Research is moving forward on a cellular level at Cedars-Sinai Medical Center’s Regenerative Medicine Institute in Los Angeles. Robert H. Baloh, MD PhD, Director of Neuromuscular Medicine, together with Patrick D. Lyden, MD, Chair of the Neurology Department, and Clive Svendsen, PhD, Institute Director, are studying disorders that originate in nerve cells. These include amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease), muscular dystrophies, and inherited peripheral nerve and muscle disorders such as Charcot-Marie-Tooth disease (CMT), one of the most common inherited neurological disorders.

Dr. Baloh and his team were awarded a three million dollar grant to develop induced pluripotent stem (iPS) cells with the goal of creating future treatments for these disorders. Dr. Baloh answered our questions about the research:

What are iPS cells?

Dr. Baloh: iPS (induced Pluripotent Stem) cells are stem cells derived from a patient’s own tissues that have the capability of transforming into a different cell type.

Why are stem cells important for studying and treating CMT?

Dr. Baloh: Stem cells are important for studying CMT because we can convert those iPS cells into neurons or Schwann cells (the cells that produce the myelin sheath protecting nerve fibers) and study them in the lab, or transplant them into an animal model, to determine what is going wrong and how to correct it. iPS cells are well suited for studying CMT because they come from patients and carry the exact genetic abnormality that causes the disease.

Stem cells could also play a role in treating CMT. In the future, we hope to use them to regenerate the nerve components that are abnormal in CMT.

How do you convert CMT1A cells to iPS cells?

Dr. Baloh: We take a small skin biopsy from patients, isolate dermal fibroblasts (the cells in skin that produce its fibrous structure), and then introduce a series of factors that “reprogram” those cells back to a stem cell state.

Why is cell differentiation important in stem cell research?

Dr. Baloh: A major first step in using stem cells to study or treat disease is converting iPS cells into the specific cell type relevant to that disease, such as a neuron or a Schwann cell. We try to recreate the signals those cells would normally receive during development in the body to guide them toward becoming that particular cell type.

Once stem cells are transplanted into a rat model with CMT1A, what changes do you look for?

Dr. Baloh: That is one of the biggest questions we need to answer. The goal is to differentiate the cells into Schwann cell precursors and then determine whether they engraft into the nerve, surround axons, form myelin, and provide trophic support for the axons. The central question is whether transplanting “fresh” genetically corrected Schwann cells into the nerves of the CMT rat model can support the survival of existing axons, slowing or stopping the loss of strength and sensation.

What is the timeline for this research?

Dr. Baloh: This grant is pre-clinical, meaning it involves developing a therapy before testing it in patients. Our hope is that within 3 to 5 years (the duration of the grant) we will be able to determine whether we can move forward to plan a Phase I clinical trial in patients.

Would a Phase I trial be the next phase of the project?

Dr. Baloh: Yes. The next phase would be to take iPS cells from CMT1A patients, genetically correct them by removing the extra copy of the PMP22 gene, convert those cells into Schwann cell precursors, and transplant them back into patient nerves. We would still need to determine how many transplants would be needed, where they would be placed, and at what stage of the disease the intervention should occur.

Do patients have to wait to participate? Who should they contact?

Dr. Baloh: CMT patients can participate right now by donating their skin cells, which requires only a small punch biopsy similar to those done by a dermatologist. Patients should contact the Cedars-Sinai CMT/Hereditary Neuropathy Center at (310) 423-4CMT. Our goal with the revitalized clinic is to combine improved genetic diagnosis and research opportunities with excellent multidisciplinary care.