PMD Clinical Trial

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The PMD Phase I safety study has completed it's enrollment and no more applicants will be accepted.

Illustration of how Pelizaeus-Merzbacher Disease (PMD) effects myelin In the winter of 2009/10, UCSF Benioff Children's Hospital will begin a Phase I safety study sponsored by StemCells, Inc. for a potential new therapy for connatal Pelizaeus-Merzbacher Disease (PMD), which is a rare inherited condition involving the central nervous system. Children with PMD are unable to form myelin. As a result, children have impaired function in language development and memory, and delayed motor skills seen as poor coordination and the inability to walk.

This study focuses on connatal PMD, the most severe type, which causes apoptosis (cell death) of oligodendrocytes, the cells which form myelin.

Learn more about Pelizaeus-Merzbacher Disease (PMD)

Download the Pelizaeus-Merzbacher Disease (PMD) Brochure [PDF 4.7MB]

Children found eligible for the study will undergo an operation that implants human central nervous system stem cells (HuCNS-SC® cells) into their brain. The study will examine whether HuCNS-SC® cells can be safely transplanted in children with a myelin disorder. The research is designed to see whether treatment with stem cells might one day help PMD patients. The HuCNS-SC® cells to be used in the trial are being supplied by StemCells, Inc.

Study Design

This study is coordinated through the University of California San Francisco Benioff Children’s Hospital (UCSF) and sponsored by StemCells, Inc. This study is is now open for enrollment. It is an open-label Phase I study that will enroll four (4) male subjects age six months to five years of age. To be eligible, children must be determined to have the connatal form of PMD confirmed with genetic testing, clinical symptoms and evidence of the disease based on radiology images (MRI). There are three main components of the study:

  1. The children will undergo an operation that will transplant human central nervous stem cells (HuCNS-SC® cells) into their brain.
  2. The children will be on medication (immunosuppression) for 9 months to prevent rejection of the transplanted stem cells.
  3. The children will undergo intensive follow-up for 1 year. They will have other studies done for 4 more years to check for any problems associated with the cells.

The procedures and most follow-up studies will all take place at UCSF in San Francisco, California. Travel and lodging arrangements for all visits to UCSF for the mother, father and child will be coordinated by the UCSF staff and paid for by the study. Expenses for meals will also be reimbursed.

Additional study design details can be found at PMD Trial FAQ. If you are interested in this study please contact our Trial Coordinator.

What does the study hope to accomplish?

cell lineage of neural stem cells This study will help doctors learn more about the safety of a potential new treatment for Pelizaeus-Merzbacher disease which uses human central nervous stem cells (HuCNS-SC® cells). This information will help determine whether further studies with these neural stem cells are safe and warranted in patients with the fatal forms of PMD. The primary endpoint for this study is safety. In other words, can human central nervous system stem cells be given to patients with the connatal form PMD without harmful effects? The enrolled children will undergo extensive follow-up for one year. In addition, families may be asked to participate in a four year long-term follow-up program.

Patient Evaluation & Enrollment Process

There will be four phases of the evaluation and enrollment process. Your child will need to be screened, first by telephone. If your child is found to be a possible candidate, further tests and screening will be needed in person in San Francisco. Prospective families, with a child with PMD, or their doctors can contact UCSF at 1-800-793-3887 for information and preliminary screening. The study will be explained and, if the family is interested and the child seems an appropriate study candidate the team at UCSF will ask for specific medical information.

Step I: Initial Screening for Eligibility

The purpose of the initial screening is to obtain information to determine if study requirements are met and the child is a candidate before the family travels to San Francisco. The doctors and nurses involved in the study are also available to discuss the details of the trial with the family over the telephone. They will ask for written consent to obtain the child’s medical records. Once the written consent is obtained, the medical records can be sent to UCSF for review by the study team. They should include.

  1. Written informed consent
  2. Child’s current medication list
  3. Physical exam and vital signs
  4. Medical history
  5. Head MRI and /or CT scan (reports and images)
  6. Recent blood lab work
  7. Results of genetic testing

Step II: Screening Evaluation at UCSF

If your child meets the study criteria and you wish to be considered for enrollment and treatment in the clinical trial, the next phase involves travel to UCSF for a formal evaluation. The evaluation will consist of meetings with the study team members and extensive testing of your child. These tests will take up to 3 days to complete. They will include:

  1. Review of medical chart, physical and neurological exam by Pediatric Neurologist
  2. Blood and urine samples
  3. Chest x-ray
  4. Electrocardiogram (ECG), measures heart function
  5. Magnetic Resonance Image (MRI), a non-invasive picture of brain and spine
  6. Electroencephalogram (EEG), measures seizure activity
  7. Evoked Potential (EP), records electrical response of specific sensory pathways
  8. Cognitive, speech/language, behavior and neurological testing
  9. Consultation with the following specialists:
    1. Neurosurgeon
    2. Transplant surgeon, an immuno-suppression specialist
    3. Anesthesiologist
    4. Ophthalmologist
    5. Radiologist

Main Inclusion Criteria

After your child’s full evaluation, eligibility for enrollment in the study will be determined by the criteria below. Complete details of the inclustion and exclusion criteria can be obtained from the study coordinator.

Inclusion Criteria
  • Male subjects:  from 6 months to 5 years of age.
  • Genetic testing confirms PLP1 gene mutation.
  • Reduced brain white matter & volume on MRI.
  • Confirmed clinical diagnosis of connatal PMD.
  • Ability of family to comply with follow-up and testing.
  • Family able to understand study and provide consent for their child.

What happens after enrollment?

Step III: Enrollment

If after all of the screening exams and procedures the study investigators find your child eligible to enroll in the study and you choose to continue, your child will be enrolled in the study. You will return home and be contacted by the study team to go over the next steps. The return trip to UCSF for the stem cell transplant will take place within 3 months of the screening. Planning for the surgery and stay in San Francisco will be arranged by the nurse study coordinators. The stay in San Francisco for the surgery will be at least 4 weeks time – 1 week in the hospital and 3 weeks at a hospital family housing facility. You will receive an information packet which outlines what to expect.

Step IV: Follow-up

After the surgery, you and your child will return to UCSF at regularly scheduled intervals over a one year period. These will occur at 2, 3, 6, 9, 10, and 12 months after the stem cells are transplanted. At those visits your child will undergo a series of tests.  In addition, while you are at home your child will be on 2 medications (an immunosuppressive drug and an antibiotic) for nine months. These medications will be administered by you and monitored by study investigators/doctors. The study team at UCSF will be in close contact with your child’s medical team at home to monitor his/her condition.

Trial Coordinator Contact Information

PMD Brochure If you are interested obtaining more information on this trial please call us at 1-800-793-3887 to speak to our clinical trial coordinator or email PMD@ucsfmedicalcenter.org.

We also recommend that you download our Pelizaeus-Merzbacher Disease (PMD) Brochure [PDF 4.7MB]

Last updated 08-30-2012