Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Imaging Epigenetic Dysregulation in Patients with Low Back Pain

Award Number: UH3AR076741
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/26/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2026

Group Awards By:

View Award Description

Imaging Epigenetic Dysregulation in Patients with Low Back Pain - Project Summary / Abstract Chronic pain is a complex disorder affects both physical and mental functioning and could compromise quality of life. Treatment for chronic pain is far from satisfactory because of the aversive effects associated with opioid medications. It is known that the development and maintenance of pain are mediated in the central nerves system; however, the pathophysiological causes contributing to pain remain to be determined. Neuroepigenetic mechanisms have been linked to the development and maintenance of pain through preclinical models of inflammatory and neuropathic pain. One family of epigenetic enzymes, known as histone deacetylases (HDACs), are being considered as therapeutic targets due to the analgesic responses achieved through HDAC inhibitors. Inhibition of HDACs leads to symptom amelioration in experimental models of pain. However, there is limited evidence about HDAC density concerning human pain across the entire brain. We have recently achieved a significant research goal by resolving a PET imaging agent, [11C]Martinostat, that selectively binds to a subset of HDAC enzymes. Our imaging studies to date, including more than 40 healthy human volunteers, have identified key features that make [11C]Martinostat a rare and promising HDAC probe including robust brain uptake and high specific binding. We are extremely excited to take a large step forward to develop [11C]Martinostat PET as a quantitative image biomarker for pain detection and diagnosis, with an ultimate goal of using [11C]Martinostat PET to monitor treatment responses. In this application, we propose a series of initial proof-of-concept clinical validation studies to evaluate if [11C]Martinostat PET is a sensitive biomarker to detect the typical (axial) chronic low back pain (cLBP). When successful, we will further explore the validity of using [11C]Martinostat PET to differentiate subtypes of pain by comparing [11C]Martinostat PET binding between axial cLBP with cLBP patients with radiculopathy. In addition, we plan to conduct a longitudinal study in sub-acute LBP patients (sLBP) to investigate whether there is unique imaging signature that differentiate patients who have convert to cLBP vs. those who recover from low back pain. We believe the research outlined in the proposal takes a robust and systematic approach to develop and validate [11C]Martinostat PET as a quantitative image biomarker for low back pain in patients. PET/MR imaging in humans with [11C]Martinostat will deliver answers to fundamental questions about chromatin modifying enzymes in the living human brain in a way that has not been possible until now. Importantly, using [11C]Martinostat to understand the alternation of HDAC expression in chronic pain patients will enable validation of an epigenetic drug target, refine patient selection based on HDAC expression, and facilitate proof of mechanism/target engagement in developing novel analgesics.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2021	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	12/9/2025	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2021	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	11/4/2024	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	8/30/2024	EXTENSION WITH OR WITHOUT FUNDS	$0
2024	2021	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	10/17/2023	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $1,152 )
2023	2021	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	6/1/2023	EXTENSION WITH OR WITHOUT FUNDS	$1,152
														Subtotal = $1,152

Issue Date FY: 2022 ( Subtotal = $287,871 )
2022	2021	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	2/14/2022	EXTENSION WITH OR WITHOUT FUNDS	$287,871
														Subtotal = $287,871

Issue Date FY: 2021 ( Subtotal = $1,899,288 )
2021	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	8/30/2021	EXTENSION WITH OR WITHOUT FUNDS	$1,899,288
														Subtotal = $1,899,288

Grand Total All Awards = $2,188,311

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Imaging Epigenetic Dysregulation in Patients with Low Back Pain

Award Number: UH3AR076741

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/26/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer