Perspective: Treatment for Disease Modification in Chronic Neurodegeneration
Symptomatic treatments are available for Parkinson’s disease and Alzheimer’s disease. An unmet need is cure or disease modification. This review discusses possible reasons for negative clinical study outcomes on disease modification following promising positive findings from experimental research. I...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-04-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/10/4/873 |
| _version_ | 1797538030074986496 |
|---|---|
| author | Thomas Müller Bernhard Klaus Mueller Peter Riederer |
| author_facet | Thomas Müller Bernhard Klaus Mueller Peter Riederer |
| author_sort | Thomas Müller |
| collection | DOAJ |
| description | Symptomatic treatments are available for Parkinson’s disease and Alzheimer’s disease. An unmet need is cure or disease modification. This review discusses possible reasons for negative clinical study outcomes on disease modification following promising positive findings from experimental research. It scrutinizes current research paradigms for disease modification with antibodies against pathological protein enrichment, such as α-synuclein, amyloid or tau, based on post mortem findings. Instead a more uniform regenerative and reparative therapeutic approach for chronic neurodegenerative disease entities is proposed with stimulation of an endogenously existing repair system, which acts independent of specific disease mechanisms. The repulsive guidance molecule A pathway is involved in the regulation of peripheral and central neuronal restoration. Therapeutic antagonism of repulsive guidance molecule A reverses neurodegeneration according to experimental outcomes in numerous disease models in rodents and monkeys. Antibodies against repulsive guidance molecule A exist. First clinical studies in neurological conditions with an acute onset are under way. Future clinical trials with these antibodies should initially focus on well characterized uniform cohorts of patients. The efficiency of repulsive guidance molecule A antagonism and associated stimulation of neurogenesis should be demonstrated with objective assessment tools to counteract dilution of therapeutic effects by subjectivity and heterogeneity of chronic disease entities. Such a research concept will hopefully enhance clinical test strategies and improve the future therapeutic armamentarium for chronic neurodegeneration. |
| first_indexed | 2024-03-10T12:24:40Z |
| format | Article |
| id | doaj.art-fad464b62bde48a290630403d6d1810d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T12:24:40Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-fad464b62bde48a290630403d6d1810d2023-11-21T15:11:10ZengMDPI AGCells2073-44092021-04-0110487310.3390/cells10040873Perspective: Treatment for Disease Modification in Chronic NeurodegenerationThomas Müller0Bernhard Klaus Mueller1Peter Riederer2Department of Neurology, St. Joseph Hospital Berlin-Weissensee, Gartenstr. 1, 13088 Berlin, GermanyDepartment of Neurology, St. Joseph Hospital Berlin-Weissensee, Gartenstr. 1, 13088 Berlin, GermanyCenter of Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Würzburg, Margarete-Höppel-Platz 1, 97080 Würzburg, GermanySymptomatic treatments are available for Parkinson’s disease and Alzheimer’s disease. An unmet need is cure or disease modification. This review discusses possible reasons for negative clinical study outcomes on disease modification following promising positive findings from experimental research. It scrutinizes current research paradigms for disease modification with antibodies against pathological protein enrichment, such as α-synuclein, amyloid or tau, based on post mortem findings. Instead a more uniform regenerative and reparative therapeutic approach for chronic neurodegenerative disease entities is proposed with stimulation of an endogenously existing repair system, which acts independent of specific disease mechanisms. The repulsive guidance molecule A pathway is involved in the regulation of peripheral and central neuronal restoration. Therapeutic antagonism of repulsive guidance molecule A reverses neurodegeneration according to experimental outcomes in numerous disease models in rodents and monkeys. Antibodies against repulsive guidance molecule A exist. First clinical studies in neurological conditions with an acute onset are under way. Future clinical trials with these antibodies should initially focus on well characterized uniform cohorts of patients. The efficiency of repulsive guidance molecule A antagonism and associated stimulation of neurogenesis should be demonstrated with objective assessment tools to counteract dilution of therapeutic effects by subjectivity and heterogeneity of chronic disease entities. Such a research concept will hopefully enhance clinical test strategies and improve the future therapeutic armamentarium for chronic neurodegeneration. https://www.mdpi.com/2073-4409/10/4/873neurodegenerationrepulsive guidance molecule Aneuroprotectionrepairoxidative stressapoptosis |
| spellingShingle | Thomas Müller Bernhard Klaus Mueller Peter Riederer Perspective: Treatment for Disease Modification in Chronic Neurodegeneration Cells neurodegeneration repulsive guidance molecule A neuroprotection repair oxidative stress apoptosis |
| title | Perspective: Treatment for Disease Modification in Chronic Neurodegeneration |
| title_full | Perspective: Treatment for Disease Modification in Chronic Neurodegeneration |
| title_fullStr | Perspective: Treatment for Disease Modification in Chronic Neurodegeneration |
| title_full_unstemmed | Perspective: Treatment for Disease Modification in Chronic Neurodegeneration |
| title_short | Perspective: Treatment for Disease Modification in Chronic Neurodegeneration |
| title_sort | perspective treatment for disease modification in chronic neurodegeneration |
| topic | neurodegeneration repulsive guidance molecule A neuroprotection repair oxidative stress apoptosis |
| url | https://www.mdpi.com/2073-4409/10/4/873 |
| work_keys_str_mv | AT thomasmuller perspectivetreatmentfordiseasemodificationinchronicneurodegeneration AT bernhardklausmueller perspectivetreatmentfordiseasemodificationinchronicneurodegeneration AT peterriederer perspectivetreatmentfordiseasemodificationinchronicneurodegeneration |