Are We Getting Closer to a Cure for Parkinson"s?
Updated October 12, 2014.
How can you treat a disease when you don’t even know what it is? Researchers are increasingly realizing that many of degenerative “diseases” such as Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis are actually groups of many diseases that end up causing similar symptoms.
Parkinson’s disease is a good example of a “disease” that is in fact several diseases in one. The term is generally used to mean when someone has two of the four following symptoms: tremor, rigidity, postural instability, and slow movement.
In addition, the person must respond to treatment with levodopa. In reality, though, this just describes a group of symptoms, which may be caused by different things. For example, fever and chills can be caused by several different viruses or bacteria, each requiring different treatment.
Neurologists have had some success in treating the symptoms of Parkinson’s disease, but not the underlying cause. This is like treating a fever with Tylenol, but not treating the virus causing the sickness. The lack of overall success in addressing the underlying cause of Parkinson’s may be in part due to the mix of different causes. What may work for one cause of Parkinson’s disease may not work for another.
Future Treatments for Parkinson's Symptoms
Current treatments of Parkinson’s disease focus on motor complications such as tremor and rigidity. Further trials are being performed with tozadnant and istradefylline. Some movement problems such as dyskinesia, however, remain difficult to treat. Dyskinesia often results from fluctuation in levodopa levels with current medications.
More constant drug levels might prevent these movement side effects. Intestinal infusion of levodopa gel has shown a marked decrease in side effects while maintaining benefits against parkinsonism, for example. Continuous subcutaneous apomorphine has demonstrated similar effects, though skin nodules may result as well as other side effects. Efforts to achieve a long-acting oral formulation of L-dopa continue.
Amantadine has some evidence behind it in treating dyskinesia, though the trials were small. Safinamide is a MAO-B inhibitor that may improve both off-time and dyskinesia, and may be approved for the market soon. Trials are being planned for AFQ056 and nicotine receptor agonists.
While movement disorders are the most prominent features of Parkinson’s disease, many other neurological problems also develop. At this point, few drugs are on the horizon to treat disorders such as dementia in Parkinson’s disease.
Fixing Neurodegeneration
The holy grail of Parkinson’s research, and indeed most research of neurodegenerative disease, is a drug that not only addresses the symptoms caused by the disease, but that can protect the brain itself against further changes, or event reverse the damage that has been done. No drug has been shown to be clearly neuroprotective, though there are some lingering hopes for selegiline and rasagiline, which require further investigation.
Trophic factors naturally encourage growth of neurons, but trials delivering such factors into the brain have not yet proven successful. Whether this is due to improper delivery or a problems with the factor itself is unknown.
The brains of people with Parkinson’s disease have been shown to have increased inflammation, problems with mitochondrial function, oxidative stress and excitotoxicity. Clinical trials of agents aimed at these targets have been unsuccessful. It may be that multiple factors contribute to the cascade, so that a cocktail of different treatments would be required in the same way that is often used in the treatment of HIV or some cancers. Some of this toxicity is mediated by calcium channels, and medications that block calcium channels are now being tested in Parkinson’s. Anti-inflammatory therapies have been suggestive of benefit in models of parkinson’s disease, but only one anti-inflammatory agent has been tested in a double-blind trial, and failed.
Nuclear receptor related 1 protein is a transcription factor that regulates dopamine neurons development and survival. The factor is reduced in PD. Several groups are investigating ways to stimulate Nurr1.
Genetic mutations have offered insights into PD treatment. LRRK2 mutations are the most common cause of genetic PD, though the mechanisms behind this are incompletely mapped out. Parkin nad PINK1 mutations are associated with mitochondrial dysfunction. Rapamycin has been shown to protect fruit-flies expressing PINK or parkin mutations. Other medications that have tried to enhance mitochondrial function, such as CoQ10 failed in trials. Creatine and a modified form of CoQ10, are under investigation. Resveratrol promotes mitochondrial genesis, and protects against PD in some animal models.
In short, while we don't yet have a cure for Parkinson's disease, it's not for lack of trying, and several promising approaches are now underway. For more information about clinical trials, speak with a medical professional for opportunities near you.
Sources:
CW Olanow and AHV Schapira: Therapeutic prospects for Parkinson's Disease. Annals of Neurology, Volume 74, Issue 3, pages 337, September 2013
How can you treat a disease when you don’t even know what it is? Researchers are increasingly realizing that many of degenerative “diseases” such as Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis are actually groups of many diseases that end up causing similar symptoms.
Parkinson’s disease is a good example of a “disease” that is in fact several diseases in one. The term is generally used to mean when someone has two of the four following symptoms: tremor, rigidity, postural instability, and slow movement.
In addition, the person must respond to treatment with levodopa. In reality, though, this just describes a group of symptoms, which may be caused by different things. For example, fever and chills can be caused by several different viruses or bacteria, each requiring different treatment.
Neurologists have had some success in treating the symptoms of Parkinson’s disease, but not the underlying cause. This is like treating a fever with Tylenol, but not treating the virus causing the sickness. The lack of overall success in addressing the underlying cause of Parkinson’s may be in part due to the mix of different causes. What may work for one cause of Parkinson’s disease may not work for another.
Future Treatments for Parkinson's Symptoms
Current treatments of Parkinson’s disease focus on motor complications such as tremor and rigidity. Further trials are being performed with tozadnant and istradefylline. Some movement problems such as dyskinesia, however, remain difficult to treat. Dyskinesia often results from fluctuation in levodopa levels with current medications.
More constant drug levels might prevent these movement side effects. Intestinal infusion of levodopa gel has shown a marked decrease in side effects while maintaining benefits against parkinsonism, for example. Continuous subcutaneous apomorphine has demonstrated similar effects, though skin nodules may result as well as other side effects. Efforts to achieve a long-acting oral formulation of L-dopa continue.
Amantadine has some evidence behind it in treating dyskinesia, though the trials were small. Safinamide is a MAO-B inhibitor that may improve both off-time and dyskinesia, and may be approved for the market soon. Trials are being planned for AFQ056 and nicotine receptor agonists.
While movement disorders are the most prominent features of Parkinson’s disease, many other neurological problems also develop. At this point, few drugs are on the horizon to treat disorders such as dementia in Parkinson’s disease.
Fixing Neurodegeneration
The holy grail of Parkinson’s research, and indeed most research of neurodegenerative disease, is a drug that not only addresses the symptoms caused by the disease, but that can protect the brain itself against further changes, or event reverse the damage that has been done. No drug has been shown to be clearly neuroprotective, though there are some lingering hopes for selegiline and rasagiline, which require further investigation.
Trophic factors naturally encourage growth of neurons, but trials delivering such factors into the brain have not yet proven successful. Whether this is due to improper delivery or a problems with the factor itself is unknown.
The brains of people with Parkinson’s disease have been shown to have increased inflammation, problems with mitochondrial function, oxidative stress and excitotoxicity. Clinical trials of agents aimed at these targets have been unsuccessful. It may be that multiple factors contribute to the cascade, so that a cocktail of different treatments would be required in the same way that is often used in the treatment of HIV or some cancers. Some of this toxicity is mediated by calcium channels, and medications that block calcium channels are now being tested in Parkinson’s. Anti-inflammatory therapies have been suggestive of benefit in models of parkinson’s disease, but only one anti-inflammatory agent has been tested in a double-blind trial, and failed.
Nuclear receptor related 1 protein is a transcription factor that regulates dopamine neurons development and survival. The factor is reduced in PD. Several groups are investigating ways to stimulate Nurr1.
Genetic mutations have offered insights into PD treatment. LRRK2 mutations are the most common cause of genetic PD, though the mechanisms behind this are incompletely mapped out. Parkin nad PINK1 mutations are associated with mitochondrial dysfunction. Rapamycin has been shown to protect fruit-flies expressing PINK or parkin mutations. Other medications that have tried to enhance mitochondrial function, such as CoQ10 failed in trials. Creatine and a modified form of CoQ10, are under investigation. Resveratrol promotes mitochondrial genesis, and protects against PD in some animal models.
In short, while we don't yet have a cure for Parkinson's disease, it's not for lack of trying, and several promising approaches are now underway. For more information about clinical trials, speak with a medical professional for opportunities near you.
Sources:
CW Olanow and AHV Schapira: Therapeutic prospects for Parkinson's Disease. Annals of Neurology, Volume 74, Issue 3, pages 337, September 2013
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