IBMPFD Research Study – University of Kentucky Medical Center

Researchers at the University of Kentucky Medical Center are trying to better understand IBMPFD through clinical studies with members of IBMPFD families. IBMPFD is caused by alterations (mutations) in the valosin-containing protein, VCP. We are working within a network of researchers from across the country led by Dr. Virginia Kimonis at the University of California, Irvine.

At the University of Kentucky, we are focusing on why some individuals with VCP mutations develop dementia, and others, even within the same family, do not develop dementia. There must be some factor other than the VCP mutation itself that determines whether a given individual will have dementia as a part of IBMPFD. So far we have found that another gene besides VCP, apolipoprotein-E, that seems to modify the risk of dementia in some families. We are looking to discover other such factors.

Dementia is a general term for impairments in memory, language, and judgment due to altered brain function. Dementia is not a disease, but rather is a description of a group of symptoms. Different diseases may cause the symptoms included under the term "dementia". In IBMPFD, impairments involve language and judgment particularly, a pattern termed frontotemporal dementia (FTD – the "FD" part of IBMPFD) because the particular brain regions involved are the frontal and temporal lobes. These frontal and temporal regions have specific roles in making judgments, planning actions for the future, and in language expression

Research Available at the University of Kentucky

Through funding from the National Institute on Aging and the University of Kentucky General Clinical Research Center, we are bringing in family members from across the country for two types of studies performed over two days:

(1) We study brain function using functional-magnetic-resonance-imaging (fMRI). fMRI allows us to see what parts of the brain are particularly active during performance of tasks such as remembering alphabet letters over a short period of time. We also perform testing of language, memory, and judgment using standardized tests and inventories. Even family members who do not show any signs of the disease can have the same fMRI imaging and testing for comparison. The goals of the study are to demonstrate effects of IBMPFD on brain function, and to find factors predicting dementia in individuals with VCP alterations.

(2) We study the clinical status of individuals with a series of medical tests: clinical examination of muscle strength, electrical study of muscle function, and heart function using echocardiograms. Samples of muscle, skin, and blood are collected for use by basic science researchers to further study the genetics of IBMPFD. An important goal of this sample collection is to make material available worldwide to the scientific community so that more researchers have the opportunity to make progress in understanding IBMPFD. We do this by sending samples to the Coriell Institute, an NIH-funded gene bank that has participation from hundreds of scientific laboratories around the world.

Personnel and Contact Information.

For more information about the study see "Details" below or call/email the study coordinator or principal investigator.

Study Coordinator: Barbara Martin

email: barbara.martin@uky.edu

Telephone: 859-323-0494

FAX: 859-323-1068

Principal Investigator: Charles D. Smith, MD

email: csmith@mri.uky.edu

Telephone: 859-323-1113

FAX: 859-323-1068

Bio-sketch: This is an outline of Dr. Smith's qualifications and training. (Dr. Charles Smith Biography)

More Details on the University of Kentucky IBMPFD Research

Research Project Description

This protocol is designed to collect data and specimens from members of families with IBMPFD, a rare autosomal dominant genetic disorder causing frontotemporal dementia (in some cases), inclusion body myopathy, and Paget disease of bone. Data and specimens are sent to research laboratories for molecular and genetic studies with the ultimate goal of finding treatments for the disorder. It is done in parallel with an imaging study performed at UK-MRISC of the same subjects. Subjects are recruited from across the US and come to Lexington specifically for this research.

The study consists of two parts:

Part 1 is the imaging study, and consists of some paper and pencil tests of memory and thinking lasting about two hours. Then there is a special MRI scan where we "exercise" the brain by having you perform tasks, and determine changes in brain blood oxygen related to these tasks. You lie down in the scanner and watch a screen, performing some simple thinking tasks while the MRI is running. This takes about an hour in the MRI scanner. The study is funded by the National Institute of Health (NIH), which pays for transportation and lodging in Lexington, the testing, and the scan. The study cannot be done on other scanners, unfortunately; otherwise we would spare you the trip. The idea is to bring you in the night before the MRI, and perform the studies the next day.

Part 2 involves a second full day in the General Clinical Research Center (GCRC) in Lexington, and is designed to collect a standard set of information and research specimens from all participants. Blood will be drawn, a urine sample will be collected, and there will be an electromyogram (EMG), electrocardiogram (EKG), and echocardiogram (echo). We will also have a punch skin biopsy and a muscle biopsy done by an experienced specialist to get tissue that can be used by Dr. Kimonis for some sophisticated research funded by her NIH grant (micro-array RNA analysis). There will also be a brief physical examination. Participation in Part 2 is not necessary to participate in Part 1 (the imaging study); they are separate, but participation in at least Part 1 is required to be involved with the study. We hope that most everyone who does the imaging would also want to be involved in Part 2, but this is purely voluntary research and you are free to participate as you wish.

Research Consent: Imaging. This is a sample consent to provide further information on the imaging portion of the study (Part 1). We want you to read this ahead of time while you are home to make sure everything is acceptable before making the trek to Lexington. This consent is for information only – you do not need to sign it now, even if you want to participate. On arrival in Lexington, you would formally sign your consent form. (Consent Form Imaging Study)

Research Consent: Clinical Study. This is a sample consent to provide further information on the clinical portion of the study (Part 2). As with the imaging consent, we want you to read this ahead of time while you are home to make sure everything is acceptable before making the trek to Lexington. This consent is for information only – you do not need to sign it now, even if you want to participate. You must participate in Part 1(Imaging) to participate in Part 2 (Clinical). On arrival in Lexington, you would formally sign your consent form. (Consent Form Clinical Study)

HIPAA Authorization. These are permission forms you will need to sign describing privacy considerations when your name, birth date, or other identifying information is collected for a clinical study. (HIPPA Form 1, HIPAA Form 2)

About Genes and Inheritance. This document is a "refresher" that describes basic ideas about genes and heredity. (About Genes/Inheritance)

Considerations for Genetic Counseling. This document lists some of the considerations one should make when deciding whether to know if you carry a VCP mutation, and are therefore at risk of developing symptoms of IBMPFD. (Genetic Considerations)