Understanding Clinical Phenotype and Collecting Biomarker Samples in C9ORF72 ALS

Individuals diagnosed with ALS, who are confirmed to carry the Chromosome 9 Open Reading
Frame 72 (C9ORF72) gene mutation by CLIA-certified lab results, are eligible for enrollment.
Researchers want to understand the natural history of C9ORF72 related ALS in terms of
measures of rate of progression as well as understanding how the size of the hexanucleotide
repeat expansion influences disease parameters. The investigators hope that the intense study
of patients with the C9ORF72 mutation will ultimately help us develop treatments for this
common form of ALS.

Objectives:

- Enroll a total of 120 C9ORF72 ALS participants with known mutation at the time of
enrollment.

- Determine the C9ORF72 hexanucleotide repeat expansion size in all subjects

- Define ALS disease course

- Determine to what degree the disease course correlates with expansion size

- Collect biomarker samples (blood, DNA and CSF)

Eligibility:

- Adults over age 18 with known C9ORF72 ALS status

Design:

Participants will have up to 9 in-person visits (this includes two Optional visits for lumbar
puncture procedures) and 5 telephone interviews over 3 years. Each in-person visit may be
tied to a regular clinic visit if subject is local (except for the optional lumbar puncture
visits) or if the subject is from out of town one initial visit can be set up with all other
visits performed via a telephone call and medical records review.

At each in town visit, subjects will undergo a blood draw (optional lumbar puncture) and two
questionnaires (ALS Functional Rating Scale - revised ALSFRS-R) which measures motor function
and the ALS-Cognitive Behavioral Screen (ALS-CBS) which will detect signs of Frontal Temporal
Dementia and a breathing test to determine Slow Vital Capacity (SVC) measurements.

For out of town subjects - blood draws can be scheduled locally and sent to the study site
for analysis. The ALSFRS-R can be performed over the phone along with other study related
questions.

The C9ORF72 mutation is called a "dominant" mutation, which means that their children have a
50% chance of inheriting the gene. Most people who inherit the C9ORF72 mutation will develop
either ALS or the related disease called fronto-temporal dementia. However, it may be
possible for someone to test positive for the C9ORF72 gene mutation and never develop
symptoms. Furthermore, in addition to C9ORF72, there are many other gene mutations that can
cause ALS. This study will not test these other genes, and therefore a negative test result
for the C9ORF72 mutation will not exclude the possibility that you have a heritable form of
ALS.

In order to understand the natural history of C9ORF72 related ALS in terms of measures of
rate of progression, the investigators need to understand how the size of the hexanucleotide
repeat expansion influences disease parameters. A C9ORF72-focused clinical trial defining an
accurate historical control population, will be critical since there may not be enough
subjects for a placebo controlled trial. To be ready for upcoming therapeutic trials, the
investigators need to start the detailed characterization of the C9ORF72 patients
immediately.

Inclusion:

1. Males or females of any race aged 18 or older

2. Known positive C9ORF72 ALS status via CLIA-certified lab results.

3. Capable of providing informed consent and following study procedures. In the event
that an individual lacks the ability to provide informed consent, informed consent may
be sought from the individual's legal, surrogate representative.

4. Geographically accessible to the site.

Exclusion:

1. Geographically inaccessible to the site

2. C9ORF72 ALS negative via CLIA-certified lab results