National Center for Complementary and Integrative Health (NCCIH)
Background: PIEZO2 Deficiency Syndrome (PDS) is a genetic disorder that affects a person s ability to feel touches and pain. Researchers want to know more about how PDS changes nerve function. Objective: To compare nerve function in people with PDS to that in people without PDS. Eligibility: People aged 18 years and older with PDS enrolled in protocol 16-AT-0077. Healthy volunteers are also needed. Design: Participants will have at least 1 clinic visit. They will undergo a test that measures activity in the nerves. For the test: Participants will place their arm or leg in a comfortable position. Ultrasound will be used to locate nerves. A smooth wand will be slid over the skin to capture images of the structures below. Two thin needles will be inserted through the skin. These needles are much smaller than the kind used to draw blood. The needles will record nerve activity as different sensations are applied to the skin. These include mild electrical pulses; heat and cold; bending of the knee or elbow; vibration; air puffs; pulling a hair; and tapping, stroking (brushing), stretching, pinching, and pushing on the skin at different levels of force. Each test takes 5 to 10 minutes. Participants will describe the sensations they feel. Participants may opt for an additional test that measures how nerves respond after heat pulses are used to create mild redness on the skin. Researchers would like at least 2 tests from each person. Participants may return for up to 3 additional visits, if desired, to complete all the testing.
PIEZO2-Deficiency Syndrome
Study Description: The study aims to characterize peripheral nerve function and physiology in healthy participants and participants with inherited mutations in the PIEZO2 gene (otherwise known as PIEZO2- Deficiency Syndrome \[PDS\]). PIEZO2 encodes a stretch-gated ion channel whose function has been shown to be essential for aspects of gentle touch sensation, vibration detection, mechanical allodynia and proprioception in humans. The physiological effects of PIEZO2 mutations on sensory neurons in humans are unknown. The study will improve our understanding of the molecular mechanisms for touch and mechanical pain sensation and determine if the peripheral neurons remain otherwise healthy in the absence of a functioning PIEZO2 channel. Objectives: Primary Objective: To determine whether peripheral neurons have a blunted response to gentle mechanical stimulation (e.g., soft brushing) in PDS patients compared to healthy participants using direct electrical recording from peripheral nerves. Secondary Objectives: To examine the physiological properties of different types of mechanically sensitive sensory neurons in response to innocuous and noxious stimuli in PDS patients and healthy participants. We expect the loss of PIEZO2 to have greater impact on the responsiveness of certain types mechano-receptor subtypes over others. Endpoints: Primary Endpoint: Our primary endpoint is evidence of reduced responsiveness (i.e., firing rate \[Hz\]) of peripheral neurons to gentle mechanical (brushing) stimulation in PDS patients compared to controls. We expect a reduction of at least 50% in firing rate (Hz). Secondary Endpoints: Our secondary endpoint is the emergence of a differential effect of the loss of PIEZO2 on mechanoreceptor subclasses. Mechanoreceptor subclasses will be identified using established criteria (e.g., stimulus sensitivity, receptive field size, spike morphology and axon conduction velocity). The effect of the loss of PIEZO2 on the responsiveness of single-unit subclasses will be quantified by firing rate measures on single-unit data. In addition, the percept evoked to intraneural electrical stimulation of single-unit subclasses will be noted.
| Study Type : | OBSERVATIONAL |
| Estimated Enrollment : | 16 participants |
| Official Title : | Microneurographic Assessment of Peripheral Nerves in Healthy Volunteers and Individuals With Sensory Dysfunction Caused by Inherited Mutations in the PIEZO2 Gene |
| Actual Study Start Date : | 2024-11-26 |
| Estimated Primary Completion Date : | 2026-12-31 |
| Estimated Study Completion Date : | 2026-12-31 |
Information not available for Arms and Intervention/treatment
| Ages Eligible for Study: | 18 Years to 100 Years |
| Sexes Eligible for Study: | ALL |
| Accepts Healthy Volunteers: | 1 |
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Not yet recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892