Cancer Medication Tasigna Safely Boosts Dopamine Levels in Brain of Parkinson’s Patients, Phase 2 Trial Shows

Tasigna, Parkinson's

Tasigna (nilotinib), an approved leukemia medication being tested as a repurposed treatment for Parkinson’s disease, was found to be safe and increased the levels of dopamine in the brain of patients with Parkinson’s disease, a Phase 2 trial shows.

The findings were reported in a study, “Nilotinib Effects on Safety, Tolerability, and Potential Biomarkers in Parkinson Disease: A Phase 2 Randomized Clinical Trial,” and published in JAMA Neurology.

Tasigna, developed by Novartis, is approved by the U.S. Food and Drug Administration and the European Medicines Agency to treat adults with chronic myeloid leukemia, a type of blood cancer that typically affects older adults.

The medicine blocks the activity of a protein called BCR-ABL, which is known to support cancer development. But this protein is also intimately linked to several mechanisms in the brain, such as oxidative stress (cellular damage as a consequence of high levels of oxidant molecules) and alpha-synuclein-induced neurodegeneration, which play critical roles in Parkinson’s and other brain disorders.

For that reason, researchers wondered if Tasigna could be repurposed to treat Parkinson’s disease. Drug repurposing refers to the process of testing a medication with established safety in conditions other than those for which it was originally intended.

pilot study in 12 individuals with Parkinson’s disease dementia and dementia with Lewy bodies suggested that this therapy could effectively treat Parkinson’s motor and non-motor symptoms, while also increasing dopamine metabolism (its use in the brain) and lowering alpha‐synuclein levels.

Subsequently, researchers in the new study sought to investigate the safety, tolerability, and pharmacokinetic properties of Tasigna in a placebo-controlled, Phase 2 trial (NCT02954978) carried out at Georgetown University Medical Center (GUMC). Pharmacokinetics refers to how a drug is absorbed, distributed, metabolized, and eliminated from the body.

The study enrolled 75 patients with moderate-to-severe Parkinson’s disease who were randomly assigned to receive one of two oral doses of Tasigna (150 or 300 mg daily), or a placebo, for a period of one year, followed by a washout period of three months, in which they stopped taking the medication or the placebo.

The mean dose of levodopa at enrollment was similar between groups.

Earlier findings from the study showed that treatment with a single low dose of Tasigna improved the brain’s ability to use dopamine stored in small vesicles in specific brain regions of Parkinson’s patients by reducing inflammation and the levels of toxic alpha-synuclein.

Most of the patients enrolled (88%) completed the study. A total of nine patients withdrew from the study, including two who had been assigned to the placebo, three who had been assigned to receive the lowest dose of Tasigna, and four who had been assigned to receive the highest dose of the medication. From these, two withdrew from the study due to serious adverse events.

Tasigna was considered reasonably safe and well-tolerated, with most adverse events being mild or moderate in severity. The most common non-serious adverse events included falls, and musculoskeletal, respiratory, and skin conditions. Gastrointestinal and heart problems were less common.

In a secondary exploratory analysis of biomarkers, the investigators found that patients treated with Tasigna experienced a reduction in the levels of two toxic proteins that are considered hallmarks of Parkinson’s disease: a 20% decrease in alpha-synuclein and 30% reduction in tau.

In addition, they discovered that those taking Tasigna had an increase of more than 50% in the levels of dopamine (the brain chemical missing in those with Parkinson’s disease), suggesting that reducing the levels of toxic proteins could help the brain to use dopamine more effectively.

Those taking Tasigna performed better on motor tests and tended to have better scores in the PDQ-39 questionnaire (a measure of quality of life) compared to those treated with the placebo.

“We see that subjects on nilotinib performed better overall on motor testing and had a better quality-of-life measurement during the study than the placebo group. These are important observations suggesting that nilotinib stabilized the disease — a potential disease modifying effect that we haven’t observed with any other agents,” Fernando Pagan, MD, medical director of the GUMC Translational Neurotherapeutics Program and principal investigator of the study, said in a press release.

“These clinical findings need confirmation through larger studies with more diverse populations,” added Pagan, who also directs the Movement Disorders Clinic at MedStar Georgetown University Hospital.

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Cerevance’s Phase 2 Trial Recruiting Patients to Test Oral CVN424 Therapy for Motor Symptoms

CVN424 Phase 2 trial

Cerevance has initiated a Phase 2 clinical trial to evaluate the safety and efficacy of its oral investigational therapy CVN424 for treating Parkinson’s disease motor symptoms.

CVN424 is small molecule that can penetrate the brain and modulate the activity of specific nerve cells in the striatum region that control body movement. In contrast to available therapies, CVN424 specifically targets a non-dopaminergic protein involved in signaling pathways that can activate brain cells.

This new strategy is anticipated to induce positive therapeutic effects similar to current standard-care treatments for Parkinson’s while avoiding side effects such as dyskinesia.

“We are pleased to further advance the clinical development of CVN424 in Parkinson’s, as there remain significant shortcomings with current therapeutics,” Brad Margus, Cerevance’s CEO, said in a press release.

Preclinical studies have shown that CVN424 can improve locomotor activity in animal models of Parkinson’s disease.

Results from a previous Phase 1 study (NCT03657030) showed that CVN424 was safe and well-tolerated compared with placebo. The trial enrolled 64 healthy volunteers who received either single doses or seven daily doses of CVN424, ranging from 1 mg to 225 mg, or placebo. No serious or severe adverse events or clinically significant changes were reported or associated with the therapy.

Oral administration of CVN424 was rapidly absorbed by the body and its stability profile supported a once-daily dosing regimen as the optimal treatment approach for future studies.

These positive data supported the launch of the multicenter, placebo-controlled Phase 2 trial that will now evaluate CVN424’s efficacy and safety in Parkinson’s patients with motor fluctuations who are being treated with levodopa.

The trial is expected to enroll approximately 70 participants, ages 30 to 80, who will be randomly assigned to receive one of two doses of CVN424 or a placebo.

The researchers will evaluate CVN424’s potential for reducing “off” time — periods of the day when Parkinson’s symptoms return despite ongoing medication — as well as other functional outcome measures.

“CVN424 activates key motor pathways, but not the neurons implicated in dyskinesias, a common side effect of dopaminergic Parkinson’s disease treatments,” said David H. Margolin, MD, PhD, senior vice president of clinical and translational medicine at Cerevance. “This selectivity should allow CVN424 to augment the positive effects of the current standard of care, levodopa, without exacerbating its side effects.”

More information about the trial, including participating clinical sites and contacts, is available here.

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Phase 2 Study to Evaluate Possible Oral Treatment for Mild Cognitive Impairment in Parkinson’s

cognitive impairment study

Aptinyx will soon open a Phase 2 clinical study of NYX-458, a potential oral treatment of mild cognitive impairment (MCI) associated with Parkinson’s disease (PD).

Although the main features of Parkinson’s involve difficulties with mobility and motor function, many patients also experience non-motor symptoms that include cognitive problems, for which few options exist.

Parkinson’s is a progressive disease of the nervous system, but “more than half of all people suffering from the disease are also afflicted by cognitive symptoms,” C. Warren Olanow, MD, a professor emeritus in the Departments of Neurology and Neuroscience at the Mount Sinai School of Medicine, and a Parkinson’s expert, said in a press release.

These cognitive symptoms include impaired thought processes and memory, resulting in a form of dementia. Many researchers believe that these symptoms are caused by changes in the function of a molecule called the N-methyl-D-aspartate (NMDA) receptor.

These receptors are involved in the communication between nerve cells and help regulate synaptic plasticity, which is the ability of synapses — the junctions between two nerve cells that allow them to communicate — to form strong connections and to reduce ones that are no longer needed. In this way, we form stable memories of important events, while allowing less vital memories to fade.

NYX-458 is a small molecule compound that controls the activity of the NMDA receptor.

The Phase 2 trial (NCT04148391) is a randomized, placebo-controlled study. Its goal is to determine the safe dosing and potential cognitive benefits of NYX-458.

Up to 135 trial patients, ages 50 to 80, will receive daily oral doses of 10 mg, 30 mg, or 100 mg of the investigative medication, or a placebo capsule, over a 12-week period. NYX-458’s efficacy will be measured by how it affects patients’ memory, attention, executive function, visuospatial deficits, and quality of life.

The trial is not yet recruiting. Current enrollment information can be found here.

Addressing NMDA receptor dysfunction would mark an important therapeutic advance. “Indeed,” said Olanow, “no therapy has been approved for the treatment of MCI [mild cognitive impairment] in PD, which remains a substantial unmet need.”

Aptinyx previously reported that NYX-458 successfully reversed cognitive deficits in a non-human primate model of Parkinson’s disease. NYX-458 significantly increased attention, improved cognitive flexibility, and enhanced working memory as quickly as two hours after the administration of a single oral dose. Those effects were maintained for up to three weeks. No major safety or tolerability issues were observed.

Earlier this year, the company also reported positive Phase 1 safety results. The study included 62 healthy volunteers were given single and repeat doses of NYX-458 at multiple levels to determine the optimal dose for future Phase 2 studies.

“We are excited about the potential for NYX-458 to alleviate the cognitive impairment associated with Parkinson’s disease,” said Norbert Riedel, Ph.D., president and CEO of Aptinyx.

The company expects to report topline trial results in the second half of 2021.

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Phase 2 Trial of SEP-363856, Potential Oral Treatment of Parkinson’s Psychosis, Enrolling in US

SEP-363856 psychosis trial

A Phase 2 clinical trial of SEP-363856, an oral treatment candidate for people with Parkinson’s psychosis, is now recruiting patients across the U.S.

SEP-363856 is a candidate therapy being developed by Sunovion to treat schizophrenia, and the hallucinations and delusions linked to Parkinson’s disease. It is designed to act as an antipsychotic agent, but through a mechanism distinct from currently available antipsychotics. Specifically, it does not bind to dopamine 2 (D2) or serotonin 2A (5-HT2A) receptors, as current antipsychotics are thought to do.

The 21-week, multi-part Phase 2 SEP361-203 trial (NCT0299369) is expected to enroll up to 36 patients, ages 55 and older, at 24 sites. Among them, 24 people will initially be randomized to SEP-363856 treatment and 12 will be given a placebo.

Eligible patients must have been diagnosed at least one year before study’s start, and have been experiencing such psychosis symptoms as visual hallucinations or paranoia (delusions). Participants also need to have a caregiver able to attend an estimated 13 on-site visits.

Following an initial screening, patients will be randomly assigned to either SEP-363856 oral capsules at 25, 50, or 75 mg once daily, or to a matching placebo, for six weeks. This treatment period will be followed by 12 weeks of an open-label extension phase, during which all participants will be given SEP-363856.

Researchers will evaluate the safety, tolerability, and effectiveness of the candidate therapy.

They will assess changes in the Scale for Assessment of Positive Symptoms–Parkinson’s Disease (SAPS-PD) total score, which addresses manifestations of hallucinations and delusions. Researchers will also evaluate, as secondary trial goals, disease severity and patients’ cognitive function.

The roughly five-month study is expected to expected to conclude in May 2020.

SEP-363856 was designated a breakthrough therapy as a potential treatment of schizophrenia by the U.S. Food and Drug Administration in May, based largely on results from a Phase 2 trial and an open-label extension study. The designation offers FDA guidance to the company in developing the potential treatment, and priority review should a request be filed for approval.

Currently, Nuplazid (pimavanserin), by Acadia, is the only FDA-approved medication for treating hallucinations and delusions associated with Parkinson’s disease.

More information on the SEP361-203 study is available on its website.

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Phase 2 Clinical Trial Recruiting People with Early Parkinson’s to Explore Experimental K0706


Sun Pharma Advanced Research Company (SPARC) is conducting a Phase 2 clinical study to evaluate the safety and effectiveness of its experimental Abl inhibitor K0706 in people with early Parkinson’s disease.

The trial, which is still recruiting, is estimated to enroll approximately 504 participants, age 50 or older, who have been diagnosed with “clinically probable Parkinson’s” and who started experiencing symptoms within three years before trial screening. Participants will be assigned randomly to receive one of two doses of K0706 or a placebo, taken daily for nine months.

CereScan, a subsidiary of CereHealth Corporation dedicated to brain imaging and data analytics, will contribute to the study by providing specialized brain scans of study participants.

“We are obliged to offer our services in the research, and ever hopeful that one day soon we will count Parkinson’s Disease among those where advancements in research and technology are combined to find a cure,” John Kelley, CereHealth’s chairman and CEO, said in a press release.

K0706, also known as SCC – 138, is an orally available compound that works as a suppressor of an enzyme called Abl tyrosine kinase, whose activity has been linked to several processes associated with Parkinson’s development, such as oxidative stress and alpha-synuclein-induced neurodegeneration.

Prior studies have demonstrated that K0706 prevents loss of dopamine-producing neurons — the brain cells most affected by Parkinson’s — and eases  behavioral symptoms in animal models of the disease.

Results of SPARC’s pivotal Phase 1 study (NCT02970019), which evaluated the safety and tolerability of ascending doses of K0706 in Parkinson’s patients, showed that the therapy was well-tolerated and allowed the selection of two K0706 doses likely to produce therapeutic effects.

The double-blind, placebo-controlled Phase 2 study (PROSEEK, NCT03655236), also sponsored by SPARC, is now evaluating the safety and effectiveness of the two selected K0706 doses in people with early Parkinson’s disease who are not receiving dopaminergic therapy.

The study’s primary goal is to assess changes in patients’ motor functions  through the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts II and III. As an exploratory goal, researchers also will assess K0706’s impact on the health of dopamine-producing neurons in Parkinson’s patients through the Dopamine Transporter Single Photon Emission Computed Tomography (DaT SPECT) brain imaging.

DaT SPECT is a highly sensitive imaging tool capable of distinguishing people with Parkinson’s from unaffected people even in early stages of the disease. It uses a tracer to “tag” dopamine transporters in the outer membrane of dopamine-producing neurons, which is considered to be a hallmark feature of healthy cells. DaT SPECT images will help determine the density of healthy dopamine-producing neurons in a patient’s brain.

CereScan’s clinic in Littleton, Colorado, will provide DaT SPECT scans of the study participants. It will serve as the SPECT imaging center for Denver Neurological Research, an independent, private clinical research site that is participating in the trial.

“The staggering costs and prevalence in one of our most vulnerable populations, the aged, merits a sustained concentration on the causes of this debilitating disease, and a focus on finding new treatments to staunch its progression,” Kelley added.

Results of this proof of concept trial, if found to be positive, are expected to support the advancement of K0706 into Phase 3 clinical studies in Parkinson’s patients.

To learn more about the trial, visit its webpage.

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Aptinyx to Launch Phase 2 Study of NYX-458 to Treat Cognitive Impairment


Positive preclinical and Phase 1 clinical data support further assessmentof Aptinyx‘s investigational compound NYX-458 for the treatment of cognitive impairment associated with Parkinson’s disease in new Phase 2 studies.

Aptinyx expects to launch a new Phase 2 clinical study in Parkinson’s patients this year, the company announced in a press release.

“So far, 2019 has been marked by the achievement of key milestones and important clinical study results that form the basis for several of our upcoming Phase 2 studies,” said Norbert Riedel, PhD, president and CEO of Aptinyx.

“[W]e reported highly encouraging data from a non-human primate study of NYX-458 … showing its ability to reverse cognitive deficits. We also observed a favorable safety, tolerability, and pharmacokinetic profile with NYX-458 in our healthy volunteer Phase 1 study,” he said.

NYX-458 is a small molecule compound that controls the activity of N-methyl-D-aspartate (NMDA) receptors in the brain. These receptors are involved in the communication between nerve cells, which occur at a structure located at the junction between two nerve cells, called a synapse.

It is thought that loss of dopamine-producing neurons — a hallmark feature of Parkinson’s disease — also impairs the function of NMDA receptors in the brain, leading to cognitive impairment. By controlling their activity, NYX-458 has the potential to restore the function of NMDA receptors and reverse cognitive impairment associated with Parkinson’s.

Preclinical studies have shown that treatment with NYX-458 could lead to fast, strong, and long-lasting improvements in the cognition of animals that had been treated with low doses of a neurotoxin that destroys dopaminergic neurons and induces Parkinson’s symptoms.

Also, treatment with NYX-458 did not interfere with levodopa, a standard therapy for the treatment of motor symptoms associated with Parkinson’s, and did not contribute to worsening of motor symptoms.

These preclinical findings were recently discussed at the 14th International Conference on Alzheimer’s & Parkinson’s Diseases in Lisbon, Portugal.

To explore further explore the potential of the investigational therapy, Aptinyx launched a Phase 1 clinical trial in healthy volunteers. This study was designed to assess the safety, tolerability, and overall stability and metabolism (pharmacokinetics) of NYX-458 in the body.

The randomized, double-blind, placebo-controlled, Phase 1 trial involved 62 healthy volunteers who were treated with NYX-458 administered orally at doses ranging from 10 to 200 mg.

Results showed that NYX-458 was in general safe and well-tolerated by study participants. No serious adverse events associated with the treatment were reported.

Additional analysis also showed that the compound could successfully cross the blood-brain barrier (a semipermeable membrane that isolates the brain from the blood that circulates in the body), behaving as expected in a dose-proportional manner.

Supported by these positive preclinical data and favorable Phase 1 safety and tolerability profiles, the company plans to launch a Phase 2 trial to assess NYX-458 in patients with Parkinson’s disease in the second half of 2019.

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Trial Begins Testing Blood-derived GRF6019 Therapy for Severe Alzheimer’s Disease

GRF6019 severe AD

The first patient has been dosed in Alkahest‘s Phase 2 clinical trial testing its investigational therapy, GRF6019, in individuals with severe Alzheimer’s disease.

The study (NCT03765762) was designed to assess the safety and tolerability of the experimental treatment, as well as its impact on patients’ mental state and capacity to perform daily activities. Researchers will also collect information on overall symptom changes as reported by patients and their caregivers.

The trial is currently recruiting at sites in Arizona and Florida in the United States. Up to 20 participants with severe Alzheimer’s disease, as defined by Mini-Mental State Examination scores between 0 and 10, will be randomized to receive daily intravenous infusions of GRF6019 or a placebo for five consecutive days and followed for up to nine weeks.

Alkahest, and its collaborator Grifols, expect to announce results from this Phase 2 trial during the second half of 2020. For more information about the study, such as clinical site locations and contacts, click here.

“Patients at more advanced stages of Alzheimer’s disease are rarely included in clinical trials, and this novel approach could provide a novel treatment option for these individuals,” Karoly Nikolich, PhD, chairman and CEO of Alkahest, said in a press release.

GRF6019 is an investigational therapy that resulted from the separation of certain proteins from human blood plasma. Blood proteins that promote adverse immune reactions or treatment-patient incompatibilities — such as antibodies and clotting factors — are removed from GRF6019. Researchers believe this depletion process enhances the treatment’s safety and tolerability, and eases its administration. The therapy is also not restricted by blood type matching and is optimized for therapeutic uses.

Preclinical studies have shown that treatment with GRF6019 can improve learning and memory, reduce neuroinflammation, and support brain cells’ health in aged mice, which suggests that the product may hold therapeutic activity for several human neurological disorders, including Alzheimer’s disease.

In a previous open-label trial, called PLASMA (NCT02256306), researchers found that repeated intravenous infusions of plasma from young adult donors, 18 to 30 years old, into patients with mild to moderate Alzheimer’s could significantly improve functional activity in the patients.

“In recent years, it has become evident that there is a complex, multifactorial pathology underlying Alzheimer’s disease that available drugs and those currently in development fail to fully address,” Nikolich said. “Using our deep understanding of the plasma proteome, we have identified specific proteomic factors as the basis for this potential treatment for Alzheimer’s disease.”

Alkahest and Grifols are currently assessing the potential of GRF6019 in a second Phase 2 study (NCT03520998) in 40 patients with mild to moderate Alzheimer’s disease. Results from this study are expected to be announced by the end of 2019.

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UB-311 Vaccine Safe in Mild Alzheimer’s Patients, Phase 2a Trial Shows

UB-311  Phase 2 trial

United Neuroscience’s vaccine candidate UB-311 was safe and well-tolerated in patients with mild Alzheimer’s disease, according to results from a Phase 2a clinical trial.

Patients who participated in this trial are now eligible to enroll in a long-term follow-up study that will continue to assess the vaccine’s safety for 108 weeks.

Trial results, “Active Immunotherapy with UB-311 vaccine: Results from a Phase IIa, randomized, double-blind, placebo-controlled, 3-arm parallel-group, multicenter study” were recently presented during the 14th International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders in Lisbon, Portugal.

UB-311, developed by United Neuroscience, a spin-off of United Biomedical, is a synthetic peptide vaccine that triggers an antibody response against beta-amyloid — whose accumulation in the brain is a hallmark of Alzheimer’s disease — clearing it away without causing potentially harmful inflammation.

Results from a Phase 1 trial (NCT00965588) showed that UB-311 was safe and well-tolerated, and able to trigger high levels of anti-beta-amyloid antibodies in patients with mild to moderate Alzheimer’s disease. The data suggested that the treatment led to a stabilization of patients’ cognitive abilities.

The Phase 2a trial (NCT02551809), conducted at multiple sites in Taiwan, enrolled 43 patients, ages 60 to 90 years, with mild Alzheimer’s dementia. Most participants (81.4%) were APOE-E4 carriers, a genetic factor associated with a higher risk of developing early Alzheimer’s disease.

Patients were randomized to receive intramuscular injections of UB-311 at different doses or a placebo (control). Among those who received the vaccine, one group received a total of seven doses of UB-311 (three priming doses followed by four boosters) and the other group a total of five doses of UB-311 (three priming doses followed by two boosters) and two doses of placebo.

An effective vaccine usually requires more than one administration in the form of a prime-boost. After an initial immunization, a booster injection re-exposes the body to the same antigen, against which the body will create an immune response.

The study’s primary objectives were the safety/tolerability of the vaccine and its ability to trigger an immune response compared with the placebo after 78 weeks. Secondary goals included assessing the vaccine’s effect on patients’ cognitive, neuropsychiatric, and other functioning, including learning and memory assessed by positron-emission tomography (PET) imaging.

Magnetic resonance imaging (MRI) scans were obtained at the beginning of the study, and every three months following vaccination to assess amyloid-related imaging abnormalities (ARIA), meningoencephalitis (inflammation of the meninges and brain), and to track brain volume.

In agreement with recent top-line results, among the 41 patients who completed the 78 weeks, there were no cases of meningoencephalitis or ARIA-edema. The most common adverse events were injection site-related reactions and asymptomatic ARIA-hemosiderin (ARIA-H), which is characterized by small deposits of iron that manifest as dark spots on MRI images.

“To date, UB-311 has been well-tolerated, as continuously assessed by clinical exam and MRI, with over 300 vaccine doses administered from both Phase I and Phase IIa studies,” the researchers wrote.

Patients from this Phase 2 study are eligible to join the Phase 2 extension study (NCT03531710) that will evaluate the long-term safety, tolerability, and potential efficacy of UB-311. Patients will receive three or five doses of UB-311 for 96 weeks, followed by a 12-week follow-up period.

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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.

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First Patient Dosed with VY-AADC Gene Therapy in Parkinson’s Phase 2 Trial


Voyager Therapeutics has begun patient dosing in a Phase 2 trial testing its investigational VY-AADC gene therapy in Parkinson’s patients whose motor symptoms are not responding adequately to oral medication.

The trial, called RESTORE-1 (NCT03562494), is recruiting participants across seven sites in the United States.

VY-AADC is a therapy that delivers the DDC gene, which provides instructions for making the AADC enzyme, directly to brain cells in the putamen region. The enzyme converts the standard-of-care Parkinson’s treatment levodopa into dopamine, the signaling molecule that is lacking in Parkinson’s disease.

The approach is expected to bypass the effects of degenerating dopamine neurons in the substantia nigra, a part of the midbrain, by increasing dopamine levels in the putamen.

In an ongoing Phase 1b trial (NCT01973543), a single administration of the therapy induced robust and durable improvements in patients’ motor function up to three years after treatment.

The treatment also effectively increased AADC enzyme activity, allowing patients to reduce their doses of oral levodopa. Also, patients reported significant improvement in quality of life.

The newly begun Phase 2 trial aims to determine whether VY-AADC is better than a placebo at reducing motor fluctuations in Parkinson’s patients whose symptoms are not effectively controlled with levodopa or related treatments.

The trial is expected to enroll approximately 42 patients who have been diagnosed with Parkinson’s disease for at least four years and are not responding adequately to oral medications. To be eligible, participants must be experiencing at least three hours of OFF time during the day, as measured by a validated, self-reported patient diary.

Participants will be randomized to receive either a single infusion of VY-AADC or a placebo into the brain via surgery. They will be followed for 12 months to determine their changes in motor fluctuations, changes in the ability to perform daily activities, and quality of life.

During the new Phase 2 trial, researchers will also determine the efficacy of treatment delivery by assessing AADC enzyme levels and activity in the putamen through positron emission tomography (PET). Changes in patients’ daily doses of oral levodopa and related medications will also be evaluated.

More information about RESTORE-1, including recruitment details, can be found here.

“Patients with Parkinson’s disease need new therapeutic options, especially as the disease progresses and there is less AADC enzyme in parts of the brain where it is needed to convert levodopa to dopamine,” Mark Richardson, MD, PhD, associate professor, director of Epilepsy and Movement Disorders Surgery at the University of Pittsburgh Medical Center and principal investigator in the RESTORE-1 trial, said in a press release.

The U.S. Food and Drug Administration granted regenerative medicine advanced therapy (RMAT) designation to VY-AADC for therapy-resistant motor fluctuations in Parkinson’s patients.

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