# Primary sensory neuron-targeted block of Cav3.2 for treatment of chronic neuropathic pain

> **NIH NIH R33** · MEDICAL COLLEGE OF WISCONSIN · 2021 · $360,012

## Abstract

Selective block of CaV3.2 in primary sensory neurons for treatment of chronic neuropathic pain
Summary/Abstract: Chronic pain is a devastating problem, while opioid treatment of chronic pain has
numerous risks, including misuse, overdose, and addiction, highlighting the need for new analgesic targets.
The peripheral sensory nervous system (PSNS) is a particularly accessible site for devising new treatments,
where the sensory neurons of the dorsal root ganglia (DRG) initiate nociception and have a central role in the
development and maintenance of painful neuropathy. Sensory neuronal CaV3.2 T-type calcium channels
regulate neuronal excitability and are a promising target for treatment of pain, but the development of selective
CaV3.2 inhibitors has proved elusive. Small peptides, especially those derived from the natural proteins as
functionally inhibitory peptide aptamers (iPAs), are recognized as being highly effective and selective, allowing
blockade of specific pain molecular interactomes to reduce pain with minimal off-target effects. The analgesic
iPA-sustained expression in the PSNS delivered by adeno-associated viral vectors (AAV) in the DRG is a safe
and feasible path to chronic pain treatment with minimal side effects and no abuse/addiction liability.
Molecular
signaling interactions are often mediated by regions of proteins lacking a defined tertiary structure, known as
protein intrinsically disordered regions (IDRs). Using established IDR prediction algorithms, we localized highly
disordered regions in CaV3.2, and identified a novel 17mer peptide that produces sustained CaV3.2 T-type
current inhibition and pain attenuation in a neuropathic pain rat model, demonstrating its therapeutic potential
for pain treatment. The proposed Two-Phase study is to develop evidence that candidate CaV3.2iPAs delivered
by AAV into DRG neurons have sufficient biological activity to justify further development as a novel analgesic
approach. In Phase I (R66), a combined computational and experimental strategy will be used to design
candidate CaV3.2iPAs and test their inhibition of T-type current by in vitro of cell-based studies. The milestone
for advancement from R66 Phase to Phase II (R33) is identification of the top CaV3.2iPA leads that meet our
selection criteria (higher potency and selectivity in block of CaV3.2) and of production of therapeutic AAV-
CaV3.2iPAs. Phase II aims to apply AAV-CaV3.2iPAs in vivo by intraganglionic injection to evaluate critical
features of AAV-CaV3.2iPAs in nerve injury-induced rat pain model, compared to controls The milestone for the
end of Phase II is generation of sufficient data of in vivo efficacy and safety which will help us to make a go/no-
go informed decision for further translational development. Our ultimate goal is to develop a novel therapeutics
combined AAV-targeted gene delivery with potent and selective iPA block of CaV3.2 in anatomically segmental
DRG to treat chronic neuropathic pain.

## Key facts

- **NIH application ID:** 10438951
- **Project number:** 4R33NS116203-02
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Quinn H Hogan
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $360,012
- **Award type:** 4N
- **Project period:** 2021-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438951

## Citation

> US National Institutes of Health, RePORTER application 10438951, Primary sensory neuron-targeted block of Cav3.2 for treatment of chronic neuropathic pain (4R33NS116203-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10438951. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*