Study of ALS Reversals 2: Genetic Analyses

Amyotrophic Lateral Sclerosis (ALS) is a devastating motor neuron disease that typically
causes rapidly progressive muscle weakness, disability and premature death. In spite of a
large number of attempted ALS trials, there are no significant disease-modifying therapies
for this condition to-date.

There exists a small group of patients who meet diagnostic criteria for ALS or progressive
muscular atrophy (PMA), progress for a period of time, and then significantly improve. Some
of these "ALS reversals" even make a complete recovery back to normal neurological function.
The investigator has independently verified 34 of these cases so far through review of
medical records and peer-reviewed literature. These patients are different in their
demographics and disease characteristics as compared to patients with more typically
progressive ALS. One possible explanation for these cases is that these patients are
genetically different than most patients with ALS and that these differences confer a form of
disease "resistance". Study of these selected reversal patients may yield valuable clues to
endogenous mechanisms of ALS resistance. The concept of genetic conferred ability to resist a
disease is not novel. A group of patients who could unexpectedly "control" HIV due to a
mutant allele has led to an improved understanding of HIV pathophysiology and a new treatment

This is a pilot case-control study attempting to discover genetic correlates to ALS
reversals. The investigator will collect demographics, disease characteristics, pedigree
information and saliva samples from ALS reversals. Whole genome DNA will be extracted and
sequenced from these saliva samples. The genomes of ALS reversals will then be compared with
whole genome sequencing previously completed from a biorepository of de-identified samples of
more typically progressive patients with ALS. The study will not save any saliva samples
collected as a part of this new protocol for future research.

Inclusion Criteria:

1. Prior participation in Documentation of Known ALS Reversals (Duke IRB Pro00076395)

2. Confirmation of ALS or PMA (primary muscular atrophy) diagnosis through medical record
review (previously documented in Documentation of Known ALS Reversals protocol)

3. Sustained, robust improvement on at least one objective ALS outcomes measure (ex.
ALSFRS-R, FVC, strength testing, EMG) (previously documented in Documentation of Known
ALS Reversals protocol)

4. Able to understand English

Exclusion Criteria:

1. History of cognitive impairment severe enough to preclude informed consent, reported
by patient on direct questioning or as suspected by research personnel from
Documentation of Known ALS Reversals (Duke IRB Pro00076395) study data

2. Prior participation in the Phenotype Genotype and Biomarkers in ALS and Related
Disorders (RDCRN #8001) protocol