Dopaminergic progenitor cells derived from a Parkinson's disease patient's own skin cells and injected into his putamen showed evidence of survival and were associated with improved motor scores and quality of life measures.

The cells were implanted into the 69-year-old Parkinson's patient's putamen in two procedures, left hemisphere followed by right hemisphere, 6 months apart. PET imaging with a dopaminergic activity tracer up to 24 months suggested graft survival, reported Jeffrey Schweitzer, MD, PhD, of Massachusetts General Hospital, and colleagues, in the New England Journal of Medicine.

Over 24 months, the patient's MDS-UPDRS, part III (evaluating parkinsonian motor signs) and PDQ-39 (assessing Parkinson's disease-related quality of life) scores also improved. His Parkinson's drug regimen at 24 months was similar to his pre-procedure treatment, but his levodopa equivalents were reduced from 904 mg to 847 mg.

The patient required no immunosuppression. "We have shown for the first time in this study that these reprogrammed cells are still recognized as self by the patient's immune system and won't be rejected," senior author Kwang-Soo Kim, PhD, of McLean Hospital in Belmont, Massachusetts, said in a statement.

"The study is interesting and promising, but should be interpreted with caution given that it reports on only one patient with limited and incomplete clinical data," noted Malin Parmar, PhD, of Lund University's Developmental and Regenerative Neurobiology department in Sweden, who wasn't involved with the research.

"Nevertheless, it is an important milestone in the field as it reports on survival of stem cell-derived dopamine neurons in a human brain," she told MedPage Today.

"The study takes an autologous approach, where the patient's own cells are used for transplantation," Parmar noted. "It points to the feasibility of such an approach, but also the weaknesses associated with it relating to using different batches of cells for each transplant and each patient, which is likely to result in a high variation in outcome."

Cell replacement has been studied in Parkinson's disease for several decades. Fetal tissue-derived cell transplants have had variable outcomes, due in part to limitations of fetal tissue as a cell source and lack of standardization. Recent advances in developmental and stem cell biology have led to cell-replacement therapies involving dopamine neurons derived from human pluripotent stem cells.

In this study, researchers first performed a skin biopsy on the patient and harvested fibroblasts to generate lines of induced pluripotent stem cells (iPSCs), which were screened for pluripotent differentiation potential and to eliminate potentially harmful mutations.

They identified an iPSC clone capable of becoming midbrain dopaminergic progenitor cells (mDAPs) and guided its differentiation into 28-day mDAPs. The mDAP-derived neurons secreted dopamine and had electrophysiologic properties similar to substantia nigra dopaminergic midbrain neurons. The final cell product used for injection was then treated to eliminate undifferentiated iPSCs and ensure the absence of serotonergic cells that might contribute to graft-induced dyskinesia.

The patient had 4 million cells implanted in his left putamen and a similar injection on the right 6 months later. He was discharged after overnight observation for each procedure.

PET imaging at 24 months showed uptake bilaterally, greater on the right. A semi-quantitative change from baseline was reported as -4.0% to 13.5% on the right, and -4.8% to 9.8% on the left.

The researchers reported no adverse events. Over 24 months, the patient's PDQ-39 score (a quality of life measurement with a scale of 0 to 156; lower scores are better) improved from 62 from the time of his first injection to 2.

"Off" period MDS-UPDRS part III motor scores (on a scale of 0 to 132; higher scores are worse) were 43 at 4 weeks, and improved to 33 at 24 months. "On" motor scores were 38 at the time of first injection, and improved to 29 at 24 months.

Both the patient and raters knew about the intervention and this may have influenced motor and symptom scores, the researchers pointed out. A longer follow-up period may be needed to reach definitive conclusions about graft survival, they added.

"These results reflect the experience of one individual patient and a formal clinical trial will be required to determine if the therapy is effective," Schweitzer noted.

Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimers, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinsons, ALS, concussion, CTE, sleep, pain, and more. Follow

Disclosures

The research was supported by NIH grants, the philanthropic support of the Parkinson's Cell Therapy Research Fund at McLean Hospital and Massachusetts General Hospital, and the William and Elizabeth Sweet Endowed Professorship in Neuroscience at Harvard Medical School.

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Cell Therapy Shows Promise in Parkinson's - MedPage Today