Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

September 5, 2008 updated by: Assistance Publique - Hôpitaux de Paris

Genetic Linkage in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD) is a rare clinical entity, in which both disorders are variably associated in the same patient or within the family. This adult-onset disorder, which is rapidly fatal, occurs in some families with autosomal dominant (AD) transmission and age-dependant penetrance. Two studies have provided evidence for linkage of this condition to chromosomes 15 (in a single family) and 9 (in five families). However, none of these loci have been yet confirmed. Through a national network of 10 centres with specialists for FTD and/or ALS, we have identified 35 probands with ALS-FTD, including 13 with a family history consistent with AD inheritance.

Mutations in the SOD1 and tau genes, respectively responsible for autosomal dominant forms of ALS and FTD, will be excluded by direct sequencing. We will then extend the pedigree of the 13 autosomal dominant families to all consenting first, second and eventually third degree relatives, using well defined criteria for FTD and ALS. The same strategy will be applied to newly identified families during the course of the project (at least, seven families with AD inheritance expected). Linkage studies will be performed in the 20 families using markers from the two candidate regions on chromosomes 9 and 15. Then, refinement of the candidate region will be obtained by analyzing the linked families with a high density of microsatellite markers. This should lead to the refinement of the candidate regions, allowing to search for mutations in candidate genes. Genes located within the critical regions will be prioritized for their analysis by sequencing, according to their expression in the nervous system and to their function.

Once the responsible gene(s) will be identified, it will then possible to define its spectrum of mutations and to establish genotype/phenotype correlations. Alternatively, if none of the candidate regions is confirmed, a genome wide search will be performed, allowing to identify one or more loci for ALS-FTD. The same strategy would then be applied to identify the corresponding gene(s). This project should contribute for identifying the molecular basis of this devastating disorder with practical consequences for genetic counselling in ALS-FTD families, and with the perspective of elucidating the pathophysiology of this disorder.

Study Overview

Status

Terminated

Conditions

Detailed Description

The objective of this study without direct individual benefit is to confirm the linkage with one or another region of the two identified regions (chromosomes 9 and 15) or to identify a new implicated chromosomal region, and then to reduce the linkage interval in order to identify the responsible gene(s) and characterize the mutations with the study of at least 9 families with FTD and ALS.

Study Type

Observational

Enrollment (Actual)

400

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Caen, France, 14000
        • CHU de la cote de Nacre
      • Lille, France, 59000
        • Centre Hospitalier Universitaire de Lille
      • Marseille, France, 13005
        • Hôpital La Timone
      • Marseille, France, 13009
        • Hôpital Sainte-Marguerite
      • Nantes, France, 44000
        • Hopital Guillaume Et Rene Laennec
      • Nice, France, 06000
        • Hopital de l'Archet
      • Paris, France, 75013
        • Hôpital Pitié-Salpêtrière
      • Paris, France, 75013
        • Hôpital Pitié-Salpêtrière - Centre du Langage-Neuropsychologie
      • Paris, France, 75013
        • Hôpital Pitié-Salpêtrière - Fédération de Neurologie
      • Rennes, France, 35000
        • Hôpital Pontchaillou
      • Rouen, France, 76000
        • Hopital Charles Nicolle
      • Saint-Brieuc, France, 22000
        • Centre Hospitalier
      • Saint-Etienne, France, 42000
        • Hopital Bellevue
      • Strasbourg, France, 67000
        • Hôpital Civil
      • Toulouse, France, 31000
        • Hopital Purpan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients and relatives coming in outcome clinics. They are all volunteers and agree to give a blood sample and signing an informed consent explaining the study.

Description

Inclusion Criteria:

  • ALS with FTD, "pure" FTD but with knowledge of relatives with ALS-FTD or "pure" ALS, "pure" ALS but with knowledge of relatives with ALS-FTD or "pure" FTD (not carriers of a mutation in the tau and SOD1 genes), relatives signing the informed consent

Exclusion Criteria:

  • Minors, persons refusing to sign the informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
1
Patients with frontotemporal dementia and amyotrophic lateral sclerosis
2
Relatives (first and second degree) of patients presenting an association of frontotemporal dementia with amyotrophic lateral sclerosis

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2002

Study Completion (Actual)

June 1, 2007

Study Registration Dates

First Submitted

September 7, 2005

First Submitted That Met QC Criteria

September 7, 2005

First Posted (Estimate)

September 12, 2005

Study Record Updates

Last Update Posted (Estimate)

September 8, 2008

Last Update Submitted That Met QC Criteria

September 5, 2008

Last Verified

September 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRC01107
  • P011023

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Amyotrophic Lateral Sclerosis

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Turkmenistan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe