The primary objective of this study is to determine the safety of intrathecal delivery of autologous mesenchymal stem cells (MSCs) to the cerebrospinal fluid (CSF) of patients with ALS using a dose-escalation study. The trial will include 25 adult, non-ventilator-dependent patients with clinically definite amyotrophic lateral sclerosis (ALS). Cells will be isolated from adipose tissue, expanded ex vivo and then, after ~8 weeks, intrathecal (IT) autologous delivery of MSCs will be performed. There will be 5 treatment groups of up to 5 patients each. Groups 1, 2, and 4 will receive a single dose of cells. Groups 3 and 5 will receive 2 doses of cells separated by 1 month. Groups will be completed sequentially so that patients will not be enrolled into the next treatment group until at least 3 patients in the preceding group have completed the treatment and 1 month of additional observation without significant toxicity. All patients will be followed on a regular basis until death or for a minimum of 2 years after completion of the final infusion. Initial clinical follow-up will be weekly with scheduled blood, CSF and magnetic resonance imaging (MRI) evaluations. After 1 month, patients will have clinical evaluations at 3 month intervals, or earlier if indicated by clinical status.
- All patients must have clinically-defined ALS as defined by the World Federation of Neurology criteria
- Age greater than 18 years
- If female, must be post-menopausal or had a hysterectomy
- Permanent resident or citizen of the United States
- History of a chronic onset of a progressive motor weakness of less than two years duration
- Able to comply with protocol requirements, including MRI testing
- Can provide written informed consent
- 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.
- Autoimmunity, including Crohn's disease, rheumatoid arthritis, psoriasis
- Malignancy including melanoma with the exception of localized skin cancers (with no evidence of metastasis, significant invasion, or re-occurrence within three years of baseline). Any other malignancy will not be allowed.
- Active systemic or local infection near the lumbar puncture site
- Other active systemic disease as defined by laboratory abnormalities
- Use of herbal medications or other unapproved drugs
- Enrolled in an investigational drug trial within 30 days of baseline visit
- Kokmen Short Test of Mental Status score <32
- Beck's Depression Inventory score >18
- Presence of a tracheostomy
- Ventilator dependent
Last updated: 05/29/2012