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Patient-derived Dopamine Neurons Show Promise in Parkinson's Treatment

In This Article

  • Massachusetts General Hospital and McLean Hospital investigators created patient-derived dopaminergic neurons from induced pluripotent stem cells and implanted them into the brain of a patient with Parkinson's disease
  • The study is the first step in testing the safety and efficacy of this new Parkinson's disease treatment
  • Treatment eliminates the need for immunosuppression and overcomes ethical issues involved with the use of embryonic stem cells and fetal tissue
  • This new technique would be indicated for patients who have inadequate response to Parkinson's medications

Parkinson's disease is a neurodegenerative and movement disorder resulting, in part, from the death of dopamine-producing neurons in the brain. Symptoms include limb tremors, stiffness and rigidity, delayed intentional movement, disrupted balance and a forward-falling gait. There are no cures for Parkinson's disease.

A study published in the New England Journal of Medicine describes the treatment of a Parkinson's disease patient by Massachusetts General Hospital investigators, in collaboration with researchers from McLean Hospital, using patient-derived dopaminergic progenitor cells. Their novel technique transformed the patient's own stem cells into dopamine neurons that were implanted into the brain using minimally invasive methods.

These methods were developed through a collaboration between Jeffrey S. Schweitzer, MD, PhD, neurosurgeon, Todd M. Herrington, MD, PhD, director of Mass General's Deep Brain Stimulation Program, and Bob S. Carter, MD, PhD, chief of the Department of Neurosurgery, along with Kwang-Soo Kim, PhD, director of the Molecular Neurobiology Laboratory at McLean Hospital, whose laboratory made critical advances in methods for producing the implanted cells.

"We've made a significant step in personalizing the therapy, overcoming ethical issues and eliminating the need for immunosuppression," says Dr. Schweitzer. "Our work is grounds for cautious optimism, it's a new approach to an old problem."

Treating Dopaminergic Deficiency in Parkinson's Disease

In Parkinson's disease, there is death of dopamine-producing neurons in a region of the midbrain called the substantia nigra. Dopamine is an important regulator of activity in the basal ganglia network, which is critical for fine-tuning and executing movement. The symptoms of Parkinson's disease manifest in part because of altered basal ganglia activity.

No Parkinson's treatments are curative. Physicians use several effective approaches to control symptoms, such as medication, physical therapy and deep brain stimulation (DBS). Surgery for Parkinson's disease is indicated for patients who cannot tolerate medications or when they prove to be ineffective.

"Our Parkinson's Disease and Movement Disorders Clinic brings together a dedicated team of specialists, and together with the patient, we decide on the best treatment plan," says Dr. Herrington. "Our study is a first step towards offering a new item on the Parkinson's treatment menu. This option will appeal to the substantial amount of people who are inadequately treated with other available methods."

Dr. Herrington's research interest in understanding how deep brain stimulation affects movement disorders and basal ganglia function was foundational to the study. Investigators implanted engineered dopamine precursor cells into the striatum to restore dopaminergic innervation. It is thought that these cells help regularize the abnormal brain activity of Parkinson's disease.

Exploring Stem Cell-Based Treatments for Parkinson's Disease

The concept of restoring dopaminergic neurons in the brain has been around since the 1980s. "Initially they were using cells in the adrenal glands that make dopamine or cells derived from fetal tissues. But these are heterogeneous. It wasn't just dopamine cells, so it was hard to control what you were delivering to each individual," says Dr. Herrington.

Stem cells have renewed interest in this methodology. Mass General investigators have been able to turn stem cells into dopamine neurons in the laboratory, so the cells implanted in the brain are more controlled.

"Products made in the laboratory from stem cells are now more available, so we don't have to use human fetal tissue or other tissues that cause patients to need immunosuppression," says Dr. Schweitzer. "We replaced that missing dopamine in a more natural fashion."

Implanting Patient-Derived Dopaminergic Neurons into the Brain

The study's subject is a patient with idiopathic Parkinson's disease. Despite optimized medication therapy, he continued to experience significant motor symptoms.

Dr. Schweitzer and Dr. Carter implanted patient-derived midbrain dopaminergic progenitor cells in the patient using minimally invasive techniques. "Part of our goal in this project has been to improve and standardize that process to get the least trauma and the best survival of the cells," says Dr. Schweitzer.

Precise implantation of the cell grafts was aided by CT scans and MRI-guided stereotactic surgery. For the patient's safety, neurosurgeons implanted the cells in each side of the brain in two separate procedures spaced six months apart.

Mass General investigators produced the progenitor cells under strict, FDA-mandated good manufacturing practice conditions. The cells were derived from the patient's skin tissue.

"The real innovation is this personalized approach, combining clinical expertise in Parkinson's and the techniques that Dr. Kim's laboratory developed over many years," says Dr. Schweitzer. "Firstly, it solves a lot of ethical issues involved with embryonic stem cells and fetal tissue. The patient also did not require immunosuppressive drugs. Parkinson's patients tend to be an older population with other health problems. Our approach focuses on avoiding some of the complications that would otherwise be associated with any transplant therapy."

Measuring Symptom Improvement Using Subjective and Objective Measures

Two years after the surgeries, the patient has had no adverse events and reports improvements in daily function. Standardized examinations of motor functions also showed stabilization or improvement, and a PET scan suggested that the progenitor cells were making dopamine at the transplantation sites.

"This particular patient is an outdoor sports person and had to give up many of his favorite activities as the disease progressed," says Dr. Schweitzer. "It has been gratifying to see the patient regain ability and confidence in physical activities such as skiing and swimming that he has most appreciated throughout his life. "

As a caveat, however, investigators acknowledge that they and the patient were not blinded to the intervention. Under these circumstances, it is known from clinical research history in general, and in Parkinson's disease in particular, that there can be considerable placebo effects. As a result, Mass General researchers consider this study the first in a series of steps required to bring this therapy to the Parkinson's community. A larger, double-blind study is their next priority.

Dr. Herrington says there are several studies currently enrolling that will test other promising Parkinson's treatments as well. "We consider this a really exciting, technological breakthrough—but with a lot more work to do before it's ready for the clinic. We have great momentum now for these next stages, and we are laying the groundwork to get to a phase 1/2 clinical trial."

Dr. Carter notes, "Our goal has been to carefully lay the foundation for a new personalized cell therapy approach to Parkinson's disease. We've been fortunate to harness the energy of an outstanding team of neurosurgeons, neurologists and basic scientists to achieve this important milestone of treating our first patient."

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Mass General researchers report substantial clinical improvement in a patient with Parkinson's disease after they implanted midbrain dopaminergic progenitor cells that they differentiated in vitro from autologous induced pluripotent stem cells.


In this video, Jeffrey Schweitzer, MD, PhD, discusses his research using stem cell technology to restore normal function in patients with movement disorders. He believes this technology may be able to improve outcomes for patients with tremor, Parkinson's disease and dystonia.