Alzheimer's Disease Calcium Channel and Homeostasis Therapy Companies

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Alzheimer's Disease Calcium Channel and Homeostasis Therapy Companies

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Overview

flowchart TD companies_ad_calcium_channel_h["Alzheimers Disease Calcium Channel and Homeosta"] style companies_ad_calcium_channel_h fill:#4fc3f7,stroke:#333,color:#000 companies_ad_calcium_0["Scientific Rationale"] companies_ad_calcium_channel_h -->|"includes"| companies_ad_calcium_0 style companies_ad_calcium_0 fill:#81c784,stroke:#333,color:#000 companies_ad_calcium_1["Calcium Dysregulation in AD"] companies_ad_calcium_channel_h -->|"includes"| companies_ad_calcium_1 style companies_ad_calcium_1 fill:#ef5350,stroke:#333,color:#000 companies_ad_calcium_2["Therapeutic Approaches"] companies_ad_calcium_channel_h -->|"includes"| companies_ad_calcium_2 style companies_ad_calcium_2 fill:#ffd54f,stroke:#333,color:#000 companies_ad_calcium_3["Calcium-Sensing Receptor CaSR"] companies_ad_calcium_channel_h -->|"includes"| companies_ad_calcium_3 style companies_ad_calcium_3 fill:#ce93d8,stroke:#333,color:#000 companies_ad_calcium_4["Store-Operated Calcium Entry SOCE"] companies_ad_calcium_channel_h -->|"includes"| companies_ad_calcium_4 style companies_ad_calcium_4 fill:#4fc3f7,stroke:#333,color:#000 companies_ad_calcium_5["Key Companies"] companies_ad_calcium_channel_h -->|"includes"| companies_ad_calcium_5 style companies_ad_calcium_5 fill:#81c784,stroke:#333,color:#000

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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 activation

Clinical 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/)

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📊 Evidence Profile Foundational

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📗 Cite This Artifact

Alzheimer's Disease Calcium Channel and Homeostasis Therapy Companies

Overview

Overview

Scientific Rationale

Calcium Dysregulation in AD

Therapeutic Approaches

Calcium-Sensing Receptor (CaSR)

Store-Operated Calcium Entry (SOCE)

Key Companies

L-Type Calcium Channel Modulators

Avanashi Brands

MeditiC Pharma

Daiichi Sankyo Co., Ltd.

Eli Lilly and Company

AbbVie Inc.

T-Type Calcium Channel Modulators

Accerise Inc.

Potassium-Activated Calcium Channels (CaSR)

Anavex Life Sciences Corp.

SOCE and Calcium Entry Modulators

Cerevel Therapeutics

Kv7 Potassium and Calcium Modulation

Biohaven Pharmaceutical Holding Company Ltd.

Pfizer Inc.

Competitive Landscape

Therapeutic Potential in AD

Disease-Modifying Mechanisms

Clinical Development Considerations

Cross-References

External Links

References

💬 Discussion