Letter to the Editor. Cell therapy for Parkinson’s disease

Abstract

Neurosurgical forumskeptics like Dr. Alterman who push the field to deliver an engineered cell product that is truly valuable to the patient. Given the rapid advances that are occurring in genomics and cell engineering globally, we see cell therapy for PD not as a therapy whose "time has passed" but rather a therapeutic approach whose time has only just begun.

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

“…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.…”

“…Furthermore, compared to the late 1990s fetal cell transplantation approaches, additional advantages of current PSC-based therapeutic approaches include: 1) novel strategies to reprogram cells (including the use of Nobel Prize-winning approaches for somatic cell reprogramming), 2) the practical ability to utilize PSCs with reduced or no graft rejection, and 3) systemic manufacturing methods to generate clinical-grade mDAPs and ensure their safety and efficacy before transplantation. 171 Although stem cell-based therapies for PD have some limitations (e.g., dopamine-related stem cell therapy may not correct all known nonmotor symptoms of PD resulting from nondopaminergic pathology; none of the cell-based therapies has yet undergone a successful phase 3 clinical trial), and the use of hPSC derivatives may continue to raise concerns about safety and feasibility, intensive scientific efforts have been committed -and are ongoing -to improve and further optimize the hPSC-based cell therapeutic approach to make it safer, more efficient, and less costly. Continuing effort, including both basic and clinical investigations, into a deeper understanding of PD etiology is imperative to translate our discoveries into novel therapeutic avenues to treat both motor and nonmotor PD symptoms.…”

“…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.…”

“…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. Furthermore, compared to the late 1990s fetal cell transplantation approaches, additional advantages of current PSC-based therapeutic approaches include: 1) novel strategies to reprogram cells (including the use of Nobel Prize-winning approaches for somatic cell reprogramming), 2) the practical ability to utilize PSCs with reduced or no graft rejection, and 3) systemic manufacturing methods to generate clinical-grade mDAPs and ensure their safety and efficacy before transplantation [ 171 ]. Although stem cell-based therapies for PD have some limitations (e.g., dopamine-related stem cell therapy may not correct all known nonmotor symptoms of PD resulting from nondopaminergic pathology; none of the cell-based therapies has yet undergone a successful phase 3 clinical trial), and the use of hPSC derivatives may continue to raise concerns about safety and feasibility, intensive scientific efforts have been committed – and are ongoing – to improve and further optimize the hPSC-based cell therapeutic approach to make it safer, more efficient, and less costly.…”