Trial designed to treat children with connatal Pelizaeus-Merzbacher disease (PMD): UCSF, February 2011

Sometimes, the rarest diseases provide the most critical insights. Pediatrician David Rowitch, MD, PhD, is leading a stem cell trial designed to treat children with connatal Pelizaeus-Merzbacher disease (PMD), an uncommon but fatal brain disorder.

It is UCSF’s first stem cell clinical trial in humans, and Rowitch has high hopes that his work will not only help those patients with severe PMD, a disease so rare that he estimates there are only 10 cases in the United States, but also that it will improve understanding of more common disorders like multiple sclerosis (MS) and cerebral palsy – and how they might be cured.

Both multiple sclerosis and PMD are myelin disorders. Myelin, made by oligodendrocyte cells in the brain, coats nerve fibers, allowing communication among neurons, which forms the basis of all activity in the brain. In MS, some oligodendrocytes are damaged and die; in PMD, they are defective and can’t make myelin at all.

In the trial, Rowitch is working with StemCells, Inc. of Palo Alto, whose proprietary neural stem cell precursors are being transplanted into four boys’ brains. In animal trials, these cells became oligodendrocytes. In the current trial, Rowitch said, scientists are asking questions regarding their safety.

“If you put neural stem cells into the brains of children with PMD, what will happen?” Rowitch asks. “Will it make them worse? Will it cause a tumor? What about the burden of immunosuppression? This is a five-year study to see if PMD patients will be adversely impacted by implanted cells. If the answer is no, then what is the efficacy? Is it helping?” Rowitch believes the answers to these questions will be answered, allowing the field to progress to the next level.

Several departments at UCSF together recruited Rowitch, a Howard Hughes Medical Institute investigator, from Harvard University four years ago. “David Rowitch is a world expert in myelinating oligodendrocytes, with an interest in the diseases such as multiple sclerosis in which they are affected, as well as the tumors [brain cancer] that they can give rise to,” says Arnold Kriegstein, MD, PhD, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

Kriegstein wanted Rowitch to fill a key role in stem cell research. At the same time, Mitchel S. Berger, MD, chairman of the UCSF Department of Neurological Surgery, wanted him for brain cancer research, and Sam Hawgood, MBBS, now dean of the UCSF School of Medicine, recruited Rowitch to lead the Division of Neonatology and the Intensive Care Nursery.

Rowitch headed west to help establish the Newborn Brain Research Institute at UCSF, which includes the nation’s first Neurological Intensive Care Nursery. He simultaneously joined the stem cell center, where he conducts his basic research on oligodendrocytes and how they can be affected in human disease.

In the Neurological Intensive Care Nursery, cameras are set up to watch for seizures, and neurologists and neonatologists work closely together and with the latest therapies – such as a counterintuitive hypothermic “deep chill” that helps preserve brain cells in infants who lacked adequate oxygen during childbirth.

“The reasons you want a unit like this are twofold,” Rowitch says. “First, to do a better job in the short term. This will be a new standard of care in neonatology. Everyone is going to want to do this. Second, in science, we have new therapies coming out, and you are going to need a place to do that, where you have sophisticated monitoring capabilities.”

Rowitch finds his life as a clinician-scientist rewarding, giving him the opportunity to make discoveries in the lab as well as start a new brain-protective program that Kriegstein says is unique in the country.

Rowitch especially enjoys having so many great minds to call on for assistance. “We can bring in Arnold Kriegstein or Arturo Alvarez-Buylla, stem cell biologists who can ask incisive questions, challenge investigators and offer a very sophisticated level of review,” he says. “And we can bring in other basic science investigators who can ask some of the right questions about these therapies. This was the direction that I wanted to move in.”


4 thoughts on “Trial designed to treat children with connatal Pelizaeus-Merzbacher disease (PMD): UCSF, February 2011

  1. My 4 year old granddaughter has been diagonosed with PMD and I understand it is very rare for a girl to have pmd.Her parents don’t want to just watch their daughter slowly detiorate.What hope is out there for her?Please help us with some information.

  2. My 2 year old Grandson has PMD also, there really is no treatment out there yet all we can do is pray that this trial will result in a treatment or better yet a cure. If you are on facebook, there is a great group called “pelizaeus merzbacher disease, it’s rare but everywhere.” lots of great people with good info on there. I pray for all the children with PMD. God bless you.

  3. Siamo disperati,siamo italiani e nostro figlio è malato di PMD,lui ha 5 qualcuno ha qualche novità anche piccolissima e ci vuole contattare, la nostra mail è .Grazie di cuore

    Google Translate gave me this English translation of the above message:

    We are desperate, we are Italian and our son is sick of PMD, he has 5 years. If someone has some news too small and want to contact us, our email is Thank you

  4. Thank you for the comments. My heart goes out to all of you. I wish I could tell you more, but I think Susan’s suggestion of the Facebook group is the best idea:

    Best of luck to all of you.

    (I used Google Translate to put this message into Italian for Vito – I hope it works.)

    Grazie per i commenti. Il mio cuore va a tutti voi. Vorrei dirvi di più, ma credo che Susan suggerimento del gruppo di Facebook è la migliore idea:

    In bocca al lupo a tutti voi.

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