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Phase 2 Trial of Gene Therapy VY-AADC to Include More Parkinson’s Patients

VY-AADC

The ongoing Phase 2 study of the gene therapy VY-AADC will enroll more Parkinson’s disease patients than originally planned, Voyager Therapeutics announced.

The company’s revised trial protocol will include more patients — up from 75 to 100 — in the RESTORE-1 Phase 2 clinical trial (NCT03562494). Voyager also is planning to conduct a parallel Phase 3 study named RESTORE-2, with similar size and design to RESTORE-1.

These updates result from a type B meeting the company had with the U.S. Food and Drug Administration (FDA) in December 2018 and from the written feedback Voyager got from the agency.

“Our recent meeting with the FDA was informative and helps to clarify the expected regulatory pathway for VY-AADC,” Andre Turenne, Voyager’s president and CEO, said in a press release. “We look forward to continuing to engage with the FDA and other regulators as we advance our clinical development program and our work to bring VY-AADC to patients in need,” he said.

Parkinson’s is characterized by progressive loss of dopamine-producing neurons in a brain area called substantia nigra, which is key in controlling movement. This leads to lower levels of dopamine in the putamen, a connected brain region that contains dopamine receptors.

In Parkinson’s patients, the putamen also has markedly reduced levels of the enzyme AADC, which is required to convert levodopa — the gold standard treatment — into dopamine.

Voyager’s VY-AADC consists of a modified and harmless adeno-associated virus to deliver the DDC gene, thereby providing the instructions for making the AADC enzyme directly in the putamen.

RESTORE-1 is currently enrolling individuals diagnosed with Parkinson’s for four years or more and who are not responding well to oral medications. Eligible patients also need to have at least three hours of daily “off” periods — characterized by the return of motor and non-motor symptoms when levodopa’s effects wear off — as assessed by a self-reported patient diary.

Enrolled participants are then randomized to either one-time administration of VY-AADC or placebo surgery.

The double-blind trial’s primary efficacy endpoint, or goal, is on time without troublesome dyskinesia (involuntary, jerky movements), or good “on” time, as measured by a self-reported patient diary at 12 months. The scientists will continue following the patients beyond this timepoint to collect further safety data and to assess how long the therapy’s potential benefits last.

Secondary goals include assessing changes in response to levodopa and in activities of daily living assessed with the United Parkinson’s Disease Rating Scale (UPDRS-II), quality of life with the Parkinson’s Disease Questionnaire, and global function through the proportion of patients with improved Clinical Global Impression score.

The trial also will assess the treatment’s safety, as well as changes in non-motor symptoms with the Non-Motor Symptom Scale. As for biomarkers, the investigators will measure the extension of VY-AADC coverage of the putamen , and AADC enzyme expression and activity in this brain region. Changes in patients’ levodopa dose per day and related medications also will be analyzed.

The company anticipates that RESTORE-1 will take about 15 to 21 months to fully enroll. Recruitment for RESTORE-2 is planned in both active Phase 2 sites and other global locations in the first half of 2020. If positive, results from the Phase 2 and Phase 3 trials could be the basis for the submission of a biologics license application to the FDA covering VY-AADC, according to Voyager.

In June 2018, the FDA granted VY-AADC regenerative medicine advanced therapy (RMAT) designation for the treatment of therapy-resistant motor fluctuations in Parkinson’s patients.

This designation was based on the positive results of a Phase 1b trial (NCT03065192) in 15 Parkinson’s patients, which revealed improvements in motor function and marked reductions in daily use of levodopa and other medications upon treatment with VY-AADC.

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Researchers Evaluate Computer-based Therapy to Ease Fatigue, Improve Motor Function

motor function, nonpharmacological intervention

An ongoing pilot trial is evaluating a computer-based, non-pharmacological cognitive approach to improve motor function and ease fatigue in people with Parkinson’s disease.

Study protocol for a randomised pilot study of a computer-based, non-pharmacological cognitive intervention for motor slowing and motor fatigue in Parkinson’s disease,” appeared in the journal Pilot and Feasibility Studies.

Non-pharmacological therapies may offer effective alternatives to the complications and significant cost of dopaminergic treatment. A team of English researchers set out to develop an approach based on cognitive tasks to lessen fatigue and improve motor function in this patient population.

Advances in the understanding of the brain’s anatomy — such as links between motor and cognitive processes — and of Parkinson’s underpinnings provide the required scientific ground to develop such an approach. Also, previous work from the same team and other researchers had shown that people with Parkinson’s have an impairment in visuospatial tasks, such as mental rotation and mental grid navigation. These tasks were found to activate brain regions such as the supplementary motor area, typically involved in motor control.

Mental rotation is the ability to rotate mental representations of two-dimensional and three-dimensional objects and is related to the brain’s capacity for visual representation; mental grid navigation is the ability to compute a series of imagined location shifts in response to directional cues around a mental grid.

Prior work in 16 people with early-stage Parkinson’s showed improved motor performance after a visuospatial intervention task of mental grid navigation, as evidenced by faster mean onset and velocity. Such results, the team said, indicate that cognitive tasks with visuospatial processing can improve resilience to motor slowing and improve motor function. Such a strategy could become a low-cost option for patients and suitable for home use.

But before this intervention can be considered for a large-scale clinical trial, researchers needed to understand whether the computer-based cognitive training intervention (spatial grid navigation) could lead to significant motor benefits. They also wanted to see whether the improvements extend to aspects such as lessened rigidity and increased motor fluency.

The team designed a randomized single-blind (only patients are unaware of which intervention is expected to be beneficial) pilot study (ISRCTN1256549) to evaluate the feasibility of a larger-scale clinical trial. The trial set out to determine the usability of the devices used to capture movement and finger-tapping data. Tests of finger tapping are routinely conducted to assess bradykinesia, or slowness of movement, and may indicate motor fatigue.

Secondary objectives included assessing changes of at least five points in the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-II) motor examination measure, as well as improvements in movement response times and eased motor fatigue over five 45- to 70-minute sessions involving sequential subtraction or spatial memory control tasks.

Patients were tested at home, at local hospitals or at Wales’ School of Psychology, Bangor University. They did not change their medication or other nonpharmacological regimens. Patients’ hand dominance was assessed before starting the study. Evaluations of quality of life, fatigue, sleep quality, and non-motor symptoms were conducted.

In finger tapping, each hand was tested separately, with the number of taps over 15 seconds and the time between taps analyzed. To evaluate measures of velocity and trajectory, patients held down a button on a response box for four seconds and then reached for a green circle on a screen as quickly and accurately as possible. Eighteen trials were conducted per hand. Action completion time, including movement initiation time and reaching time/velocity, were the primary outcome measures on this task.

The spatial grid navigation task includes an empty grid made up of nine squares, shown for 10 milliseconds. Then, a red start square is displayed for 2.5 seconds and participants are asked to memorize its position. A sequence of five screens is then shown, with two, three or four arrows that indicate movement of the red starting square. The participants must track the position of the red square based on the observed sequence.

At the end of the task, a blue target square is shown with a test grid. The patients then decide whether the position of the blue square matches that of the final position of the presented sequence.

“The results of this study will provide information regarding the feasibility of conducting a larger randomized control trial of non-pharmacological cognitive interventions of motor symptoms in  [Parkinson’s disease],” the researchers stated.

“The longer-term view is to develop an evidence-based, online or app-based platform that could be accessed by people in their own homes alongside other pharmacological or physical treatments to support maintenance of motor slowing and motor fatigue symptoms,” they said.

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For First Time, Precursors of Dopamine Neurons Implanted in Brain of Parkinson’s Patient

Parkinson's stem cells

Precursors of dopamine-producing cells were implanted into the brain of a Parkinson’s patient for the first time. The patient in Japan is the first of seven to receive this experimental therapy.

The approach uses induced pluripotent stem cells (iPSCs), which are developed by reprogramming cells collected from the skin or blood of adults so that they revert to a stem cell-like state and are able to differentiate into almost any cell type.

Scientists at Kyoto University can transform iPSCs into precursors of dopamine-producing neurons. In Parkinson’s, progressive loss of these neurons in a brain area called substantia nigra, and reduced dopamine release in a connected region called striatum, lead to the characteristic motor symptoms.

Last month, neurosurgeon Takayuki Kikuchi implanted 2.4 million dopamine precursor cells into the brain of a Parkinson’s patient in his 50s. The team implanted the cells into 12 centers of dopamine activity over three hours. Stem cell researcher Jun Takahashi and colleagues derived the dopamine precursor cells from iPSCs originally developed from skin cells of an anonymous donor.

“The patient is doing well and there have been no major adverse reactions so far,” Takahashi said in a Nature press release, written by David Cyranoski. The man will be observed over six months. If he does not develop complications, an additional 2.4 million dopamine precursor cells will be implanted into his brain.

Six more Parkinson’s patients are expected to receive this stem cell therapy, which will allow researchers to collect safety and efficacy data by the end of 2020. According to Takahashi, the treatment could reach the market as early as 2023 under Japan’s fast-track approval system for regenerative medicines. “Of course it depends on how good the results are,” he said.

In 2017, Takahashi and his team showed that dopamine-producing neurons transplanted into the brains of monkeys enabled them to move spontaneously over two years. Also, the transplanted cells did not lead to abnormal and jerky movements (dyskinesia), did not develop into tumors — a key concern with iPSCs-based treatments — and did not trigger an immune response not treatable with an immunosuppressive therapy.

In 2014, a Japanese woman in her 70s became the first patient to receive retinal cells derived from iPSCs to treat an eye condition called age-related macular degeneration.

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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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Trial to Test New Imaging Agent for Visualizing Synapses in Living Brain

Imaging agent for synapses

Rodin Therapeutics will evaluate a new imaging agent that allows the visualization of human synapses — the junctions between two nerve cells that allow them to communicate — in the living brain.

Results from the study will guide the company’s upcoming Phase 1b trial of a new therapeutic compound designed to strengthen and increase the number of synapses in patients with neurologic diseases, including Parkinson’s.

Several neurological and psychiatric diseases are characterized by defective synapses. However, there is currently no way to visualize synapses in the living brain. Tissues would need to be sampled, an invasive and unwanted procedure.

The new imaging agent, a radiotracer called [11C]UCB-J, targets the synaptic vesicle glycoprotein 2A (SV2A) and is used in positron emission tomography (PET). This protein regulates the release of neurotransmitters — chemical messengers used by the nervous system to transmit messages between neurons, or from neurons to muscles — at the synapse.

PET imaging uses small amounts of radioactive materials, called radiotracers, along with a special camera and computer to help evaluate organ and tissue function.

The trial, which will include both healthy volunteers and patients with Alzheimer’s disease, will produce brain scans following administration of the radiotracer. Participants will undergo scans at the beginning of the trial (baseline) and 28 days later.

The trial will determine the radiotracer’s robustness and potential usefulness in future trials.

“Most neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s, are associated with deteriorating synapses — but until now, physicians and researchers have not been able to measure synaptic density in a living patient. This PET scan should allow us to visualize brain synaptic density in patients and possibly track their response to therapies over time,” J. Michael Ryan, MD, Rodin’s chief medical officer, said in a press release.

“Measuring synaptic density in a living human being holds tremendous potential for the diagnosis and treatment of a variety of neurologic diseases. We’re excited to be one of the first research centers to utilize this new imaging technology,” said Peter Paul De Deyn, MD, Ph.D., director of the Alzheimer’s Research Center Groningen, the Netherlands, one of the centers where the trial will take place.

“This tool has the potential to shape future clinical trials by offering an early signal about whether an investigational drug is driving molecular and structural changes in the brain,” said Philip Scheltens, MD, Ph.D., who directs the Alzheimer’s Center at VUmc, Amsterdam, another trial center. “We can then take the next step and assess whether those changes lead to functional and cognitive improvements in patients with neurodegenerative diseases.”

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Aptinyx’s Investigational Parkinson’s Therapy NYX-458 Enters Phase 1 Clinical Testing

NYX-458 Parkinson's therapy

Aptinyx has launched a Phase 1 clinical trial of NYX-458, a potential treatment for cognitive impairment in Parkinson’s disease patients.

The randomized, double-blind, placebo-controlled trial will be conducted in roughly 62 healthy volunteers to evaluate the safety, tolerability, and pharmacokinetics of the compound. Pharmacokinetics refers to a drug’s absorption, bioavailability, distribution, metabolism, and excretion in the body.

Patients will receive both single and repeat dosing of NYX-458 at multiple dose levels to determine the optimal dosage for future Phase 2 studies. The company is planning studies to test the effectiveness of the investigational therapy next year.

“Based on the compelling preclinical evidence of NYX-458 in reversing cognitive impairment, we are excited to initiate this first-in-human study and advance NYX-458 as a potential treatment for this very common and highly limiting, but poorly treated, symptom of Parkinson’s disease,” Torsten Madsen, MD, PhD, chief medical officer of Aptinyx, said in a press release.

NYX-458 is a small molecule therapy that functions by regulating the activity of N-methyl-D-aspartate (NMDA) receptors, which are found in nerve cells, enhancing synaptic plasticity and improving nerve cell communication. Synapses are the junctions between two nerve cells that allow them to communicate; synaptic plasticity refers to the ability of synapses to strengthen or weaken over time.

Synaptic plasticity contributes to learning, memory, and cognition, all of which are often impaired in Parkinson’s patients.

Earlier this year, Aptinyx presented positive preclinical data of NYX-458 during the 2018 Advances in Alzheimer’s and Parkinson’s Therapies Focus Meeting in Torino, Italy.

The study, which was conducted in a non-human primate model of Parkinson’s disease, showed that 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.

“… NYX-458 has the potential to be a meaningful therapy for patients suffering from some of the most devastating symptoms of Parkinson’s disease,” Cassia Cearley, PhD, vice president of research at Aptinyx, said in a press release at the time. “These results in a relevant and highly translatable model warrant the advancement of NYX-458 into clinical studies.”

So far, Aptinyx’s chemistry and discovery platform has generated three therapeutic candidates, NYX-2925, NYX-783, and NYX-458, currently in clinical development for the treatment of various nervous system disorders. This platform is unique in that it discovers compounds that work to regulate — rather than block or over-activate — NMDA receptors to enhance synaptic plasticity, which is the foundation of nerve cell communication.

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Feedback from Parkinson’s Patients Can Help Improve Trial Recruitment, Retention, Study Says

clinical trial feedback

Getting the perspective of Parkinson’s disease patients on their motivations and experiences participating in clinical trials can help increase recruitment and retention of future studies, a report suggests.

Although preventable, one of the most common reasons Phase 2 or 3 trials fail is because not enough patients participate. This could be due to inadequate recruitment or because patients drop out during the trial.

The report, “Recruitment and Retention in Clinical Trials of Deep Brain Stimulation in Early-Stage Parkinson’s Disease: Past Experiences and Future Considerations,” published in the Journal of Parkinson’s Diseaseevaluated patient responses after a pilot study on the safety and tolerability of subthalamic (STN) deep brain stimulation (DBS) for the treatment of early-stage Parkinson’s disease.

DBS is commonly used to treat patients with advanced Parkinson’s who no longer respond to available medications and are unable to adequately manage their symptoms.

The U.S. Food and Drug Administration also recently expanded the use of DBS — which requires surgery to implant a device to stimulate targeted regions of the brain — to patients with mid-stage disease who also respond poorly to standard medications.

Vanderbilt University in Nashville, Tennessee, completed a clinical trial (NCT00282152) that included 30 patients, ages 50 to 75, with early-stage Parkinson’s disease. The participants were randomized to receive either optimal drug therapy (ODT) or ODT plus STN-DBS and followed for two years.

At the end of this pilot study, participants were asked to complete a survey regarding their experiences participating in the trial. Their responses were compared with those from an independent survey that used Fox Insight, an online clinical study platform established by The Michael J. Fox Foundation for Parkinson’s Research, to survey early-stage Parkinson’s patients who were considering possibly participating in a trial for DBS.

The pilot trial was specifically designed to collect preliminary safety and tolerability data necessary to conduct an FDA-approved Phase 3 trial (IDE#G050016) to investigate the hypothesis that DBS in patients with early Parkinson’s can slow disease progression.

Importantly, patient experiences were expected to inform the feasibility of scaling up recruitment for the future trial.

Results revealed that the primary motivation for participating in a clinical trial was the desire to advance medical research, cited by 85% of trial respondents. This was followed by a desire for the best medical treatment, for 70%, and for 59%, a desire to learn more about Parkinson’s disease. Similarly, altruistic motivations were also seen in the Fox Insight survey.

The most frequently listed fear that could impact trial participation was surgery-related concerns, in 44% of participants. Although 37% of the pilot study participants did not report any burdens, the most common burdens associated with clinical trials were financial commitments such as time off work and traveling costs (30%), as well as some of the therapeutic interventions such as neuropsychological testing (26%), and the weeklong therapeutic washout periods — without medication (26%).

The pilot study implemented a rigorous informed consent progress aimed at educating potential participants on their role in the study. Most participants responded positively to this approach. Providing sufficient education at the start of the trial may decrease the drop-out rate. In fact, only 3% of participants did not complete the study. As a result, this approach of informed consent will be used in the upcoming Phase 3 trial, according to the authors.

Getting patient perspectives is a new strategy that could improve clinical trial recruitment and retention. Whereas most clinical trials were solely designed by physicians, now, as the authors suggest, by asking patients about their experiences and including their feedback in trial development, “the focus shifts away from the physician and toward the patient.”

“By understanding the motivations and barriers to trial participation of past and potential subjects, we attempt to predict feasibility of recruitment in the future pivotal trial,” the authors wrote. “The fundamental similarities of these two cohorts of patients with early-stage [Parkinson’s disease] suggest that the planned multicenter, pivotal trial will experience similarly successful recruitment and retention as the single-center pilot trial.”

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Source: Parkinson's News Today

Identifying Biomarkers of Inflammation Among Goals of Parkinson’s Study by Longevity Biotech and Veterans’ Center

Longevity Biotech study

Longevity Biotech announced plans for a clinical study aiming to identify potential blood-based markers of inflammation that originates in the immune system, biomarkers that may work to better diagnose Parkinson’s and recognize the disease’s different stages.

The study, being run with the support of The Michael J. Fox Foundation for Parkinson’s Research, will also advance early evaluations of the company’s therapeutic candidate LBT-3627.

The two-year study will launch at the Corporal Michael J. Crescenz Veterans Affairs Medical Center,  part of the Philadelphia Parkinson’s Disease Research, Education and Clinical Centers.

The immune system plays a critical role in neurodegenerative diseases, including Parkinson’s. The study will use machine learning techniques to identify immune-based inflammatory biomarkers “that could provide clinically relevant diagnostic information,” Scott Shandler, PhD, co-founder and CEO of Longevity Biotech, said in a press release.

“The identification of these [immune-based inflammatory] markers would have a tremendous impact on the pace of disease modifying therapeutic development for Parkinson’s disease patients by providing a new metric to track disease progression while possibly identifying new disease targets as well,” he added.

Study researchers will be looking not only to expand knowledge into the underlying mechanisms of Parkinson’s, but also to correlate new and existing blood-based markers, such as the protein alpha-synuclein, with standard clinical scores from the Unified Parkinson’s Disease Rating Scale (UPDRS). This scale uses questions to assess both motor and non-motor symptoms associated with Parkinson’s.

In a preclinical setting — ex vivo, meaning outside a living organism — researchers will also examine the potential efficacy of LBT-3627 using human immune cells. The investigative compound is a small protein designed to mimic naturally occurring molecules that activate a family of receptors known for their neuroprotective and anti-inflammatory activities. As such, LBT-3627 is expected to work to balance immune responses and reduce inflammatory damage done to the brain by immune cells.

Previous studies in mice disease models found evidence that LBT-3627 can protect dopaminergic neurons from degeneration, one of the hallmarks of Parkinson’s disease.

“The goal is to convert T cells, which are key actors in the adaptive immune system, from an inflamed, neurodegenerative state to a more healthy, neuroprotective one,” said Jenell Smith, PhD, a lead scientist at Longevity Biotech.

“LBT-3627 has demonstrated robust neuroprotective results in animal models of Parkinson’s disease to date and we will continue testing the effects of LBT-3627 on human immune cells as part of this study,” Smith concluded.

The release did not specify if this study is already underway.

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Herantis Announces New Program to Develop Non-Invasive CDNF for Parkinson’s Treatment

non-invasive CDNF development

Herantis Pharma is launching a development program for non-invasive cerebral dopamine neurotrophic factor (CDNF) as a treatment candidate for patients with Parkinson’s disease, the company recently announced.

Currently, the investigational treatment needs to be administered directly into the brain using an implanted delivery system suited for Parkinson’s patients. Under the new program, Herantis will seek new methods of delivering the therapy to patients.

A new licensing agreement with the University of Helsinki will grant the company worldwide, exclusive rights for a non-invasive CDNF-based treatment.

“Non-invasive CDNF is an important expansion to our existing patent estate and strengthens the profile and value of our CDNF program,” Pekka Simula, Herantis’ CEO, said in a press release. “We believe CDNF can make a significant difference in the treatment of Parkinson’s disease and we look forward to exploring the new possibilities a non-invasive administration could offer to provide the best product for the benefit of patients.”

CDNF is based on a protein naturally present in blood and cerebrospinal fluid — the liquid filling the brain and spinal cord. Preclinical studies showed that it has neuroprotective and neurorestorative properties in brain cells that generate the neurotransmitter dopamine, suggesting its potential to help Parkinson’s patients.

In 2017, Herantis began a Phase 1/2 clinical trial testing the safety and tolerability of CDNF. In this study, the therapy cannot be delivered as a pill or injection because the body will not transport it to the brain. So a neurosurgeon needs to implant a drug delivery system in patients’ brains.

In the randomized, double-blind trial (NCT03295786), participants will receive monthly infusions of either CDNF (mid- or high-dose) or placebo for six months. Herantis is recruiting 18 Parkinson’s patients for the trial.

The study is being conducted at the Karolinska University Hospital and the Lund University Hospital, both in Sweden, and the Helsinki University Hospital in Finland.

Prior proof-of-concept studies showed that the treatment candidate may ease both motor and non-motor symptoms of Parkinson’s, as well as stop disease progression.

“We have previously shown that CDNF protects and recovers neurons from degeneration, neuroinflammation and endoplasmic reticulum stress, critical contributors to many neurodegenerative diseases,” said Mart Saarma, PhD, who has been leading the research into CDNF at the University of Helsinki.

Saarma considers the development of CDNF into an investigational product “exciting” and says he is looking forward to supporting Herantis in the process. “Our recent discoveries provide an opportunity to target numerous indications beyond Parkinson’s with simpler administration and broader distribution while maintaining the full potential of CDNF,” he said.

Besides Parkinson’s, Herantis is also developing CDNF as a potential treatment for patients with amyotrophic lateral sclerosis.

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Intense Exercise Helps Early Parkinson’s Patients Retain Motor Skills, Phase 2 Trial Shows

exercise

High-intensity exercise is not only safe and feasible, but it can also delay disease progression in early stage Parkinson’s patients, results of a Phase 2 trial report.

The study, “Effect of High-Intensity Treadmill Exercise on Motor Symptoms in Patients With De Novo Parkinson Disease,” was published in the journal JAMA Neurology.

SPARX, or a Study in Parkinson Disease of Exercise (NCT01506479), was a Phase 2 multicenter trial led by researchers at the University of Colorado’s UC Health. It addressed if high-intensity exercise was safe for people in very early stages of the disease, and what physical intensity might be of most benefit to them.

It enrolled 128 people with early Parkinson’s disease, between 40 and 80 years old and diagnosed within five years. None were   taking any Parkinson’s medications.

Participants were randomly assigned to one of three groups — moderate exercise, vigorous exercise, or usual care — for six months.

Disease progression was assessed at the study’s start and again after six months using the Unified Parkinson’s Disease Rating Scale (UPDRS) Motor Score: the higher the score, the greater a patient’s motor disability.

Exercise intensity was measured using heart rate monitors at all workout sessions.

People in the moderate group engaged in treadmill exercises four times a week, bringing their heart rate up to 60 to 65 percent of maximum capacity. Those in the vigorous group also exercised on a treadmill with the same frequently, but brought their heart rates to 80 to 85 percent of maximum.

At six months, the UPDRS score for the high-intensity exercise group had barely changed, indicating these patients’ motor skills did not worsen.

But these scores rose on average by 8 percent among patients in the moderate exercise group, and by 15 percent in those given usual care, indicating a worsening in movement and motor skills in these people. 

No serious side effects were reported in any group, and adverse events were considered “anticipated,” the researchers wrote, including falls, pain, muscle and joint disorders.

These results show that high-intensity exercise can preserve movement abilities in early stage Parkinson’s patients and can do so safely if exercise programs are guided by specialists.

They also warrant further investigation in a Phase 3 trial evaluating more fully the benefits of regular high-intensity exercise in Parkinson’s patients, the team said.

“The study shows that neurologists can rest assured that it’s safe and feasible for their patients to exercise at a high intensity. That’s huge. We can get people started right away on exercise habits, when that is easier to do,” Margaret Schenkman, director of the Physical Therapy Program at the UC School of Medicine, and principal investigator for the SPARX study, said in a UC Health news release.

Previous studies have shown that exercise can help Parkinson’s patients maintain balance, mobility, and the ability to perform daily routines while preserving a better quality of life.

But studies to date have only tested moderate exercise programs, and most have not addressed whether exercise intensity might affect disease severity or its progression.

 

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