Intrathecal Autologous Adipose-derived Mesenchymal Stromal Cells for Amyotrophic Lateral Sclerosis (ALS)

The Goal of the Proposed Study is to perform an open label, 60 subject, Phase II multi-site
clinical trial to investigate the safety and efficacy of intrathecal treatment of aaMSCs in
ALS. Patients will be treated with 1 x 10^8 aaMSCs every 3 months for a total of 4
intrathecal injections over 12 months. Reduced dose treatments will be allowed based on
specific adverse events. Multiple biomarkers will be tracked throughout the clinical trial
and correlated with response to treatment. This study will initially be performed at Mayo
Clinic in Rochester. Subsequently, the study will expand to the two other Mayo Clinic sites
in Arizona and Florida as the manufacturing capabilities are finalized.

Inclusion Criteria:

- All patients will have ALS diagnosed as possible, laboratory-supported probable,
probable, or definite as defined by the World Federation of Neurology criteria for the
diagnosis of ALS.

- Examination and neurophysiological testing confirm a pure motor syndrome compatible
with the diagnosis of ALS. All other possible causes of weakness have been excluded by
extensive investigations.

- Age greater than 18 years, if female, must be post-menopausal, had a hysterectomy, or
agree to two forms of birth control.

- Permanent resident or citizen of the United States.

- Geographic accessibility to the study site and willingness and ability to comply with
follow-up.

- History of a chronic onset of a progressive motor weakness of less than two years
duration.

- Subjects must be taking a stable dose of riluzole for at least 30 days prior to
enrolment or not be on riluzole, and not have been on it for at least 30 days prior to
enrolment (riluzole-naïve subjects are permitted in the study).

- Able to comply with protocol requirements, including MRI testing.

- Can provide written informed consent.

Exclusion Criteria:

- Any clinically significant medical condition (e.g., within six months of baseline, had
myocardial infarction, angina pectoris, and/or congestive heart failure) that, in the
opinion of the investigator, would compromise the safety of patient.

- Pulmonary Slow Vital Capacity (SVC) less than 65% of predicted for age, gender, and
body type.

- Autoimmunity, including Crohn's disease or rheumatoid arthritis

- Current use of immunosuppressant medication or use of such medication within 4 weeks
of Screening visit (Visit 1).

- Malignancy 5 years prior to enrollment, including melanoma,with the exception of
localized skin cancers (with no evidence of metastasis, significant invasion, or
re-occurrence within three years of baseline).

- Active systemic or local infection near the lumbar puncture site.

- Inability to lie flat for the duration of intrathecal cell transplantation, or
inability to tolerate study procedures for any other reason.

- Other active systemic disease as defined by laboratory abnormalities delineated in
Appendix IV.

- Use of herbal medications or other unapproved drugs

- Enrolled in an investigational drug trial within 30 days of baseline visit

- Prior stem cell therapy of any kind

- Kokmen Short Test of Mental Status score <32

- Presence of a tracheostomy

- Ventilator dependent

- Pregnancy

- Men or women of childbearing potential who are unwilling to employ adequate
contraception