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September 28, 2020
A team of investigators from McLean Hospital and Massachusetts General Hospital (MGH) reported that reprogramming a patient’s own skin cells to replace cells in the brain that are progressively lost during Parkinson’s disease (PD) is technically feasible.
PD is the second most common neurodegenerative disease of the brain, and millions of people worldwide experience its symptoms, which include tremor, stiffness, and difficulty with speech and walking. The progressive loss of brain cells called dopaminergic neurons plays a major role in the disease’s development. As described in the current report, the use of a patient’s own reprogrammed cells is an advance that overcomes barriers associated with the use of cells from another individual.
“Because the cells come from the patient, they are readily available and can be reprogrammed in such a way that they are not rejected on implantation.
This represents a significant milestone in ‘personalized medicine’ for Parkinson’s,” said senior author Kwang-Soo Kim, PhD, director of the Molecular Neurobiology Laboratory at McLean Hospital, the largest clinical neuroscience and psychiatric affiliate of Harvard Medical School.
The McLean-MGH team reprogrammed skin cells from 69-year-old George Lopez, MD, to embryo-like pluripotent stem cells (called induced pluripotent stem cells) and then differentiated them to take on the characteristics of dopaminergic neurons, which are lost in Parkinson’s. After extensive testing of the cells, Kim applied to the FDA for a single-patient, investigational new drug application and also received the approval of the human subjects ethical review board for two hospitals to implant the cells into Lopez’s brain.
Bob Carter, MD, PhD, chief of Neurosurgery at MGH and co-senior author, said: “This strategy highlights the emerging power of using one’s own cells to try and reverse a condition—Parkinson’s disease—that has been very challenging to treat. I am very pleased by the extensive collaboration across multiple institutions, scientists, physicians, and surgeons that came together to make this a possibility.”
In a series of two separate surgeries in 2017 and 2018 at Weill Cornell Medical Center and MGH, Lopez, a former internist who was diagnosed almost two decades ago, underwent transplantation of the replacement dopamine neurons. Jeffrey Schweitzer, MD, PhD, a Parkinson’s specialized neurosurgeon and director of the Neurosurgical Neurodegenerative Cell Therapy program at MGH, designed a novel minimally invasive neurosurgical implantation procedure to deliver the cells, working in collaboration with Carter at MGH and Michael G. Kaplitt, MD, PhD, a neurosurgeon at Weill Cornell.
Two years later, imaging tests indicate that the transplanted cells are alive and functioning correctly as dopaminergic neurons in the brain.
Kim noted, “We have shown for the first time in this study that these reprogrammed cells are recognized by the patient’s immune system and won’t be rejected.” These results indicate that this personalized cell-replacement strategy was a technical success, with the cells surviving and functioning in the intended manner. Lopez has not developed any side effects, and there are no signs that the cells have caused any unwanted growth or tumors.
“Doc,” as Lopez likes to be called, said that in the time that has passed since surgery, he has enjoyed improvements in his day-to-day activities and significant improvement in his quality of life. Routine activities, such as tying his shoes, walking with an improved stride, and speaking with a clearer voice, have become possible again. Some activities—such as swimming, skiing, and biking, which he had given up years ago—are now back on his agenda.
Drs. Kim and Lopez first met in 2013, after which Doc began following Dr. Kim’s research and supporting it philanthropically. “I never thought I would benefit from this research,” he said. “It’s been fascinating to be part of such pioneering medicine, and the McLean and MGH teams have been fantastic to work with. I hope and believe that—as their work progresses—others will benefit too.”
Kim cautioned, “While it is very encouraging, this single-patient study does not prove the safety or the efficacy of this personalized therapy. We definitely need more careful and formal clinical trials to address it.”
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