by University of Technology, Sydney
Credit: Pixabay
A drug that provides the benefits obtained from medicinal cannabis without the "high" or other side effects may help to unlock a new treatment for Parkinson's disease.
The drug—HU-308—lessens devastating involuntary movements called dyskinesias, a side effect from years of treatment for Parkinson's disease.
The research, published today in Neurobiology of Disease, has been conducted by the Centre for Neuroscience and Regenerative Medicine (CNRM) at the University of Technology Sydney (UTS) and the Applied Medical Research Institute of St Vincent's Hospital Sydney.
The study shows that in mice HU-308 is as effective as amantadine, the only available treatment for dyskinesias. Furthermore, the combination of HU-308 with amantadine is more effective than either drug used alone.
Professor Bryce Vissel, director of the CNRM and senior author of the study, said the findings present the possibility of new options for Parkinson's patients.
"Our study suggests that a derivative of HU-308, either alone or in combination with amantadine, may be a more effective treatment for dyskinesias and a much better option than using an unproven potentially harmful substance like cannabis," Professor Vissel said.
"Currently there is limited evidence about the effectiveness of medicinal cannabis. One problem is that no cannabis preparation is the same and cannabis has numerous effects, some of which may not be beneficial in Parkinson's disease."
Cannabis works on several receptors in the brain—CB1 and CB2. The psychoactive effect is caused mostly because of receptor CB1.
Professor Vissel said the HU-308 drug explored by his team works only on receptor CB2, allowing medicinal benefits to be administered without causing psychoactive effects like drowsiness or highness.
Lead author Dr. Peggy Rentsch said it is unclear whether medicinal cannabis itself can help Parkinson's patients.
"Medicinal cannabis contains different compounds, some of which make you high and which can impact a person's normal day-to-day activities," Dr. Rentsch said.
"Our research suggests HU-308 is an important prototype drug which we believe won't interfere with patients' day-to-day activities. They should maintain normal levels of mental sharpness on a treatment like this."
Professor Vissel and his team are investigating ways to block inflammation of the brain to maintain and restore memory and slow the progression for both Parkinson's disease and Alzheimer's disease.
"HU-308 works by reducing inflammation in the brain, affecting the neurons and immune cells.
"In neurological disorders, the immune cells in the brain can lose supportive function with adverse stimuli—including but not limited to trauma or obesity—and become 'activated.' Scientists at the CNRM believe that, after this activation, the immune cells backfire, kill the brain's neurons, destroy them—and become dysfunctional.
"By reducing inflammation in the brain—such as with HU-308—these immune cells can support normal neural function again, rather than inhibiting it."
Study collaborator Dr. Sandy Stayte said: "The fact that amantadine has its own set of side effects, may not work in the long term, and is still the only drug available on the market that is approved for dyskinesias makes our study really exciting.
"First, our study shows HU-308 is equally affective so a drug like HU-308 will be useful for those people who can't take amantadine. Second, for those who can tolerate amantadine, taking the combination may have even greater benefits than taking either drug alone. That means we may end up with a much more powerful treatment than currently available by ultimately prescribing both."
The paper "Targeting the cannabinoid receptor CB2 in a mouse model of l-dopa induced Dyskinesia" is published in the journal Neurobiology of Disease.
A drug that provides the benefits obtained from medicinal cannabis without the "high" or other side effects may help to unlock a new treatment for Parkinson's disease.
The drug—HU-308—lessens devastating involuntary movements called dyskinesias, a side effect from years of treatment for Parkinson's disease.
The research, published today in Neurobiology of Disease, has been conducted by the Centre for Neuroscience and Regenerative Medicine (CNRM) at the University of Technology Sydney (UTS) and the Applied Medical Research Institute of St Vincent's Hospital Sydney.
The study shows that in mice HU-308 is as effective as amantadine, the only available treatment for dyskinesias. Furthermore, the combination of HU-308 with amantadine is more effective than either drug used alone.
Professor Bryce Vissel, director of the CNRM and senior author of the study, said the findings present the possibility of new options for Parkinson's patients.
"Our study suggests that a derivative of HU-308, either alone or in combination with amantadine, may be a more effective treatment for dyskinesias and a much better option than using an unproven potentially harmful substance like cannabis," Professor Vissel said.
"Currently there is limited evidence about the effectiveness of medicinal cannabis. One problem is that no cannabis preparation is the same and cannabis has numerous effects, some of which may not be beneficial in Parkinson's disease."
Cannabis works on several receptors in the brain—CB1 and CB2. The psychoactive effect is caused mostly because of receptor CB1.
Professor Vissel said the HU-308 drug explored by his team works only on receptor CB2, allowing medicinal benefits to be administered without causing psychoactive effects like drowsiness or highness.
Lead author Dr. Peggy Rentsch said it is unclear whether medicinal cannabis itself can help Parkinson's patients.
"Medicinal cannabis contains different compounds, some of which make you high and which can impact a person's normal day-to-day activities," Dr. Rentsch said.
"Our research suggests HU-308 is an important prototype drug which we believe won't interfere with patients' day-to-day activities. They should maintain normal levels of mental sharpness on a treatment like this."
Professor Vissel and his team are investigating ways to block inflammation of the brain to maintain and restore memory and slow the progression for both Parkinson's disease and Alzheimer's disease.
"HU-308 works by reducing inflammation in the brain, affecting the neurons and immune cells.
"In neurological disorders, the immune cells in the brain can lose supportive function with adverse stimuli—including but not limited to trauma or obesity—and become 'activated.' Scientists at the CNRM believe that, after this activation, the immune cells backfire, kill the brain's neurons, destroy them—and become dysfunctional.
"By reducing inflammation in the brain—such as with HU-308—these immune cells can support normal neural function again, rather than inhibiting it."
Study collaborator Dr. Sandy Stayte said: "The fact that amantadine has its own set of side effects, may not work in the long term, and is still the only drug available on the market that is approved for dyskinesias makes our study really exciting.
"First, our study shows HU-308 is equally affective so a drug like HU-308 will be useful for those people who can't take amantadine. Second, for those who can tolerate amantadine, taking the combination may have even greater benefits than taking either drug alone. That means we may end up with a much more powerful treatment than currently available by ultimately prescribing both."
The paper "Targeting the cannabinoid receptor CB2 in a mouse model of l-dopa induced Dyskinesia" is published in the journal Neurobiology of Disease.
by University of Aberdeen
Credit: CC0 Public Domain
Researchers from the University of Aberdeen have identified parts of a gene that could open the door to treatment with medical cannabis for millions of people.
Although promising, the potential of cannabinoids in treating disease, addiction and obesity has been hampered due to the unpredictability of adverse side-effects which can include depression and psychosis. At present there is no way to predict which people will experience these side-effects, but Dr. Alasdair MacKenzie and his team, including leading cannabis researcher Professor Roger Pertwee, are working towards making these predictions.
In a study published in Psychoneuroendocrinology, Dr. MacKenzie and Dr. Elizabeth Hay from the School of Medicine, Medical Science and Nutrition at the University, used revolutionary DNA sequencing, CRISPR technology to study specific areas of the gene that make cannabis receptors in the brain. According to their research, these previously ignored gene regions may hold the key to understanding why people respond differently to some drugs and could help inform treatments tailored to the individual.
Dr. MacKenzie explains: "We found that there was a genetic switch within the cannabis receptor in humans and mice and which had remained almost unchanged for hundreds of millions of years. This switch controlled the expression of the receptor in a part of the brain that modulates mood. We found that when we disrupted this switch in mice, alcohol intake and anxiety levels were reduced, as were the effects of cannabinoids.
"This means that we are helping to establish a functional role for this switch which may help us understand how it responds to cannabinoids. Going forward, this will contribute to unlocking the potential of medicinal cannabis."
Targeted drug therapy could dramatically increase the effectiveness of medicinal cannabis by eliminating the risk of harmful side-effects and this research has moved a step closer to that.
In a related study the team that were also able to identify a genetic change in the switch which occurred in about 20% of people. In a second paper published in Human Mutation, the team concluded that this may increase susceptibility to side effects in these individuals.
Dr. MacKenzie explains: "Cannabinoids are amazing source of drug therapies however the side effects that some people suffer hampers the development of these drugs. We need to know why people respond differently to drugs? Why do some people suffer depression and psychosis when taking cannabis when others don't? By identifying the people who could suffer from these adverse effects we could try to develop personalized medicine."
"It is hoped that this "gene switch" based approach may accelerate the development of more effective "personalized" cannabinoid-based drug treatments to treat obesity, addiction and mood disorders more safely. "
Professor Pertwee who is an internationally recognised leader in the therapeutic potential of cannabinoids added: "By starting to look at the effects of genetic changes on the switches that turn genes on and off in specific cells and at specific times, instead of changes in the genes themselves, we can begin to understand how drug side effects arise in different patient groups and focus treatment using these drugs on those who would most benefit. "
More information: Elizabeth . Hay et al. Disruption of an enhancer associated with addictive behaviour within the cannabinoid receptor-1 gene suggests a possible role in alcohol intake, cannabinoid response and anxiety-related behaviour, Psychoneuroendocrinology (2019). DOI: 10.1016/j.psyneuen.2019.104407
Elizabeth A. Hay et al. Disease‐associated polymorphisms within the conserved ECR1 enhancer differentially regulate the tissue‐specific activity of the cannabinoid‐1 receptor gene promoter; implications for cannabinoid pharmacogenetics, Human Mutation (2019). DOI: 10.1002/HUMU.23931
Journal information: Psychoneuroendocrinology
No comments:
Post a Comment