# Topiramate as a Disease Altering Therapy for CSPN

> **NIH NIH U01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2020 · $874,009

## Abstract

Cryptogenic sensory peripheral neuropathy (CSPN) affects 5-10% of those over 40 years old, resulting in
reduced quality of life due to pain, sensory loss, imbalance, and fall related injuries. CSPN is a significant
cause of patient morbidity, for which there exists no disease altering therapy. Clinically similar to early diabetic
neuropathy, it is characterized by preferential injury to small axons, and frequently results in prominent sensory
loss and neuropathic pain. Injury to small axons is reflected in reduced intraepidermal nerve fiber density
(IENFD). While the precise etiology of CSPN is unknown, and likely multifactorial, accumulating evidence
indicates that obesity, dyslipidemia, and insulin resistance/prediabetes (metabolic syndrome) are linked to
CSPN risk. Patients with CSPN have an elevated risk of metabolic syndrome and patients with prediabetes
have an elevated risk of CSPN. Obesity and dyslipidemia also significantly increase the risk of neuropathy
among diabetic patients. Animal models support the hypothesis that obesity and prediabetic levels of glucose
dysregulation cause neuropathy. A growing literature suggests that exercise improves nerve regenerative
capacity, results in increased IENFD and improves neuropathic pain among patients with CSPN and
prediabetes. Cumulatively, these data support the hypothesis that metabolic syndrome is linked to neuropathy
risk, CSPN is potentially reversible, and aggressive metabolic management may be an effective strategy to
enhance nerve regeneration and improve patient symptoms. However, currently available lifestyle interventions
are very difficult to employ in a clinical setting due to poor compliance and attrition from the necessary
behavioral changes. Development of better pharmacologic approaches is a major priority. Recent data suggest
that gain of function in voltage gated sodium channels plays a role in CSPN and other common forms of
neuropathy. Topiramate is a promising therapeutic approach to CSPN. Clinical trials of this anticonvulsant
agent in diabetic neuropathy suggest improvement in pain and quality of life, and also in measures of
peripheral nerve function including sensory testing and IENFD. Topiramate has multiple potentially
neuroprotective effects. It induces significant weight loss at the dose proposed in this study, and also improves
insulin resistance. These effects are greatest among obese patients. Topiramate also blocks voltage gated
sodium channels. It has been extensively studied for the treatment of epilepsy and migraine and is generally
safe and well tolerated. Several studies suggest a potential benefit for neuropathic pain associated with
diabetic neuropathy. Small studies suggest topiramate therapy not only results in improved pain, but also
improves QOL and preferentially impacts measures of small fiber function, including an increase in IENFD.
Data from animal models of diabetes also support its potential therapeutic efficacy. While topiramate has
multiple ...

## Key facts

- **NIH application ID:** 9952436
- **Project number:** 5U01NS095388-04
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** CHRISTOPHER S. COFFEY
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $874,009
- **Award type:** 5
- **Project period:** 2018-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952436

## Citation

> US National Institutes of Health, RePORTER application 9952436, Topiramate as a Disease Altering Therapy for CSPN (5U01NS095388-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9952436. Licensed CC0.

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