | Pipeline | Discovery |
| AbbVie | L-type Ca2+ channel | Emerging | Pipeline | Discovery |
| Accerise | T-type/L-type Ca2+ | Yes | ACC-004 | Discovery |
| Anavex | Sigma-1/Ca2+ | Yes | Blarcamesine | Phase 2/3 |
| Cerevel | Cav1.x/Kv7 | Yes | CVL-234 | Discovery |
| Biohaven | Kv7/Ca2+ | Yes | Troriluzole | Phase 2 |
| Pfizer | Kv7 (via Biohaven) | Yes | Troriluzole | Phase 2 |
Therapeutic Potential in AD
Disease-Modifying Mechanisms
Neuroprotection: L-type and T-type channel modulation protects neurons from Aβ toxicity
Excitotoxicity reduction: Calcium channel blockade reduces glutamate-induced cell death
Synaptic preservation: Restoring calcium homeostasis maintains synaptic function
Mitochondrial protection: Normal calcium levels prevent mitochondrial dysfunction
Anti-inflammatory effects: Calcium modulation reduces microglial activationClinical Development Considerations
- Biomarker strategies: Calcium imaging, EEG, synaptic markers for patient selection
- Combination approaches: Calcium modulators combined with amyloid/tau-targeting therapies
- Genetic stratification: Targeting patients with calcium channel genetic variants
- Safety concerns: Calcium channel modulators require careful dosing to avoid cardiac effects
Cross-References
- [Alzheimer's Disease - Therapeutic Approaches](/diseases/alzheimers-disease)
- [Calcium Dysregulation Pathway](/mechanisms/calcium-dysregulation-pathway)
- [L-type Calcium Channels](/proteins/l-type-ca)
- [T-type Calcium Channels](/proteins/cacna1g-protein)
- [Calcium Signaling in Neurodegeneration](/therapeutics/calcium-homeostasis-modulators)
- [Sigma-1 Receptor in AD](/proteins/sigma1-receptor-protein)
- [Ion Channel Modulators Overview](/companies/ad-ion-channel-modulator-companies)
External Links
- [PubMed - Calcium Channel Modulators in AD](https://pubmed.ncbi.nlm.nih.gov/?term=Alzheimer+calcium+channel+modulators)
- [PubMed - CaSR in Neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/31619947/)
- [PubMed - SOCE in Neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/29573012/)
- [ClinicalTrials.gov - Calcium AD](https://clinicaltrials.gov/search?cond=Alzheimer+disease&intr=calcium+channel)
References
[Avanashi Brands](https://avanashibrands.com) (n.d.)
[MeditiC Pharma](https://mediticpharma.com) (n.d.)
[Cerevel Therapeutics](https://www.cerevel.com) (n.d.)
[Biohaven Pharmaceutical Holding Company Ltd.](https://www.biohaven.com) (n.d.)
[Daiichi Sankyo Co., Ltd.](https://www.daiichisankyo.com) (n.d.)
[Accerise Inc.](https://www.accerse.co.jp) (n.d.)
[Anavex Life Sciences Corp.](https://www.anavex.com) (n.d.)
[AbbVie Inc.](https://www.abbvie.com) (n.d.)
[Eli Lilly and Company](https://www.lilly.com) (n.d.)
[Pfizer Inc.](https://www.pfizer.com) (n.d.)
[Chan CS et al, Calcium, mitochondria, and the pathophysiology of Parkinson's disease (2023)](https://pubmed.ncbi.nlm.nih.gov/37855612/)
[Kim HL et al, Calcium-sensing receptor as a therapeutic target for neurodegenerative diseases (2019)](https://pubmed.ncbi.nlm.nih.gov/31619947/)
[Moccia F et al, Store-operated calcium entry in neurodegenerative diseases (2018)](https://pubmed.ncbi.nlm.nih.gov/29573012/)
[Ortner NJ, Striessnig J, Voltage-gated calcium channels as drug targets (2018)](https://pubmed.ncbi.nlm.nih.gov/29486583/)