Medicine Long Used for Respiratory Ills Seen to Help Parkinson’s Patients in Small Trial

Parkinson's study results

A medicine approved in the late 1970s to clear the respiratory tract and thin mucus can also cross the blood-brain barrier and possibly protect cells there from the damage seen in Parkinson’s disease, a small Phase 2 clinical trial has found.

The study detailing these results, “Ambroxol for the Treatment of Patients With Parkinson Disease With and Without Glucocerebrosidase Gene Mutations – A Nonrandomized, Noncontrolled Trial,” was published in JAMA Neurology.

Mutations in the GBA gene are one of the most common genetic risk factors for Parkinson’s. The GBA gene contains instructions to produce an enzyme, called beta-glucocerebrosidase (GCase), that is active in lysosomes — special compartments within cells that break down and recycle different types of molecules.

When the GCase enzyme fails to work as it is supposed to, toxic substances like abnormal alpha-synuclein accumulate inside dopamine-producing neurons, leading to the inflammatory and neurodegenerative processes that are observed in Parkinson’s.

In theory, boosting GCase activity through the “repurposing” of this medicine could slow disease progression.

Repurposed medicines are those approved to treat diseases other than that now under study (in this case, Parkinson’s). Because their mechanisms of action and safety are known to differing degrees, the expensive and lengthy process of discovering and testing a new compound is typically not necessary.

Ambroxol (brand names are Mucosolvan, Mucobrox, and Mucol, among others) has been used worldwide for decades to treat respiratory diseases associated with sticky or excessive mucus, and is known to boost beta-glucocerebrosidase activity.

But for it to work in the context of Parkinson’s, it needs to reach the brain and central nervous system. This means it needs to cross the blood-brain barrier, the semi-permeable membrane that protects the brain from the external environment. This barrier often blocks medicines from being carried into the brain.

Researchers at the University College London Institute of Neurology designed an open label, Phase 2 trial (NCT02941822) to test ambroxol in Parkinson’s patients at a single center, evaluating its safety, tolerability and pharmacodynamics (how the body affects a medicine) in people with and without GBA mutations.

Twenty-four patients, all with moderate, idiopathic Parkinson’s and on “dopaminergic therapy” were enrolled in the study; 17 completed the six months of treatment and required tests. Most withdrew due to discomfort or complications with the lumbar puncture used to collect cerebral spinal fluid (CSF).

These 17 people — eight with GBA mutations and nine without GBA mutations; average age of 60 — were given a daily dose of oral ambroxol that gradually escalated from 120 mg (60 mg three times a day) to 1.26 grams (420 mg three times a day).

Clinical examination and blood testing were performed on day 11, and at three months, six months and nine months after starting the treatment. Cerebrospinal fluid samples were collected via lumbar puncture at the study’s beginning and end. Five patients also underwent a third puncture for spinal fluid collection nine months after treatment initiation.

The study’s primary goal, in addition to safety, was to assess ambroxol’s ability to cross the blood-brain barrier and to change beta-glucocerebrosidase’s activity in the brain. This was determined by measuring beta-glucocerebrosidase and ambroxol levels in patients’ blood and CSF after six months of treatment.

A significant increase of 156-ng/mL in ambroxol levels in the cerebral spinal fluid was seen at this point, indicating the therapy could cross the brain-blood barrier to reach the central nervous system. Its use was also found to be well-tolerated, without any serious side effects reported.

“This finding is important, as the administered dose was approximately 10 times higher and was administered for a longer duration than specified in its license,” the researchers wrote.

People with Parkinson’s are known to have lower levels of alpha-synuclein in their CSF than others. This may be the result of compensatory mechanisms that cells use to sequester toxic soluble alpha-synuclein, studies suggest.

After six months of ambroxol’s use, the concentration of alpha-synuclein in patients’ cerebral spinal fluid rose by 13% (an increase of 50 pg/mL) and beta-glucocerebrosidase protein levels in the CSF by 35% (an increase of 88 ng/mol). These changes underscored the therapy’s neuroprotective effect, the researchers wrote.

“The increase in total CSF [alpha]-synuclein concentration implies, based on previous in vitro and in vivo data, that ambroxol has also had an association with [alpha]-synuclein metabolism,” they said.

Compared to the beginning of the study and in line with previous research, the increase in alpha-synuclein was accompanied by a 19% decrease in beta-glucocerebrosidase’s enzymatic activity.

Ambroxol’s use also did not “aggravate motor symptoms,” the study reported, and may have helped to ease them in all treated patients (those with and without GBA mutations).

These results suggest that ambroxol can cross the blood-brain barrier and increase beta-glucocerebrosidase levels in tissues, meaning the enzyme may be able to counter the abnormal build-up of alpha-synuclein in the brain of  people with Parkinson’s, stopping or slowing it from becoming toxic to brain cells.

“Placebo-controlled clinical trials are needed to examine whether ambroxol therapy is associated with changes in the natural progression of PD [Parkinson’s disease],” the team concluded.

The Cure Parkinson’s Trust also reported on this study and its findings on its website.

“By using a drug which has shown to reduce the build-up of alpha-synuclein, and which also has a long and well-understood safety record, it is hoped that we might have a candidate for long term use that will reduce or even halt the progression of the disease,” the Trust wrote.

Larger trials are necessary, the U.K. group wrote.

“As Ambroxol is already approved as a drug … if a larger trial is successful, this drug would be readily accessible and could be seen as a treatment to slow down Parkinson’s within a short time-frame. This would have a huge impact on the lives of many people living with Parkinson’s today.”

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Baicalin Protected Rats Against Parkinson’s Neurodegeneration

baicalin study

A bioactive agent called baicalin prevented neurodegeneration of Parkinson’s disease in rats by protecting against oxidative stress and neuronal death, according to a recent study.

The results, “Neuroprotective effect and mechanism of baicalin on Parkinson’s disease model induced by 6-OHDA,” were published recently in the journal Neuropsychiatric Disease and Treatment.

Although Parkinson’s trigger is unknown, research indicates its causative mechanism involves genetics, malfunction of mitochondria (the cells’ “powerhouses”), and oxidative stress — an imbalance between the production of harmful free radicals and the ability of cells to detoxify them, resulting in cellular damage.

Taken together, these molecular and cellular changes eventually result in the death of dopamine-producing neurons, the nerve cell type that is gradually lost in Parkinson’s disease.

Available treatments only ease disease symptoms, and there are currently no disease-modifying therapies that can delay or prevent Parkinson’s neurodegeneration.

Baicalin, a compound isolated from the Chinese skullcap‘s (Labiatae Scutellaria Linn Scutellaria baicalensis Georgi) dry roots, has been shown to have antibacterial, antiviral, anti-inflammatory, anti-tumor, cardiovascular, and neuroprotective activities.

Importantly, evidence shows that baicalin protects against dopaminergic neuronal damage induced by either rotenone or MPTP, two neurotoxins that are commonly used to replicate Parkinson’s in animal models.

A Chinese team of researchers now investigated the effects of baicalin on a 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson’s disease. Like rotenone and MPTP, 6-OHDA induces the death of dopamine-producing neurons and mimics Parkinson’s symptoms.

Baicalin was given in one of three doses: low (50 mg/kg), medium (100 mg/kg), or high (150 mg/kg). Following baicalin continuous administration for eight weeks, scientists assessed animals’ fatigue, motor coordination, voluntary movement, anxiety and exploratory behavior on a weekly basis. Neuronal changes following baicalin treatment also were evaluated.

Baicalin was found to improve rats’ coordination and voluntary movement. The compound also prevented oxidative stress-related neuronal damage and death, and promoted the release of neurotransmitters to regulate dopamine-dependent communication within the rats’ brain by regulating six small metabolic molecules: N-acetyl-aspartate (NAA), aspartate, glutamate, gamma-aminobutyric acid, glycine, and taurine.

“NAA is a hallmark of neuronal changes in the brain, and a decreased level suggests a loss or dysfunction of neurons,” researchers noted. On the other hand, glutamate is mainly involved in signal transmission, and learning and memory formation.

Further analysis revealed rats with Parkinson’s had low levels of N-acetyl-aspartate (NAA) and high levels of glutamate in the striatum (a brain region involved in motor control). After continuous administration of baicalin for two months, NAA and glutamate concentrations in the striatum changed in a dose-dependent manner to almost similar levels of those seen in healthy animals: higher baicalin doses resulted in increased metabolite concentrations.

Importantly, the team believes that both NAA and glutamate levels could be potential diagnostic biomarkers to assess neurodegeneration in the context of Parkinson’s disease.

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Cannabinoid-based Possible Treatment for Parkinson’s, EHP-102, Seen as Superior to New Molecules in Early Test

cannabis as medicine

Emerald Health Pharmaceuticals announced that two of its cannabinoid-derived candidates — CBGA-Q and CBGA-Q-Na Salt — showed anti-inflammatory and neuroprotective effects in a mouse model of Parkinson’s disease. However, these benefits were not superior to those obtained from treatment with the company’s already patented EHP-102 compound.

The findings, “Comparison of the neuroprotective activity of cannabigerol derivatives in Huntington’s and Parkinson’s disease models,” were presented during the 29th Annual Symposium of the International Cannabinoid Research Society (ICRS) in Bethesda, Maryland.

Cannabinoids and other players of the endogenous cannabinoid system — a widespread neuromodulatory network involved in central nervous system development and in response to in-body and environmental stimuli — are known to exert neuroprotective effects, and have been investigated in a variety of conditions that including brain trauma, spinal injury, Alzheimer’s, Parkinson’s, and Huntington’s.

EHP-102, a compound derived from the non-psychotrophic cannabinoid called cannabigerol (CBG), has previously been shown to attenuate inflammation and neuronal loss in mouse models of Parkinson’s and Huntington’s disease.

CBGA-Q and CBGA-Q-Na Salt are two new molecules derived from cannabigerol acid being developed as possible treatments of Parkinson’s and Huntington’s.

To test these new compounds, researchers compared their activity with that of EHP-102.

When orally administered to a mouse model of Huntington’s disease, EHP-102, CBGA-Q and CBGA-Q-Na Salt all had anti-inflammatory and neuroprotective effects. But animals treated with EHP-102 showed significantly better responses in comparison to those given either CBGA-Q or CBGA-Q-Na Salt.

Oral EHP-102 and CBGA-Q also eased Parkinson’s-related behavioral symptoms and prevented neuronal loss in mice injected with 6-hydroxydopamine (6-OHDA). 6-OHDA causes cellular dysfunction and the death of dopaminergic neurons, enabling the molecular replication of Parkinson’s disease in a laboratory setting. Comparing both molecules, EHP-102 was once again found to be superior in its effects than CBGA-Q.

“Patients with Huntington’s disease and Parkinson’s disease suffer from devastating physical and psychological symptoms,” Jim DeMesa, MD, CEO of Emerald Health Pharmaceuticals, said in a news release.

“There is currently no cure for these diseases and so the results of the studies conducted by our scientific team and collaborators, which demonstrate the possible disease-modifying potential of EHP-102 and some of our other CBG-derivatives, are very encouraging.”

Given EHP-102’s “therapeutic superiority,” its developer plans to soon start the preclinical studies required to advance the compound toward clinical testing in both Parkinson’s and Huntington’s.

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Neuroprotective Mechanisms of Anavex 2-73 Revealed in Preclinical Study

Anavex 2-73 worm study

New preclinical data have shown for the first time the underlying mechanisms mediating the therapeutic activity of Anavex 2-73, an investigational therapy being evaluated for the treatment of neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS).

Anavex Life Sciences’ investigational activator of the sigma-1 receptor was found to exert its neuroprotective effect by re-establishing the normal functioning of cells’ “recycling system,” preventing the accumulation of toxic protein clumps.

The therapy is currently being evaluated in a Phase 2 clinical trial (NCT03774459) as a treatment for Parkinson’s dementia. The study, being conducted in Spain, is still recruiting participants.

The study, “Sigma-1 Receptor Activation Induces Autophagy and Increases Proteostasis Capacity In Vitro and In Vivo,” was published in the journal Cells.

Anavex 2-73 is an orally available small molecule that activates the sigma-1 receptor located in a cellular structure called the endoplasmic reticulum, which is critical for several cellular regulatory mechanisms. Activation of the sigma-1 receptor can help reduce neuroinflammation, as well as the accumulation of beta-amyloid and tau proteins, and oxidative stress, all features known to contribute to the progression of neurodegenerative disorders.

Studies in mouse models of Parkinson’s have shown that Anavex 2-73 may represent a potential strategy to treat this disease, as the compound was able to restore the function of damaged nerve cells and significantly improve motor function in these mice.

Now, using cells and worm experimental models, researchers at the medical center of the Johannes Gutenberg University in Germany have explored the underlying mechanisms involved in these therapeutic effects.

“The ability to identify key molecular functions in age-related disease is central to developing new therapeutic strategies that target these mechanisms and ultimately provide clinical impact by preventing or treating disease,” Christopher U. Missling, PhD, president and CEO of Anavex, said in a press release.

The team found that activation of the sigma-1 receptor through treatment with Anavex 2-73 could significantly improve cells’ natural recycling system called autophagy. The treatment not only enhanced the autophagic flux, it also triggered several signals involved in this process. These findings demonstrated that sigma-1 receptor activation “has a positive modulatory effect on autophagy,” according to the researchers.

Experiments with worms that had enhanced accumulation of amyloid proteins confirmed that treatment with Anavex 2-73 could effectively increase the autophagic flux by 2.5 times. Interestingly, this effect in autophagy was accompanied by a significant reduction in protein aggregates.

Deposition of amyloid proteins over time in worm’s muscle cells is known to cause paralysis. Treatment with Anavex 2-73 was able to not only prevent the accumulation of amyloid protein aggregates, but also significantly reduce the paralysis rate.

Supported by these findings, the researchers believe that induction of autophagy through Anavex 2-73 can promote proteostasis (protein rebalance) and support the clearance of toxic protein aggregates.

These results “[suggest] a possible role of sigma-1 receptor activation in the prevention (and treatment) of neurodegeneration associated with an imbalanced protein homeostasis,” the researchers wrote.

Anavex is also exploring the safety and therapeutic activity of Anavex 2-73 in a Phase 2/3 study (NCT03790709) in patients with early Alzheimer’s disease, and is preparing to launch a Phase 2 trial (NCT03758924) of Anavex 2-73 in patients with Rett syndrome.

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Investigational Herbal Therapy DA-9805 Shows Neuroprotective Effects in Parkinson’s Mouse Model

DA-9805 herbal treatment

An investigational herbal product called DA-9805 exerts its neuroprotective activity by preventing mitochondria damage in brain cells, a mouse study has found.

This compound is currently being evaluated in a Phase 2a clinical trial (NCT03189563) in early Parkinson’s disease patients.

The study, “Triple herbal extract DA-9805 exerts a neuroprotective effect via amelioration of mitochondrial damage in experimental models of Parkinson’s disease,” appeared in the journal Scientific Reports.

DA-9805 is an investigational compound being developed by the South Korean company Dong-A ST. It combines natural compounds extracted from three plants widely used in traditional Asian medicine: Moutan cortex, Angelica Dahurica root, and Bupleurum root.

Each of these plants is rich in compounds with broad therapeutic activities, including anti-inflammatory, antioxidant, anti-cancer, and analgesic proprieties.

Supported by their long history of use in traditional medicine for diseases caused by oxidative stress and inflammation, researchers hypothesized that they may also have the potential to treat Parkinson’s disease.

DA-9805 was obtained by extracting the main natural compounds of the three dried plants with 90% ethanol for 24 hours. A detailed analysis of the extracted compounds revealed the mixture was enriched for the active molecules paeonol, saikosaponin A, and imperatorin.

To evaluate the potential of the mixture, researchers exposed a cell line model often used to study Parkinson’s disease to increasing doses of DA-9805 or other reference compounds.

The treatment significantly prevented cell death induced by impaired activity of mitochondria — small cellular organelles that provide energy and are known as the “powerhouses” of cells — compared with the other tested compounds. The neuroprotective effect of DA-9805 was further confirmed when tested in cells collected from the superficial brain layer of rats.

Next, the team evaluated the effects of oral DA-9805 in a mouse model of Parkinson’s disease. This model was achieved by injecting animals with a neurotoxin called MPTP and its active metabolite MPP+, both of which exert neurotoxic effects on dopaminergic neurons — those that are mainly affected in Parkinson’s disease.

They found that treatment with DA-9805 effectively improved animals’ balance (bradykinesia) compared with placebo-treated mice. This positive effect on balance was similar to that observed in mice treated with approved Parkinson’s therapy Azilect (rasagiline).

Evaluation of dopamine levels in the striatum — the brain area most affected by the disease — showed that DA-9805, similar to Azilect, could also prevent dopamine reduction in the brain associated with Parkinson’s disease in these mice.

Importantly, although both compounds protected striatum dopaminergic neurons from death upon exposure to MPTP, DA-9805 showed a greater neuroprotective effect than Azilect.

These findings “suggest that DA-9805 has neuroprotective effects” in mice with Parkinson’s disease, according to the researchers.

Additional experiments revealed that DA-9805’s therapeutic effects were mediated by enhanced protection of mitochondria and their function, while reducing the levels of damaging oxidative molecules, also known as reactive oxygen species (ROS).

Oxidative stress is an imbalance between the production of free radicals and the ability of cells to detoxify them. These free radicals, or ROS, are harmful to the cells and are associated with a number of diseases, including Parkinson’s.

“Given that mitochondria are involved in the pathogenesis of neurodegenerative diseases, we propose that DA-9805 may be a suitable candidate for disease-modifying therapeutics against Parkinson’s disease,” the researchers wrote.

DA-9805 is now being evaluated in a Phase 2a trial in patients with early Parkinson’s disease at the HealthPartners Institute in Minnesota.

Currently recruiting participants, the randomized, double-blind study is expected to enroll about 60 patients between the ages of 30 and 79 who have had mild to moderate Parkinson’s for two years or less.

Participants will be randomly assigned to receive a daily 45 or 90 mg dose of DA-9805, or a placebo for 12 weeks. Researchers will evaluate the safety and tolerability of the treatment, as well as its ability to improve patients’ motor function.

The study is expected to be completed by March 2019.

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Protein Called Scarlet Seen to Protect Dopamine-producing Brain Cells in Early Study

Scarlet protein and dopamine

A protein called scarlet can protect nerve cells from the damaging effects of toxic alpha-synuclein aggregates that occur in Parkinson’s disease, according to results of research into a fruit fly model.

The study, “Neurodegeneration and locomotor dysfunction in Drosophila scarlet mutants,” was published in the Journal of Cell Science.

Fruit flies (Drosophila melanogaster) have proven to be useful models to study Parkinson’s disease. Similar to what happens in humans, progressive loss of dopamine-producing brain cells leads to defects in locomotor function and control.

Lehigh University researchers, along with collaborators at University of Wisconsin-Madison, evaluated the role of a protein called scarlet in a fruit fly model of Parkinson’s disease.

Upon screening a collection of fruit flies that showed degeneration of dopaminergic nerve cells, the team found some with mutations affecting the scarlet gene.

A detailed evaluation showed no significant differences in the number of dopaminergic neurons in the mutant flies compared to wild-type controls on day three. But, by day 18, the mutant flies had evident neurodegenerative onset, and by day 21 they had significantly lower numbers of neurons.

“These results demonstrate that loss of scarlet function is sufficient to promote degeneration of dopaminergic neurons,” the researchers wrote.

Scarlet mutant flies also had a shorter lifespan, with a median survival of 27 days compared to about 40 days in control flies. And these animals also impaired locomotor activity, with substantially climbing ability by day 11 and that continued to show decline by day 18.

To further explore the gene’s role, researchers induced the production of a normal scarlet gene in dopaminergic nerve cells of flies that carried its mutated version.

Using this approach, they were able to prevent neurodegeneration and rescue the progressive climbing defects previously observed. However, the flies’ lifespan was not expanded, which suggests that “Scarlet’s role in longevity requires more than [its presence] in dopaminergic neurons,” the researchers wrote.

Additional analysis revealed that flies that lacked scarlet had higher levels of potentially damaging reactive oxygen elements, also known as ROS. In contrast, flies that had been genetically altered — given a healthy working version of the scarlet gene — had lower ROS levels in the brain.

“Because dopaminergic neurons are particularly vulnerable to oxidative stress,” these findings suggest that scarlet’s role in Parkinson’s could in part be to limiting oxidative stress, the researchers wrote.

Oxidative stress is an imbalance between the production of free radicals and the ability of cells to detoxify them. These free radicals, or ROS, are harmful to cells and  associated with a number of diseases, including Parkinson’s.

Researchers also explored the role of the scarlet protein in flies that had been genetically engineered to carry the human alpha-synuclein protein in dopaminergic neurons.

In the presence of alpha-synuclein — either the normal version or two mutated forms linked to familial Parkinson’s disease — flies experienced significant loss of dopamine-producing cells.  But scarlet was present, even together with alpha-synuclein, the loss of dopamine-producing cells was prevented.

“The experiment demonstrated that Scarlet was sufficient in preventing dopaminergic neuron loss, suggesting a neuroprotective function,” Patrick Cunningham, a PhD student at Lehigh University and study author, said in a Journal of Cell Science interview.

“We found that the fruit fly mutant scarlet [gene], commonly associated with a bright red eye color, showed progressive DA [dopaminergic] neuron loss that was accompanied by impaired movement coordination,” Cunningham added. “A mutation causes errors in the protein that is associated with a specific gene; in other words, the scarlet mutant has a dysfunctional Scarlet protein.”

When the protein was added to mutant flies, it’s presence “showed a neuroprotective function by preventing the loss of DA neurons and maintaining movement coordination.”

The presence of scarlet protein, indeed, helped to ease difficulties with motor function — as seen in the climbing problems — that were induced by all three forms of alpha-synuclein.

“The identification of a neuroprotective role for Scarlet should help in characterizing the selective vulnerability of dopaminergic neurons in Parkinson’s disease,” the researchers wrote.

“Thus, investigating mechanisms uncovered here should be helpful for uncovering potential therapeutic targets to prevent the loss of these neurons,” they concluded.

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Engineered Protein May Lead to New Parkinson’s Therapy, Preclinical Study Suggests

Nurr1 protein

A modified form of a protein called Nurr1 that is able to protect against nerve cell death and restore dopamine production in a preclinical setting may pave the way for a possible new Parkinson’s therapy, a study reports.

The study, “Lethal Factor Domain-Mediated Delivery of Nurr1 Transcription Factor Enhances Tyrosine Hydroxylase Activity and Protects from Neurotoxin-Induced Degeneration of Dopaminergic Cells,” was published in the journal Molecular Neurobiology.

The nuclear receptor-related 1 protein, or Nurr1, plays a role in the development and survival of dopamine-producing neurons in the brain, a cell population that progressively degenerates in Parkinson’s disease, leading to lower dopamine levels.

As a type of protein called a transcription factor, Nurr1 controls the production of other key proteins in these neurons, while also regulating apoptosis, or “programmed” cell death.

An age-dependent reduction in Nurr1 levels has been proposed as one of the causes behind the loss of dopamine-producing neurons in Parkinson’s patients. Preclinical work showed that elevated levels of this protein provide anti-inflammatory benefits and neuroprotection.

Gene therapy approaches to deliver Nurr1 into animals and administration of compounds designed to boost its effects have shown promising results, but the protein’s inability to enter cells and reach their nucleus has remained a limitation for the potential development of therapies.

But now researchers from Ruhr Universitat Bochum in Germany and the U.S. National Institute of Allergy and Infectious Diseases at the National Institutes of Health have found a way to modify Nurr1 with a nontoxic bacterial protein fragment, a similar mechanism by which Bacillus anthracis infiltrates animal cells and causes anthrax, to help it get where it needs to go. A protein known as SUMO was also used to increase Nurr1’s stability.

“The fragment of bacterial protein that we used does not trigger diseases; it merely contains the command to transport something into the cell,” Rolf Heuman, one of the study’s authors, said in a press release.

After it is taken up by the cell, the protein fragment is detached, and Nurr1 is then able to reach its target genes by using the cell’s own nuclear import machinery.

Using human dopamine-producing cells grown in the laboratory, researchers found that successful delivery of modified Nurr1 was associated with higher levels of an enzyme called tyrosine hydroxylase, the key enzyme in dopamine production.

The team also tested the effect of modified Nurr1 on the cultured cells treated with the neurotoxin 6-hydroxydopamine, which causes the dopamine-producing cells to die and is used as a model for Parkinson’s. Nurr1 was able to inhibit the neurotoxin-induced degeneration of cells.

“Nurr1 fusion protein may contribute to the development of a novel concept of protein-based therapy,” the researchers wrote in the study.

Current Parkinson’s medications are not able to restore dopamine-producing neurons or stop their degeneration. A different approach, deep brain stimulation, has been effective in easing motor symptoms, but still carries safety risks.

“We hope we can thus pave the way for new Parkinson’s therapy,” said Sebastian Neumann, the study’s senior author. “Many steps still remain to be taken in order to clarify if the modified protein specifically reaches the right cells in the brain and how it could be applied.”

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Source: Parkinson's News Today

Emerald Health Pharmaceuticals’ Cannabinoid-Derived Compound Beneficial in Parkinson’s, Mouse Study Finds


Emerald Health Pharmaceuticals investigational EHP-102 (previously known as VCE-003.2), a patented compound derived from the non-psychotrophic cannabinoid called cannabigerol, has shown anti-inflammatory and neuroprotective properties in a mouse model of Parkinson’s disease.

The study “Benefits of VCE-003.2, a cannabigerol quinone derivative, against inflammation-driven neuronal deterioration in experimental Parkinson’s disease: possible involvement of different binding sites at the PPARγ receptor” was published in the Journal of Neuroinflammation.

Cannabinoids are the active chemicals that give the cannabis plant its medical and recreational properties. Researchers evaluated the anti-inflammatory and neuroprotective properties of EHP-102 in cellular models of neuroinflammation and in mice that, after injection of a specific molecule (LPS) directly into a brain region called corpus striatum, developed the inflammatory symptoms characteristic of Parkinson’s disease.

LPS induces the reactivation of microglia cells and increases the expression of proinflammatory markers in the brain striatum, including iNOS, which has been found to contribute to the loss of neurons observed in Parkinson’s disease.

Mice treated with the cannabinoid EHP-102 showed a reduction in the reactivation of microglia cells in the brain, accompanied by a marked reduction in the levels of pro-inflammatory markers, attenuating the loss of neurons.

Importantly, EHP-102 also was efficient in attenuating inflammation in mouse and rat microglia cell lines treated with LPS.

Researchers confirmed that the therapeutic activity of EHP-102 is not mediated by its effects on the cannabinoid receptors, but rather via activation of a different type of receptor that belongs to the peroxisome proliferator-activated receptor (PPAR) family.

“More than 10 million people worldwide are living with Parkinson’s disease and many do not have access to effective therapies to treat symptoms of the disease,” Eduardo Muñoz, PhD, said in a press release. Muñoz is EHP’s chief scientific officer and professor of immunology at the University of Córdoba,

“We believe these findings will help advance preclinical studies and clinical trials of cannabinoid-derived medicines and add to the experimental evidence that shows this pharmaceutical agent may preserve neuronal integrity in Parkinson’s disease,” he added.

“We congratulate Drs. Muñoz and Bellido [Mari-Luz Bellido, PhD, EHP’s vice president of European Operations] for their publication in a prominent scientific journal,” said Jim DeMesa, MD, CEO of Emerald Health Pharmaceuticals. “These outstanding scientists have been pioneers in cannabinoid science for over fifteen years and we are proud to be working closely with them as we develop our two novel cannabinoid drugs targeting life-threatening neurodegenerative and auto-immune diseases.”

This team has shown previously that many of its patented cannabidiol and cannabigerol derivatives also affect other disease-modifying targets, and is currently developing two drug candidates from its portfolio of cannabinoid analogs, one derived from cannabidiol for multiple sclerosis and scleroderma.

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Source: Parkinson's News Today