Longitudinal Study of Innate Lymphoid Cells in Peripheral Blood in ALS

Application - HUM00107546

Study Title:

Longitudinal Study of Innate Lymphoid Cells in Peripheral Blood in ALS

Full Study Title:

Longitudinal Study of Innate Lymphoid Cells in Peripheral Blood in ALS

If there are other U-M studies related to this project, enter the eResearch ID number (HUM#)
or IRBMED Legacy study number. Examples of related projects include, but are not limited to:

00028826 - Epidemological Risk Factors and The Genetics of ALS

Principal Investigator:

- Benjamin Murdock, PhD

Study Team Members:

- Eva Feldman, MD, PhD Co-Investigator

- Stephen Goutman, MD Co-Investigator

- Claudia Figueroa-Romero, Research Investigator

- Crystal Pacut, Biorepository Coordinator

- Jayna Duell, Study Coordinator

- Blake Swihart, Study Coordinator

- Benjamin Segal, MD Consultant

- Adam Patterson, Biostatistician

Project Summary:

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized
by progressive muscle weakness and eventual death. Studies demonstrate that the immune system
plays a key role in ALS progression; however, the role of the immune system is unclear, as
various aspects can play both a beneficial and detrimental role in the disease course.
Attempts to universally suppress the immune system in ALS patients have at best had
negligible effects on progression or at worst accelerated the disease. Alternatively,
augmenting or depleting specific immune cell populations in ALS mouse models alters the
disease course and slows progression. Thus, there is a critical need to identify immune cell
populations to serve as biomarkers and therapeutic targets.

Neuroinflammation is a hallmark of ALS in both human patients and mouse models. While
clinical symptoms result from motor neuron degeneration, it is becoming increasingly clear
that the immune system plays a key role in pathology. A variety of insults give rise to
identical immune responses which go on to produce the characteristic clinical and
histopathological manifestations of motor neuron disease. This makes the immune system an
attractive target for therapeutics, as the wide variety of potential ALS sources all funnel
through a common immunological pathway over the course of disease. The investigators recent
studies have demonstrated that ALS patients have increased levels of several subpopulations
of innate lymphoid cells (ILCs) in their peripheral blood. A subset of patients has ILC
levels 5-10 times greater than those found in healthy control patients. The differences seen
in the ILC levels in peripheral blood are much greater differences seen in other immune cell
populations during ALS. Thus, these cell populations are attractive candidates for use as
biomarkers or therapeutic targets.

The proposed study can be broken into three broad phases which will applicable to each
patient: recruitment, sample collection, and analysis. Following diagnosis of disease, ALS
patients who live within 1 hour of the University of Michigan will be called by our clinical
coordinator and enrolled in the study (recruitment). Following enrollment in the study, each
of the patients will be visited once every 28 ± 3 days for a year after the initial visit by
a Michigan Institute for Clinical & Health Research (MICHR) clinical research unit; this unit
will take 10 ml of blood per patient. Samples will then be returned to the University of
Michigan. ILCs will be isolated from peripheral blood using fluorescence-activated cell
sorting (FACS) and the mRNA of each ILC population will be collected and cytokine production
analyzed using multiplex (analysis). On the day of collection, a clinician or clinical
coordinator from the University of Michigan Comprehensive ALS Clinic (UMCAC) will contact the
patient to complete an ALSFRS-R questionnaire to assess the physical deterioration of the
patients.

The study will also incorporate control subjects. The control subjects will have blood taken
once a month for 12 months, but will not complete the ALSFRS-R questionnaire as they will not
have been diagnosed with ALS and therefore the questionnaire does not fit. 10ml of blood will
be taken per visit.

Inclusion Criteria:

- Age 18 years or older.

- Clinically definite, probable, probable laboratory supported, or possible ALS by El
Escorial criteria

- Fluency in English at the 6th grade level or higher.

- Able to communicate sufficiently well by speaking

- Able to communicate over the phone.

- Capable of providing informed consent.

- Lives geographically accessible to the University of Michigan

Exclusion Criteria:

- Unable to provide informed consent.

- Clinically significant dementia, as judged by the site investigator.

- Other neurological or psychiatric disorders which are expected to impair cognitive
function.

- Other serious and uncontrolled medical disorders.

- History of autoimmune disease.

- Use of prednisone, IVIG, or immunosuppression within the last 12 months.

- Not geographically accessible to the University of Michigan