Posts

Anavex 2-73 Trial Recruitment Reaches Halfway Mark

Anavex 2-73

A Phase 2 trial evaluating the efficacy and safety of investigational Anavex 2-73 as a treatment for Parkinson’s disease dementia has recruited half of its targeted patients, the therapy’s developer, Anavex Life Sciences, has announced.

The study is still recruiting Parkinson’s disease patients age 50 or older who have been diagnosed with dementia. The Phase 2 trial is being conducted across several clinical sites in Spain, and has received the support of the Michael J. Fox Foundation for Parkinson’s Research and León Research.

“We are encouraged by the rate of patient enrollment in this Phase 2 study and the potential for Anavex 2-73 to become a therapy for this unmet need given that up to 80% of Parkinson’s patients develop dementia,” Christopher U. Missling, PhD, president and chief executive officer of Anavex, said in a press release.

The Phase 2 trial (2017-004335-36expects to enroll 120 patients who will be randomized to receive orally 10 or 20 mg of Anavex 2-73 or a placebo for 14 weeks. Researchers will evaluate the impact of the treatment on cognition, as determined by the cognitive drug research computerized assessment system, as well as patients’ motor function and sleep quality.

The study will also assess genomic precision medicine biomarkers, previously identified to respond to Anavex 2-73 in a Phase 2 trial (NCT02244541) in Alzheimer’s disease.

Anavex 2-73, originally developed as a potential disease-modifying therapy for Alzheimer’s, is given orally to activate a cellular receptor called Sigma-1 (SIGMAR1), known to have neuroprotective effects. Specifically, activation of SIGMAR1 can help reduce neuroinflammation, as well as the accumulation of beta-amyloid and tau proteins and oxidative stress, all known to contribute to the progression of neurodegenerative disorders.

According to a recent study published in the journal Cells, the therapy exerts its neuroprotective effects by re-establishing the normal functioning of cells’ “recycling system,” preventing the accumulation of toxic protein clumps.

Preclinical studies with mouse models of Parkinson’s disease have shown that Anavex 2-73 was able to restore the function of damaged nerve cells and significantly improve motor function.

Currently, only one medicine, Nuplazid (pimavanserin) is approved by the the U.S. Food and Drug Administration (FDA) as a therapy for hallucinations and delusions associated with Parkinson’s disease.

The post Anavex 2-73 Trial Recruitment Reaches Halfway Mark appeared first on Parkinson’s News Today.

Cognitive Performance in Parkinson’s Linked to Sleep Efficiency, Study Shows

sleep study

University of São Paulo researchers have found that Parkinson’s patients with dementia sleep less and less efficiently, which affects their overall cognitive performance.

The study with that finding, “Global cognitive performance is associated with sleep efficiency measured by polysomnography in patients with Parkinson’s disease,” was published in Psychiatry and Clinical Neurosciences.

Non-motor complications associated with Parkinson’s disease, including cognitive impairment and sleep disturbances, can drastically affect patients’ quality of life.

Evidence suggests an interaction between sleep disorders and cognition. For instance, sleep after learning helps memory consolidation.

In addition, people with obstructive sleep apnea syndrome or chronic insomnia have cognitive abnormalities, which could be reversed after proper treatment of the underlying sleep disturbance.

Although there is still no consensus about whether sleep disorders are associated with cognitive dysfunction, studies suggest an association and add that rapid eye movement (REM) sleep behavioral disorder may be associated with increased risk for cognitive decline. REM is a sleep stage in which the eyes move rapidly in various directions.  During sleep, the body cycles between intervals of basic states: REM sleep and non-REM sleep.

Researchers in Brazil now examined a possible association between clinical variables, cognitive status and the presence of sleep abnormalities and symptoms in Parkinson’s patients.

Investigators performed detailed clinical and cognitive assessment in 79 patients. Participants were mostly men (61%), 51-72 years old, and a disease duration varying between 3.9 and 13.9 years.

Based on cognitive diagnosis, researchers categorized patients as those with normal cognition (29 patients), mild cognitive impairment (39 patients) or dementia (11 patients).

Within two weeks after initial medical evaluation, participants were submitted to an overnight polysomnography, meaning they had their brain waves, blood oxygen level, heart rate, breathing patterns, and eye and leg movements monitored while they were asleep.

Compared to Parkinson’s patients with normal cognition, the dementia group was older, had more severe disease, and more difficulty performing daily activities. Dementia patients also took higher daily levodopa-equivalent dose than participants without abnormalities.

Patients with dementia had lower sleep efficiency, less total sleep time and lower number of sleep state changes, in comparison to the normal cognition group.

Researchers also found an association between sleepiness, measures of obstructive sleep apnea and sleep symptoms, which were assessed by the Parkinson’s Disease Sleep Scale and the Pittsburgh Sleep Quality Index.

“Concerning sleep disorders and sleep symptoms, [there was] no significant differences between groups in the proportion of cases with obstructive sleep apnea, chronic insomnia, [REM sleep behavioral disorder] and [restless legs syndrome]. We also did not observe significant differences between scores of patients in the three groups about excessive daytime sleepiness, quality of sleep and general sleep-related symptoms. There was also no significant differences in the number of sleep disorders between the groups,” authors wrote.

There was a significant association between overall (aka “global”) cognitive performance and wakefulness and the number of sleep state changes during sleep.

“However, we did not find any other association between sleep disorders or symptoms and cognitive status or cognitive performance of patients with Parkinson’s,” researchers wrote.

The team believes the association with the number of state changes during sleep may be because Parkinson’s disease patients with dementia slept less than the other subsets and as such, had less time to change between sleep states.

“We hope that, in the near future, new prospective controlled studies, with more significant numbers of patients, could evaluate, in detail, the relationship of different variables related to sleep with cognitive functions in this specific population,” researchers concluded.

The post Cognitive Performance in Parkinson’s Linked to Sleep Efficiency, Study Shows appeared first on Parkinson’s News Today.

Phase 2 Trial Testing Anavex 2-73 Recruiting Parkinson’s Patients With Dementia in Spain

Anavex 2-73 enrolling trial

The first patient has been enrolled in Anavex Life Sciences‘ Phase 2 clinical trial to evaluate the potential and safety of Anavex 2-73 as a treatment for Parkinson’s disease dementia.

Now actively recruiting, the study (2017-004335-36) is expected to enroll approximately 120 Parkinson’s patients ages 50 or older with a dementia diagnosis. It is being conducted across several clinical sites in Spain, and has received the support of the Michael J. Fox Foundation for Parkinson’s Research and León Research.

Anavex has been developing Anavex 2-73 as a potential disease-modifying therapy for Alzheimer’s disease. It is a 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.

“We are very pleased to initiate our first patient enrollment into the Parkinson’s disease dementia Phase 2 study of Anavex 2-73,” Christopher U. Missling, PhD, president and CEO of Anavex, said in a press release. “This is an important step toward achieving clinical data for the second indication initiating this year for Anavex 2-73 also incorporating genomic precision medicine biomarkers.”

Trial participants will be randomly assigned to receive orally 10 or 20 mg of Anavex 2-73 or a placebo for 14 weeks.

Researchers will evaluate the impact of the treatment on cognition, as determined by the cognitive drug research computerized assessment system, as well as on patients’ motor function and sleep quality.

During the study, researchers will also assess genomic precision medicine biomarkers associated with Anavex 2-73 that were identified in another Phase 2 trial (NCT02244541) in Alzheimer’s disease.

Additional information (in Spanish) on the trial can be found here. Patients and caregivers interested in taking part in the study can download and fill out a simple screening questionnaire that is available on the website to assist in discussions with their physician.

“Parkinson’s disease is an already prevalent disease among older individuals that is poised to become a much greater public health problem around the globe in the coming decades and is now appreciated commonly to cause cognitive impairment, including dementia, and behavioral changes,” Jaime Kulisevsky, MD, PhD, principle investigator of the Phase 2 trial, as well as a professor at the Autonomous University of Barcelona and director of the Movement Disorders Unit of the Sant Pau Hospital in Barcelona.

Results from preclinical studies have shown that Anavex 2-73 has the potential to restore function to damaged nerve cells in mouse models of Parkinson’s disease. The compound was also found to target faulty proteins and poorly working mitochondria — the cells’ powerhouses — preventing oxidative stress and inflammation.

As of now, only one medication, Nuplazid (pimavanserin) is approved by the U.S. Food and Drug Administration for the treatment of hallucinations and delusions associated with Parkinson’s disease.

The post Phase 2 Trial Testing Anavex 2-73 Recruiting Parkinson’s Patients With Dementia in Spain appeared first on Parkinson’s News Today.

Tiny Brain Bleeds Associated with Parkinson’s Disease Dementia, Study Reports

cerebral microbleeds, dementia

Tiny bleeds in the brain are associated with cognitive impairment in Parkinson’s disease and risk of Parkinson’s disease dementia (PDD), a Japanese study has found.

The research, “The presence of cerebral microbleeds is associated with cognitive impairment in Parkinson’s disease,” was published in the Journal of Neurological Sciences.

Cerebral microbleeds (CBMs) are small, chronic brain hemorrhages likely caused by structural abnormalities of the small vessels in the brain. CBMs are markers of small vessel disease frequently found in normal aging, as well as in patients with stroke and Alzheimer’s disease. These lesions are known promoters of cognitive decline in the elderly and are linked to poor prognosis in Alzheimer’s patients.

Cognitive impairment is one of Parkinson’s non-motor symptoms and, along with dementia, affects Parkinson’s prognosis. Other non-motor symptoms – including visual hallucinations, sleep problems, behavior disorders, and orthostatic hypotension (a decrease in blood pressure when standing up), as well as older age at onset — are considered risk factors for Parkinson’s cognitive decline.

The authors previously had shown that CBMs are common in Parkinson’s patients. Also, experimental studies reported that brief brain blood flow reduction promotes the aggregation of alpha-synuclein protein, a key player in Parkinson’s disease.

However, whether the presence of these lesions is a risk factor for cognitive impairment in patients with Parkinson’s was not clear.

Juntendo University researchers retrospectively analyzed a total of 124 clinically diagnosed Parkinson’s patients to determine the association between the presence of CBMs and cognitive decline. Both early-stage and advanced disease cases were included.

Twenty-one patients (16.9%) were diagnosed with PDD. Factors including gender, age, Hoehn and Yahr (H-Y) stage (a system used to assess the worsening of Parkinson’s symptoms) history of stroke, orthostatic hypotension (defined as a 20-mm Hg drop in systolic and/or a 10 mm Hg drop in diastolic blood pressure), systolic hypertension (systolic blood pressure equal to or higher than 140 mm Hg), specific cerebrovascular lesions, and the use of oral blood thinners. All significantly correlated with PDD.

Matching prior findings, abnormal nocturnal blood pressure — increasing or falling 10 to 20% — also was associated with PDD.

CBMs — defined by brain MRI as having a diameter of 2-10 mm — were observed more frequently in PDD patients than in those without dementia. This finding was maintained across different microbleeds’ types called deep or infratentorial (below the brain lobes) and strictly lobar (restricted to the brain lobes).

Also, both types of CBMs were associated with lower cognitive scores, as measured with the Mini-Mental State Examination (MMSE) and the Hasegawa dementia scale-revised. Patients with a strictly lobar type of microbleed scored lower on both scales than individuals with deep or infratentorial ones.

Patients with CBMs were older and had a higher (worse) H-Y stage than those without these lesions. They also showed more severe cerebrovascular lesions and higher prevalence of hypertension, diabetes mellitus, history of ischemic stroke, coronary artery disease, orthostatic hypotension, systolic hypertension, and use of oral blood thinners and anti-hypertensive medications.

Importantly, male gender, cerebrovascular lesions on MRI, and strictly lobar CMBs (but not deep and infratentorial) were risk factors for PDD.

“In conclusion, CMBs, especially strictly lobar type, are associated with cognitive decline and dementia in [Parkinson’s],” researchers wrote.

Amyloid plaques — typical in Alzheimer’s patients’ brains — are known contributors for cognitive decline in Parkinson’s and are more common in PDD patients than in those with Parkinson’s but not dementia. In fact, up to 50% of patients with PDD also may have an Alzheimer’s pathology.

“[O]ur data suggest that [Parkinson’s] cases with strictly lobar distribution of CMBs may have an underlying [Alzheimer’s] pathology and contribute to cognitive decline,” the scientists added.

However, the research team noted that future studies with larger patient groups are necessary to confirm these results.

The post Tiny Brain Bleeds Associated with Parkinson’s Disease Dementia, Study Reports appeared first on Parkinson’s News Today.

Source: Parkinson's News Today

Eli Lily Recruiting for Phase 2 Trial to Test LY3154207 for Parkinson’s Dementia

LY3154207 study

Eli Lilly is recruiting patients for its Phase 2 clinical trial evaluating LY3154207 as a potential treatment for Parkinson’s disease dementia (PDD).

Parkinson’s disease destroys the nerve cells that make dopamine, a key player in nerve cell communication and involved in movement control, cognition, memory, learning, attention, and sleep.

Parkinson’s main affected brain area is the substantia nigra, which controls movement, but as the disease progresses and spreads in the brain, it can affect the areas responsible for mental functions, memory, and judgment.

About 50 percent of Parkinson’s patients will experience some form of cognitive impairment, which is diagnosed as Parkinson’s disease dementia when it affects more than one area of cognition and is severe enough to impair social or work functioning.

Symptoms of PDD can include attention difficulties, forgetfulness, and slow thought processes. This can make communication difficult, as remembering words and names and following conversations can be challenging.

Eli Lilly is developing LY3154207, an orally administered enhancer of dopamine receptor D1 — a type of dopamine receptor involved in cognition — for the treatment of PDD.

Previous preclinical studies have shown that enhancing dopamine receptor D1 can improve cognitive function, including attention.

In March 2017, a Phase 1 study (NCT02562768) evaluating LY3154207’s safety, tolerability, and how the body processes the therapy, was completed in healthy volunteers and Parkinson’s patients.

Now, a randomized placebo-controlled Phase 2 study called PRESENCE (NCT03305809) will evaluate the safety and effectiveness of three doses of LY3154207 in patients with mild-to-moderate Parkinson’s disease dementia.

Ely Lilly seeks to enroll 340 individuals, 46-85 years old, in centers from four countries: U.S., Canada, China, and Puerto Rico. Participants must have Parkinson’s disease with at least two years of symptoms, have PDD with a decline in cognitive function leading to functional impairment, have no history of a stroke in the past six months, and no signs/diagnosis of psychotic diseases.

Participants will be chosen randomly to receive daily either one of the three doses of LY3154207, or a placebo, for 12 weeks.

The study’s main goal is improvement in the ability to sustain concentration for a period of time without error —assessed through the Continuity of Attention (CoA) Composite Score of the Cognitive Drug Research Computerized Cognition Battery (CDR-CCB).

Secondary goals include improvements in cognitive function and attention, daytime sleepiness, dementia-related behavioral symptoms, activities of daily life, and motor function.

The PRESENCE study is estimated to conclude by July 2019.

The post Eli Lily Recruiting for Phase 2 Trial to Test LY3154207 for Parkinson’s Dementia appeared first on Parkinson’s News Today.

Source: Parkinson's News Today

Phase 2 Study of Potential Oral Therapy for Parkinson’s Dementia, Anavex 2-73, Planned

Anavex 2-73

Anavex Life Sciences is planning to open a Phase 2 clinical trial testing Anavex 2-73, a potential oral treatment for patients with Parkinson’s disease dementia (PDD), this year.

Anavex 2-73 aims to treat PDD by binding to the sigma-1 receptor, located in a cellular structure called the endoplasmic reticulum and important to protein production and transport.

The proposed double-blind, placebo-controlled trial will evaluate Anavex 2-73’s ability to ease both cognitive and motor difficulties in Parkinson’s patients. A trial application is before European regulators, with plans to start this study in the second half of 2018.

According to the Parkinson’s Foundation, around 50 to 80 percent of Parkinson’s patients will develop disease-related dementia. Parkinson’s is characterized by the loss of neurons in a crucial brain area that controls movement, the substantia nigra. This loss, in turn, lowers brain levels of dopamine, a key player in nerve cell or neuronal communication.

With disease progression, these changes spread to other areas of a patient’s brain, affecting memory, attention, and thinking and reasoning.

“As many as 80 percent of people with Parkinson’s will experience Parkinson’s disease dementia and treatment options are limited,” Christopher Missling, president and CEO at Anavex, said in a press release.

Results of preclinical work, fully funded by the The Michael J. Fox Foundation for Parkinson’s Research, show that treatment with Anavex 2-73 was able to restore function to damaged nerve cells in mouse models of Parkinson’s disease. Data also demonstrated that it targets misfolded proteins and poorly working mitochondria — a cell’s energy source — to prevent oxidative stress, inflammation, and cellular stress.

“We are excited to progress our program to Phase 2, with a focus on the many patients with Parkinson’s disease dementia, and we remain focused on the discovery and development of potential treatments for neurological diseases with unmet needs, including Alzheimer’s disease and Rett syndrome,” Missling added.

Anavex filed an updated investigational new drug application to the U.S. Food and Drug Administration (FDA) earlier this year for a double-blind, Phase 2 study evaluating Anavex 2-73 in Rett syndrome. If approved, this trial is also expected to open in late 2018.

The company plans to open a Phase 2/3 trial of Anavex 2-73 in up to 300 people with mild-to-moderate forms of Alzheimer’s disease.  A Phase 2a dose-escalating study (NCT02244541) involving 32 people with probable Alzheimer’s was conducted at sites across Australia.

The post Phase 2 Study of Potential Oral Therapy for Parkinson’s Dementia, Anavex 2-73, Planned appeared first on Parkinson’s News Today.

Source: Parkinson's News Today