Cellular transplantation for Parkinson’s disease: a strategy whose time has passed

Alterman, Ron L.

doi:10.3171/2021.1.jns203748

Cited by 2 publications

(2 citation statements)

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“…For instance, Dr. Ron Alterman recently voiced his criticisms on the first case report describing a patient treated with autologous mDAPs for PD in the following ways: 1) past cell therapy trials have failed despite promising open-label phase 1 studies, 2) the placebo effect may account for some aspects of these failures, 3) side effects such as graft-induced dyskinesia were another cause of trial failure, and 4) not all underlying pathophysiological mechanisms of PD are addressed by cell therapy. 170,171 Although the starting point for these criticisms is that cell therapy will likely provide no more effective symptom control than is currently available with proven therapies, such as DBS and dopamine medications, 172 presently this is unknown, and ongoing investigations will help clarify this matter. Nevertheless, a conceptual advantage of stem cell-based therapy is that this approach alleviates parkinsonian symptoms (such as DBS or dopamine pharmacotherapy) as well as restores synapse formation and dopamine turnover between transplanted cells and preserved host neurons and rescues both motor and nonmotor deficits in PD patients.…”

Section: Discussionmentioning

confidence: 99%

“…Despite this progress, there are some concerns regarding cell transplantation therapy for PD. For instance, Dr. Ron Alterman recently voiced his criticisms on the first case report describing a patient treated with autologous mDAPs for PD in the following ways: 1) past cell therapy trials have failed despite promising open-label phase 1 studies, 2) the placebo effect may account for some aspects of these failures, 3) side effects such as graft-induced dyskinesia were another cause of trial failure, and 4) not all underlying pathophysiological mechanisms of PD are addressed by cell therapy [ 170 , 171 ]. Although the starting point for these criticisms is that cell therapy will likely provide no more effective symptom control than is currently available with proven therapies, such as DBS and dopamine medications [ 172 ], presently this is unknown, and ongoing investigations will help clarify this matter.…”

Section: Discussionmentioning

confidence: 99%

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Current Status and Future Perspectives on Stem Cell-Based Therapies for Parkinson’s Disease

Cha

Park

Leblanc

et al. 2023

JMD

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Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting 1%–2% of the population over the age of 65. As the population ages, it is anticipated that the burden on society will significantly escalate. Although symptom reduction by currently available pharmacological and/or surgical treatments improves the quality of life of many PD patients, there are no treatments that can slow down, halt, or reverse disease progression. Because the loss of a specific cell type, midbrain dopamine neurons in the substantia nigra, is the main cause of motor dysfunction in PD, it is considered a promising target for cell replacement therapy. Indeed, numerous preclinical and clinical studies using fetal cell transplantation have provided proof of concept that cell replacement therapy may be a viable therapeutic approach for PD. However, the use of human fetal cells remains fraught with controversy due to fundamental ethical, practical, and clinical limitations. Groundbreaking work on human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, coupled with extensive basic research in the stem cell field offers promising potential for hPSC-based cell replacement to become a realistic treatment regimen for PD once several major issues can be successfully addressed. In this review, we will discuss the prospects and challenges of hPSC-based cell therapy for PD.

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Section: Discussionmentioning

confidence: 99%