iPSC-derived dopamine progenitor cell therapy in Parkinson’s disease
Researchers optimize maturity and dose of induced pluripotent stem cell (iPSC)–derived dopamine progenitor cells for the treatment of Parkinson’s disease.
A collaborative team of researchers from Rush University Medical Center (IL, USA), FUJIFILM Cellular Dynamics, Inc. (WI, USA), Brooklyn ImmunoTherapeutics (NY, USA) and the Van Andel Institute (MI, USA) recently discovered the optimum maturity and dosage of iPSC-derived dopamine progenitor cells that successfully reversed 6-hydroxydopamine-induced hemiparkinsonism in rats.
Researchers used an adapted differentiation protocol to convert iPSCs into midbrain dopaminergic neurons of different maturities, cryopreserved at 17, 24 or 37 days of differentiation and engrafted these into immunocompromised hemiparkinsonian rats.
They discovered that engrafted midbrain dopamine progenitors that were cryopreserved at differentiation day 17 were significantly superior to progenitors engrafted at differentiation day 24 or 37 in their survival, fiber outgrowth and effects on motor symptoms.
The team then assessed different doses of these differentiation day 17 midbrain progenitors, using a range of 7500 to 450,000 injected cells per striatum, and found a clear dose response of surviving neurons, innervation and functional recovery. In addition to these results, no teratoma formation was observed in any of the rats.
“Patients with Huntington’s disease or multiple system atrophy or even Alzheimer’s disease could be treated in this way for specific aspects of the disease process,” commented the corresponding author, Jeffrey Kordower.
The use of iPSC-derived dopaminergic progenitor cell therapy will soon be tested in a clinical trial of patients with Parkinson’s disease caused by a mutation in the Parkin gene, to determine if these successful results will be translated.
“We cannot be more excited by the opportunity to help individuals who suffer from this genetic form of Parkinson’s disease, but the lessons learned from this trial will also directly impact patients who suffer from sporadic, or non-genetic forms of this disease,” Jeffrey Kordower said.
Source: Hiller BM, Marmion DJ, Thompson CA et al. Optimizing maturity and dose of iPSC-derived dopamine progenitor cell therapy for Parkinson’s disease. npj Regen Med. 7(24) (2022).