Neural Tissue Xenotransplantation: What is Needed Prior to Clinical Trials in Parkinson's Disease?

2000 ◽  
Vol 9 (2) ◽  
pp. 235-246 ◽  
Author(s):  
Roger A. Barker ◽  
A. Lisa Kendall ◽  
Håkan Widner ◽  
H. Widner ◽  
L. Larsson ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Human Tissue ◽  
Neural Tissue ◽  
Fetal Tissue ◽  
Suitable Material ◽  
Human Fetal Tissue ◽  
Critical Issues ◽  
Alternative Sources

Embryonic allografted human tissue in patients with Parkinson's disease has been shown to survive and ameliorate many of the symptoms of this disease. Despite this success, the practical problems of using this tissue coupled to the ethical restrictions of using aborted human fetal tissue have lead to an exploration for alternative sources of suitable material for grafting, including xenogeneic embryonic dopaminergic-rich neural tissue. Nevertheless, xenografted neural tissue itself generates a number of practical, ethical, safety, and immunological issues that have to be addressed prior to any clinical xenotransplant program. In this article we review these critical issues and set out the criteria that we consider need to be met in the development of our clinical xenotransplantation research programs. We advocate that these, or similar, criteria should be adopted and made explicit by other centers contemplating similar clinical trials.

Utility of Fragmented Human Fetal Tissue as a Potential Dopaminergic Brain Graft in Parkinson's Disease

1993 ◽  
Vol 61 (1) ◽  
pp. 1-11 ◽  
Author(s):  
R.I. HogenEsch ◽  
M.J. Staal ◽  
I.P. Kema ◽  
C.H.C.M. Buys ◽  
K.G. Go
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Fetal Tissue ◽  
Human Fetal Tissue

Transplantation of Human Fetal Tissue from Spontaneous Abortions to a Rodent Model of Parkinson's Disease

1996 ◽  
Vol 5 (1) ◽  
pp. 69-75 ◽  
Author(s):  
Takeshi Kondoh ◽  
Lisa L. Pundt ◽  
Jeffrey P. Blount ◽  
John A. Conrad ◽  
Walter C. Low
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Transplantation ◽  
Functional Expression ◽  
Fetal Tissue ◽  
Growth Potential ◽  
Functional Improvement ◽  
Spontaneous Abortions ◽  
Nigrostriatal Pathway ◽  
Human Fetal Tissue

The use of human fetal tissue from elective abortions for cell transplantation therapies has been the subject of considerable controversy. Because of concerns regarding the use of tissue from elective abortions, tissue from spontaneous abortions has been suggested as an alternate donor source. In the present study we have evaluated human fetal tissue from spontaneous abortions to assess its viability, growth potential, and functional expression. Viable cells (Grade I) from a donor (7 wk postconception) were transplanted as a suspension into the striatum of rats with unilateral 6-OHDA lesions of the nigrostriatal pathway. A second group of animals received solid grafts of tissue from a Grade I donor 14 wk postconception. Tissue from Grade II and III specimens were not sufficiently viable for transplantation. Locomotor responses were monitored over a period of 15 wk and revealed an amelioration of rotational asymmetry by animals that received tissue from the 7 wk donor. Animals receiving tissue from the 14 wk donor showed no functional improvement. We found numerous graft-derived tyrosine hydroxylase (TH) immunopositive neurons contained within the transplantation site, and a rich plexus of TH-immunopositive fibers extending into the striatum of animals receiving tissue from the 7 wk donor. Animals receiving tissue from the 14 wk donor exhibited tissue necrosis at the transplant site and were devoid of TH-immunopositive neurons. These results suggest that human fetal ventral mesencephalic cells from spontaneous abortions can survive and develop after transplantation, and rectify locomotor deficits associated with experimental parkinsonism if the donor tissue is of the appropriate gestational age at the time of implantation. Our study further suggests, however, that the availability of tissue from spontaneous abortions of sufficient viability is quite limited and may thus restrict its potential use in cell transplantation therapies for Parkinson's disease.

Critical issues of the biopsychosocial treatment of Parkinson’s disease

2015 ◽  
Vol 156 (12) ◽  
pp. 472-478 ◽  
Author(s):  
Péter Kincses ◽  
Norbert Kovács ◽  
Kázmér Karádi ◽  
János Kállai
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Psychological Health ◽  
Interdisciplinary Approach ◽  
Cognitive Status ◽  
Psychological Burden ◽  
Her Family ◽  
Critical Issues

This paper is a summary report on the basic questions of the biopsychosocial approach to Parkinson’s disease. It deals with cognitive, affective and psychological health issues which significantly influence the outcome of the physical rehabilitation. In spite of the unchanged cognitive status, the psychological burden of the changes in the quality of life, the obstruction, the change in the affective tone, and the shrinking ability to fulfil social roles decrease the patient’s quality of life. An interdisciplinary approach is best suited for mitigating these effects. Not only the patient but also his/her family and environment is seriously affected by the disease and its consequences. Treatment and rehabilitation options for increasing or maintaining the quality of life of the affected patients are diverse, and significantly depend on the features of the health care system. The authors believe that the following review emphasizing health psychological principles may contribute to the work of professionals working in clinical and rehabilitational fields and through them may increase the quality of life of patients and their family. Orv. Hetil., 2015, 156(12), 472–478.

scholarly journals Bringing Advanced Therapies for Parkinson’s Disease to the Clinic: The Scientist’s Perspective

2021 ◽  
pp. 1-6
Author(s):  
Mark Tomishima ◽  
Agnete Kirkeby
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Phase I Clinical Trials ◽  
Preclinical Models ◽  
Preclinical Development ◽  
Dopaminergic Medication ◽  
Gene Therapies ◽  
Advanced Therapies ◽  
New Phase

After many years of preclinical development, cell and gene therapies have advanced from research tools in the lab to clinical-grade products for patients, and today they constitute more than a quarter of all new Phase I clinical trials for Parkinson’s disease. Whereas efficacy has been convincingly proven for many of these products in preclinical models, the field is now entering a new phase where the functionality and safety of these products will need to stand the test in clinical trials. If successful, these new products can have the potential to provide patients with a one-time administered treatment which may alleviate them from daily symptomatic dopaminergic medication.

Neuroprotective agents for clinical trials in Parkinson's disease: A systematic assessment

Neurology ◽  
2003 ◽  
Vol 60 (8) ◽  
pp. 1234-1240 ◽  
Author(s):  
B.M. Ravina ◽  
S.C. Fagan ◽  
R.G. Hart ◽  
C.A. Hovinga ◽  
D.D. Murphy ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Neuroprotective Agents ◽  
Systematic Assessment

Parkinson's disease and convergence insufficiency: a mini-review

2021 ◽  
Vol 1 (3) ◽  
pp. 108-111
Author(s):  
Mashael Al-Namaeh
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Control Group ◽  
Healthy Controls ◽  
Inclusion Criteria ◽  
Medline Search ◽  
Convergence Insufficiency ◽  
Eye Examination ◽  
The Relationship

Background: A key manifestation of Parkinson’s disease (PD) is visual impairment. Cognitive impairment has been found to overlap with convergence insufficiency (CI) in patients with PD and is associated with significantly greater near point convergence (NPC) distance. Difficulty in reading and diplopia were the most common symptoms of CI in PD. The prevalence of CI is greater among patients with PD. Therefore, this study aimed to assess the relationship between PD and CI. Methods: Studies that had included data on CI, NPC, or both were selected by searching PubMed/MEDLINE and clinicaltrails.gov, without any timeline or language limitation. The following terms were used in PubMed/MEDLINE search: ‘Clinical Trials’, ‘Parkinson’s Disease’, and ‘Convergence Insufficiency’. For clinical trials.gov database, the terms ‘Parkinson’s Disease’, ‘Convergence Insufficiency’, and ‘Completed Studies’ were used. Only those studies with control subjects were included. PubMed/MEDLINE search yielded 1,563 articles, but no article was found in the clinical trails.gov search. Twelve articles met the inclusion criteria, among which nine articles were selected as they had data on CI or NPC distance (cm), and PD.   Results: Overall, there were 1,563 articles; among them, 12 articles met the inclusion criteria. Nine articles were selected based on their data concerning CI or NPC distance (cm) and PD. Relative to the control group, the PD group had high CI. In addition, PD group showed increase in NPC distance than the control group. Conclusions: These data suggest that the patients with PD had an increased likelihood of developing CI visual symptoms, and increased NPC distance than healthy controls. These findings indicate that regular eye examination is very important for patients with PD.

Longitudinal Change and Progression Indicators Using the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale in Two Independent Cohorts with Early Parkinson’s Disease

2021 ◽  
pp. 1-16
Author(s):  
Michael Bartl ◽  
Mohammed Dakna ◽  
Sebastian Schade ◽  
Tamara Wicke ◽  
Elisabeth Lang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Rating Scale ◽  
De Novo ◽  
Longitudinal Change ◽  
Single Center ◽  
Square Roots ◽  
Disease Rating

Background: The MDS-Unified Parkinson’s disease (PD) Rating Scale (MDS-UPDRS) is the most used scale in clinical trials. Little is known about the predictive potential of its single items. Objective: To systematically dissect MDS-UPDRS to predict PD progression. Methods: 574 de novo PD patients and 305 healthy controls were investigated at baseline (BL) in the single-center DeNoPa (6-year follow-up) and multi-center PPMI (8-year follow-up) cohorts. We calculated cumulative link mixed models of single MDS-UPDRS items for odds ratios (OR) for class change within the scale. Models were adjusted for age, sex, time, and levodopa equivalent daily dose. Annual change and progression of the square roots of the MDS-UDPRS subscores and Total Score were estimated by linear mixed modeling. Results: Baseline demographics revealed more common tremor dominant subtype in DeNoPa and postural instability and gait disorders-subtype and multiethnicity in PPMI. Subscore progression estimates were higher in PPMI but showed similar slopes and progression in both cohorts. Increased ORs for faster progression were found from BL subscores I and II (activities of daily living; ADL) most marked for subscore III (rigidity of neck/lower extremities, agility of the legs, gait, hands, and global spontaneity of movements). Tremor items showed low ORs/negative values. Conclusion: Higher scores at baseline for ADL, freezing, and rigidity were predictors of faster deterioration in both cohorts. Precision and predictability of the MDS-UPDRS were higher in the single-center setting, indicating the need for rigorous training and/or video documentation to improve its use in multi-center cohorts, for example, clinical trials.

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