I gave a presentation to my neurology department on PREDICT-PD this week and, in preparation, my unsuspecting partner was put to use as a test audience. His first comment was - "You keep talking about identifying people for future Parkinson's Disease treatments, why aren't you developing a treatment???"
It's a good question, and this recent article, published in Drug Discovery Today, illuminates the issues around drug-development well. It calls for adopting a more human approach to developing treatments, focussing on human cells, tissues and subjects. Levodopa therapy for Parkinson's, which treats the symptoms but not the process that leads to cell damage, was introduced around 50 years ago. It was the result of investigations into the human brain and observations on the side effects of anti-dopaminergic substances. Since then, there has been very little progress in developing treatments which actually prevent the death of brain cells.
This article suggests that a focus on imperfect animal models has delayed progress - for example animal models often don't show the same side effects that humans do. No animal model has exactly the combination of brain damage and progressive symptoms we see with Parkinson's in humans and so promising results in animals have often not translated into humans. They discuss different therapeutic approaches - for example surgical approaches to repairing cells or DNA including stem cell treatments, gene therapy and peptide therapy, suggesting the need to observe results in human cells and tissues. They go on to discuss the use of computer-based techniques to model the potential interactions between new molecules and human systems as well as the detrimental effects of toxic molecules. Finally, they mention the importance of imaging techniques to monitor disease progression before symptoms develop.
The key to the success of all of these techniques is defining the right group of people to give treatments to, before they develop disease. Whilst the PREDICT-PD study may offer new insights into risk factors that could potentially suggest new therapies, it's main role will be in the selection of this group, in whom the benefits of treatment outweigh the risks. So, in a sense we are developing treatments, by playing a role in the bigger picture.
-Anna
https://www.sciencedirect.com/science/article/pii/S1359644618301442#bib1115
Parkinson's disease research: adopting a more human perspective to accelerate advances.
Marshall LJ, Willett C
Parkinson's disease (PD) affects 1% of the population over 60 years old and, with global increases in the aging population, presents huge economic and societal burdens. The etiology of PD remains unknown; most cases are idiopathic, presumed to result from genetic and environmental risk factors. Despite 200 years since the first description of PD, the mechanisms behind initiation and progression of the characteristic neurodegenerative processes are not known. Here, we review progress and limitations of the multiple PD animal models available and identify advances that could be implemented to better understand pathological processes, improve disease outcome, and reduce dependence on animal models. Lessons learned from reducing animal use in PD research could serve as guideposts for wider biomedical research.
It's a good question, and this recent article, published in Drug Discovery Today, illuminates the issues around drug-development well. It calls for adopting a more human approach to developing treatments, focussing on human cells, tissues and subjects. Levodopa therapy for Parkinson's, which treats the symptoms but not the process that leads to cell damage, was introduced around 50 years ago. It was the result of investigations into the human brain and observations on the side effects of anti-dopaminergic substances. Since then, there has been very little progress in developing treatments which actually prevent the death of brain cells.
This article suggests that a focus on imperfect animal models has delayed progress - for example animal models often don't show the same side effects that humans do. No animal model has exactly the combination of brain damage and progressive symptoms we see with Parkinson's in humans and so promising results in animals have often not translated into humans. They discuss different therapeutic approaches - for example surgical approaches to repairing cells or DNA including stem cell treatments, gene therapy and peptide therapy, suggesting the need to observe results in human cells and tissues. They go on to discuss the use of computer-based techniques to model the potential interactions between new molecules and human systems as well as the detrimental effects of toxic molecules. Finally, they mention the importance of imaging techniques to monitor disease progression before symptoms develop.
The key to the success of all of these techniques is defining the right group of people to give treatments to, before they develop disease. Whilst the PREDICT-PD study may offer new insights into risk factors that could potentially suggest new therapies, it's main role will be in the selection of this group, in whom the benefits of treatment outweigh the risks. So, in a sense we are developing treatments, by playing a role in the bigger picture.
-Anna
https://www.sciencedirect.com/science/article/pii/S1359644618301442#bib1115
Drug Discov Today. 2018 Sep 18. pii: S1359-6446(18)30144-2. doi: 10.1016/j.drudis.2018.09.010. [Epub ahead of print]
Parkinson's disease research: adopting a more human perspective to accelerate advances.
Marshall LJ, Willett C
Parkinson's disease (PD) affects 1% of the population over 60 years old and, with global increases in the aging population, presents huge economic and societal burdens. The etiology of PD remains unknown; most cases are idiopathic, presumed to result from genetic and environmental risk factors. Despite 200 years since the first description of PD, the mechanisms behind initiation and progression of the characteristic neurodegenerative processes are not known. Here, we review progress and limitations of the multiple PD animal models available and identify advances that could be implemented to better understand pathological processes, improve disease outcome, and reduce dependence on animal models. Lessons learned from reducing animal use in PD research could serve as guideposts for wider biomedical research.
In view of the wide range of work showing that PD starts in the gut and that PD can be modified /ameliorated by adjusting the gut bacteriome it must be the place to start the hunt for treatment. Patching with stem cells is a palliative not a remedy.
ReplyDeleteFurther recent discovery that AD can be reversed and that apoptosis of neurons is not as advanced early on as was supposed leads one to think that PD can be similarly treated.
Nutrition is a good place to start.