Posts

MJFF Nationwide Event Series ‘Parkinson’s IQ + You’ Kicks Off This Fall

Parkinson's IQ + You

A new nationwide event series aims to empower people with Parkinson’s (PD) and their caregivers to manage the disease, learn about research participation, and plug into local resources.

Called “Parkinson’s IQ + You,” the effort is presented by The Michael J. Fox Foundation (MJFF). The events seek to support PD families in learning more about all facets of the disease — what a comprehensive care team looks like, how to achieve optimal communication between patients and physicians, the latest in treatments, and the benefits of joining clinical trials.

Kick-off events are slated this year for Atlanta on Sept. 14, and southern California, in Anaheim, on Dec. 14. More sessions will come next year, including one in Phoenix on Jan. 11. Registration is free. This year’s events will be hosted by Larry Gifford, a patient and host of the “When life gives you Parkinson’s” weekly podcast.

“Between its symptoms and progression, Parkinson’s can present unique challenges for those of us who live with the disease, but also for our loved ones who support us,” John L. Lipp, a writer, nonprofit executive director, and Parkinson’s patient, said in a news release.

“I often say, ‘I can’t control my Parkinson’s, but I can control how I respond to it.’ Parkinson’s IQ + You will offer people in the community, including me and my husband, an opportunity to learn from other patients and families and from experts in the field, so that we can turn education today into action tomorrow,” Lipp said.

Crafted to support care partners and people with Alzheimer’s at every disease stage, the series will feature a variety of panel participants, including patients and their caregivers, to reflect the community’s diversity and the disorder’s variability. The organizers note that PD symptoms and progression vary significantly, making each Parkinson’s experience unique.

Each full-day event will feature interactive programming, as well as an exposition of local resources. Called Parkinson’s Partner Expo, this portion will include representatives from movement disorder centers and patient advocacy organizations, speech and physical therapists, and clinical trial teams.

There also will be panels and sessions on topics such as understanding Parkinson’s and living well with it. During a related forum called “If I Knew Then What I Know Now,” a patient and caregiver will share experiences and strategies. There also will be a session on “Building Your Care Team.”

To help people with Parkison’s and their caregivers understand the advantages of seeing a specialist, what to expect during visits, and how to optimize each one, each event will feature a demonstration of what a typical appointment might be.

“Patients are the force driving our research priorities and our urgent mission to end Parkinson’s,” said Todd Sherer, PhD, the foundation’s CEO. “The foundation is committed to ensuring all people with Parkinson’s, and their families, are empowered to make decisions about treatment and care. And we want to work side by side in partnership with patients to advance Parkinson’s research.”

The series includes complimentary meals, and is funded by Acadia Pharmaceuticals, with additional support from MJFF biotech and pharmaceutical partners.

“The Parkinson’s IQ + You program has been uniquely designed to bring much-needed support and information to the Parkinson’s community,” said Rob Kaper, MD, Acadia’s senior vice president and global head of medical affairs.

“We look forward to this national series of events across the country, which will offer attendees the opportunity to interact with healthcare experts and other people with Parkinson’s and their families, and ask important questions about disease management,” he said.

The post MJFF Nationwide Event Series ‘Parkinson’s IQ + You’ Kicks Off This Fall appeared first on Parkinson’s News Today.

Phase 1 Trial to Explore RDN-929’s Safety in Treating Brain Diseases by Protecting Synapses

Treat Neurodegenerative Diseases

Rodin Therapeutics has started a Phase 1 clinical trial to explore the safety of its synthetic compound, RDN-929, to treat neurodegenerative diseases, including Alzheimer’s and Parkinson’s, by protecting synapses.

The trial (NCT03668314), is designed to assess the safety, tolerability, pharmacokinetics — how the body affects a medicine — and pharmacodynamics — the interactions between the body and a compound — of single and multiple ascending doses of RDN-929 in approximately 92 healthy adult volunteers.

The study, conducted in the Netherlands, is currently recruiting participants.

“We’re thrilled to be in the clinic with our lead compound, which represents a novel approach to treating neurodegenerative diseases such as Alzheimer’s,” Adam Rosenberg, president and CEO of Rodin, said in a press release.

“This Phase 1 trial is an important milestone for us as we advance an ambitious clinical strategy,” Rosenberg said.

The study is divided in three parts. In the first part, researchers will randomly assign 48 adult participants to receive a single administration of one of six ascending doses of RDN-929, or a matched placebo.

Part two will select 12 healthy elderly subjects (ages 55–80) from the first group, who will undergo two crossover treatment periods, separated by a washout period of at least seven days for the medication to clear their system. In the first period, participants will receive a single dose of RDN-929 selected based on data from part one, either while fasting or with food. This will be followed by a second administration of a single dose of RDN-929, with the fasting or food status reversed.

The last part of the trial will explore multiple ascending doses of RDN-929 in up to four groups of eight healthy elderly subjects (at least three of each gender). The doses will be selected by an independent safety review committee, upon an interim safety analysis and approval by the ethics committee.

Researchers here will administrate once daily RDN-929 or placebo for 12 days. Escalation to the next higher dose will be based upon a review of the safety and tolerability data.

RDN-929 is a synthetic compound developed to selectively inhibit the histone deacetylase (HDAC)-CoREST complex. This complex is known to be involved in preventing the expression of certain neuronal genes.   RDN-929 is designed to rebalance neuronal genes’ levels, strengthen brain cell communication (synaptic function), and promote the formation of new synapses.

Gene expression is the process by which information in a gene is synthesized to create a working product, like a protein. 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.

Preclinical data has shown that RDN-929 is both effective and suitable for long-term treatment. Rodin believes that its compound may represent a new way of treating over 100 brain disorders that are characterized by synaptic loss and dysfunction, referred to as synaptopathies.

“We believe that directly targeting and strengthening synapses will lead to meaningful improvements in clinical symptoms, and we are hopeful that this approach can help patients across a broad range of disease severities,” Rosenberg stated.

Rodin is also sponsoring an ongoing, non-therapeutic clinical trial (NCT03577262) to explore the performance of a new radioactive tracer, designed to measure synaptic density in the living brain using positron emission tomography (PET) scans.

Data from these two studies will provide useful information to plan future clinical trials of RDN-929 in patients with Alzheimer’s, Parkinson’s, frontotemporal dementia, and other synaptopathies.

The post Phase 1 Trial to Explore RDN-929’s Safety in Treating Brain Diseases by Protecting Synapses appeared first on Parkinson’s News Today.

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

RESTORE-1 Voyager VY-AADC

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.

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

Investigational Gene Therapy AXO-Lenti-PD Tested in Phase 1/2 Clinical Trial in Parkinson’s Patients

AXO-Lenti-PD

The first patient has been dosed in Axovant’s Phase 1/2 clinical trial testing the investigational gene therapy AXO-Lenti-PD for the treatment of Parkinson’s disease.

The patient reported no complications associated with surgery or administration of the therapy and was discharged as planned in the initial trial design. Preliminary data from the first group of patients treated in the trial are expected to be announced during the first half of 2019.

Currently recruiting participants, the trial (NCT03720418) is expected to enroll about 30 patients ages 48-70 who have had bilateral idiopathic (of unknown cause) Parkinson’s disease for at least 5 years.

The study, being conducted in the United Kingdom and France, consists of two parts. In part A, researchers will evaluate the safety and tolerability of increasing doses of the investigational gene therapy, and select the optimal dose to be used in further testing.

Part B is a randomized, double-blind phase in which patients will receive either the designated dose from Part A or an imitation surgical procedure (ISP). Patients will be followed for about 6 months to assess AXO-Lenti-PD’s safety and potential to enhance motor function and improve movement control.

AXO-Lenti-PD, also known as OXB-102, is a gene therapy that uses a harmless virus-based system to deliver three genes that encode critical enzymes involved the synthesis of dopamine — the signaling molecule, or neurotransmitter, produced at low levels in Parkinson’s patients.

This treatment is expected to provide significant and long-lasting clinical benefits to patients with Parkinson’s disease upon a single administration.

The gene therapy was initially designed by Oxford BioMedica, which in June 2018 granted the exclusive worldwide rights over AXO-Lenti-PD’s development and marketing to Axovant Sciences.

“We are very excited to bring AXO-Lenti-PD into clinical development and believe it will be an important new therapy for patients with Parkinson’s disease who suffer from motor fluctuations on the current standard of care,” Pavan Cheruvu, MD, the CEO of Axovant, said in a press release. “This marks the first of our gene therapy programs to enter the clinic, and our focus now is on rapid execution of the clinical study.”

A recently completed Phase 1/2 trial of ProSavin (NCT00627588), AXO-Lenti-PD’s predecessor, demonstrated favorable safety and tolerability and a significant improvement of motor function at 6 and 12 months in Parkinson’s patients. This benefit was sustained for up to six years.

Compared with ProSavin, preclinical studies of AXO-Lenti-PD showed increased production of the key enzymes, as well as at least a fivefold greater potency in improving behavior and movement in an animal model of the disease.

“Building upon the evidence of safety and durable improvements in motor symptoms seen up to six years in the prior clinical study of ProSavin, we feel a sense of urgent responsibility to accelerate the development of AXO-Lenti-PD,” Cheruvu said.

“Mid- to late-stage Parkinson’s disease remains a challenge to treat, with current therapies leading to debilitating adverse events and unpredictable therapeutic effects over time,” said Stéphane Palfi, MD, PhD, coordinating investigator of the AXO-Lenti-PD trial.

“We are pleased to advance AXO-Lenti-PD in the clinic and are eager to see the trial expand upon the long-term safety and efficacy results we observed in the Phase 1/2 clinical trial of ProSavin,” he said.

The post Investigational Gene Therapy AXO-Lenti-PD Tested in Phase 1/2 Clinical Trial in Parkinson’s Patients appeared first on Parkinson’s News Today.

Participation of Early Parkinson’s Patients in Clinical Trials Crucial to Finding Cure, Expert Says

The time between diagnosis and implementation of symptomatic treatment is critical in the effort to find a cure for Parkinson’s disease.
However, many early Parkinson’s patients wait too long before seeking medical attention, leaving researchers with a small group of candidates for clinical trials, says Robert A. Hauser, MD, the director of the Parkinson’s & Movement Disorder Center at the University of South Florida.
In his commentary, “Help cure Parkinson’s disease: please don’t waste the Golden Year,” published in the journal npj Parkinson’s disease, Hauser stresses the importance of early Parkinson’s patients participating in clinical trials before they start taking symptomatic medications.
The discovery that Parkinson’s is associated with aggregation of misfolded alpha-synuclein proteins in the central nervous system suggests there are many potential targets for therapeutic intervention.
Researchers are enthusiastic about the idea that the disruption of this process, or removing toxic aggregates, can slow or stop disease progression. Unfortunately, there are still no validated biomarkers, such as a simple blood test, that can help monitor disease progression or test promising therapies in Parkinson’s patients.
So far, the most common way to test a therapeutic candidate is to assess its capacity to slow the progression of clinical signs and symptoms compared with placebo over time in patients with early Parkinson’s who are not yet receiving symptomatic Parkinson’s medications — such as levodopa, dopamine agonists, and MAO-B inhibitors.
However, this can prove to be a challenge, since patients with early Parkinson’s disease can only be followed, without the use of symptomatic medication, for about six to 12 months, what Hauser calls the “Golden Year.” After this, many patients will need medication to relieve symptoms.
“The critical time of about one year from when the patient can be diagnosed with early PD [Parkinson’s disease] based on mild classic motor features until they truly require symptomatic therapy can be considered the Golden Year,” Hauser said in a press release. “It is during this early, untreated phase, that progression of clinical symptoms reflects the progression of the underlying disease.”
Interference from symptomatic medications makes it difficult for researchers to tell if the potential treatment being tested is slowing disease progression or if they are just seeing effects from those other therapies.
However, patients with early Parkinson’s who are available to enroll in a clinical trial and whose symptoms are mild enough are in short supply.
Therefore, to test promising potential disease-modifying therapies, patients with early Parkinson’s have to be identified and referred to clinical trials before they go on symptomatic medications. Unfortunately, this is often not the case.
“If the time period over which we test the intervention is short, we reduce our ability to identify a difference between the intervention and placebo. If the time period over which we attempt to test the medication is too long, a substantial proportion of patients may require institution of symptomatic therapy and we lose our ability to monitor clinical disease progression during the observation period,” Hauser wrote.
Patients often put off seeing their physician until their motor symptoms require symptomatic treatment. Additionally, there are often unwanted delays in the time between setting the

Source: Parkinson's News Today

Trial Fails to Show Benefits of Hydrogen-saturated Water in Parkinson’s Patients

Drinking hydrogen-enriched water does not provide therapeutic benefits to patients with Parkinson’s disease, results from a Japanese clinical trial revealed.
The study,“Randomized, Double-Blind, Multicenter Trial of Hydrogen Water for Parkinson’s Disease,” was published in the journal Movement Disorders.
Parkinson’s disease is characterized by reduced levels of dopamine (a critical brain signaling molecule) caused by the degeneration and death of brain cells responsible for its production, called dopaminergic neurons.
It is not yet fully understood what triggers the disease, but the underlying cellular mechanisms involved in Parkinson’s disease are known to promote and be supported by higher levels of oxidative stress.
For cells to create energy, they “breathe” oxygen received by the food we eat and the air we breathe, and as a result, reactive molecules are created. These residual molecules are the free radicals responsible for oxidative stress.
In addition, in our everyday life, our bodies are exposed to reactive oxygen species (ROS) as a result of the environment around us. When something doesn’t work well in the energy extraction process and cells become full of ROS compounds, oxidative stress occurs.
As such, antioxidant agents that could help reduce and manage the levels of the damaging oxidant molecules may represent an attractive strategy to ease Parkinson’s symptoms and prevent their progression.
Molecular hydrogen (H2) reacts with strong oxidants in cells, and its potential for preventive and therapeutic applications has been proposed. Hydrogen has a number of advantages that demonstrate extensive effects, and it can rapidly diffuse into tissues and cells, and it does not disturb metabolic reactions or affect signaling ROS.
There are several methods to ingest or consume hydrogen, such as inhaling hydrogen gas, drinking hydrogen-dissolved water, or injecting hydrogen-dissolved saline.
Japanese researchers explored the potential benefits of the antioxidant activity of hydrogen in patients with Parkinson’s disease.
An earlier pilot study in 18 levopoda-medicated Parkinson’s patients revealed that hydrogen-enriched water might provide therapeutic benefits for these patients.
After 48 weeks of therapy with hydrogen-enriched water, the patients experienced a mean reduction of 5.7 points in total Unified Parkinson’s Disease Rating Scale (UPDRS) scores, whereas placebo-treated patients scores worsened by 4.1 points during the same time period.
The UPDRS is a comprehensive 50-question assessment of both motor and nonmotor symptoms associated with Parkinson’s disease.
To further explore the therapeutic activity of hydrogen-enriched water, researchers designed a new trial (UMIN000010014) that enrolled 178 patients across 14 hospitals in Japan. Among the participants, 154 were receiving treatment with levopoda during the study period.
The participants were randomized to drink daily one liter of Ecomo International’s hydrogen water 7.0 or placebo water for up to 72 weeks.
Evaluation of disease status by UPDRS scores failed to demonstrate significant improvements after the 72 weeks of treatment with hydrogen-enriched water compared to placebo.
In this new study the treatment did not promote any changes between the two groups in each of the UPDRS individual parts, Parkinson’s Disease Questionnaire-39 (PDQ-39) score, and the Hoehn and Yahr stage (all standard measures to assess Parkinson’s status and progression).
Researchers believe these results could be due to the fact that hydrogen doses being administrated with hydrogen water 7.0 are too low and act more as a placebo.
In addition, the patients included

Source: Parkinson's News Today

Phase 2 Trial Shows Nilotinib Potential to Modulate Dopamine in Parkinson’s

Nilotinib Phase 2 trial

Nilotinib can modulate dopamine levels and metabolism, as well as prevent the formation of toxic alpha-synuclein aggregates, according to recent data from a Phase 2 clinical trial.

These findings suggest that Novartis’ investigational therapy has the potential to promote long-term benefits in patients with Parkinson’s disease.

The study, “Nilotinib increases dopamine metabolism and reduces oligomeric: total alpha-synuclein ratio in Parkinson’s disease,” was recently presented during the 2018 World Congress on Parkinson’s Disease and Related Disorders (IAPRD), Lyon, France.

Nilotinib is available under the brand name Tasigna as an approved treatment for certain types of leukemia. It blocks the activity of a protein called BCR-ABL that is known to support cancer development. But this protein also is intimately linked to several mechanisms in the brain, such as oxidative stress and alpha-synuclein-induced neurodegeneration, which play critical roles in Parkinson’s and other brain disorders.

Results of a small proof-of-concept Phase 1 trial (NCT02281474) performed at Georgetown University in Washington, D.C., revealed that treatment with two different doses of Nilotinib — 150 mg and 300 mg — could improve Parkinson’s patients’ motor skills and cognitive abilities. In addition, the treatment showed the potential to reduce levels of the protein alpha-synuclein, which is believed to contribute to destruction of brain nerve cells in Parkinson’s disease.

In the ongoing Phase 2 trial (NCT02954978) a total of 75 patients with mid-stage Parkinson’s disease with mild cognitive impairment were randomized to take one of four tested oral doses of Nilotinib -—150 mg, 200 mg, 300 mg, and 400 mg — or a placebo.

After a single treatment researchers evaluated several biomarkers of the disease, including the levels of alpha-synuclein and dopamine derivate compounds in patients’ cerebrospinal fluid (CSF).

The data revealed a significant increase in homovanillic acid (HVA) and DOPAC levels, suggestive of enhanced production and metabolism of dopamine just one to four hours after treatment.

Although researchers could not find significant changes in CSF total alpha-synuclein levels, low-dose Nilotinib therapy (150 mg and 200 mg) resulted in a reduction of the levels of abnormally clustered and toxic alpha-synuclein.

“The significant reduction of oligomeric alpha-synuclein, which is expected to increase in the CSF of Parkinson’s disease patients as the disease progresses, suggests that Nilotinib may reduce misfolded alpha-synuclein accumulation and have a long-term disease modifying effect,” researchers wrote.

“These results suggest Nilotinib, in a dose dependent manner, may have a symptomatic effect through modulation of brain dopamine levels. Additionally, the significant reduction of oligomeric alpha-synuclein, which is expected to increase in the CSF of PD patients as the disease progresses, suggests that Nilotinib may reduce misfolded alpha-synuclein accumulation and have a long-term disease modifying effect,” researchers wrote.

The team will continue the analysis of the collected data to further explore the impact of Nilotinib treatment on disease biomarkers’ levels both in the blood and CSF, after a single administration and 52-week daily treatment regimen.

A new Phase 2 trial, NILO-PD (NCT03205488), currently recruiting 135 participants, will further investigate the potential of Nilotinib in patients with moderate-to-advanced Parkinson’s symptoms.

The study will take place at 25 sites across the United States. It will compare the safety and effects on patients’ motor functions of once-daily Nilotinib versus placebo treatment, for up to 12 months.

The post Phase 2 Trial Shows Nilotinib Potential to Modulate Dopamine in Parkinson’s appeared first on Parkinson’s News Today.

Source: Parkinson's News Today

Imaging Tracer with Potential to Bolster Clinical Trials of Parkinson’s and Its Treatments Favored by EMA

123I-FP-CIT SPECT tracer

The European Medicines Agency (EMA) endorsed an imaging test that can help in identifying Parkinson’ patients with early stage disease but likely to progress quickly — people who might be best suited to taking part in clinical trials.

Development of this clinical assessment tool — which targets disease biomarkers — came through collaborative work involving Critical Path for Parkinson’s (CPP) Consortium, a part of the Critical Path Institute (C-Path), the non-profit group Parkinson’s UK, and several pharmaceutical companies.

“This endorsement from the European Medicines Agency represents many years of hard work and incredible collaboration among companies, universities, and charities facilitated by the Critical Path Institute,” Diane Stephenson, executive director of CPP, who led the effort, said in a press release.

“Through our global project, we’ve been able to bring all the data and expertise together to make a powerful case, so we’re delighted that this endorsement from the EMA will improve the quality and chances of success for future trials of Parkinson’s treatments,” Stephenson added.

The method requires the intravenous injection of a radioactive tracer called 123I-ioflupane, or 123I-FP-CIT, which can be detected by single-photon emission computed tomography (SPECT) imaging. The tracer binds very specifically to dopamine transporter sites on the neurons that are lost to Parkinson’s disease, allowing scientists to detect alterations in dopamine transport — a hallmark event in the disease’s development.

Working as a kind of enrichment biomarker for early stages of Parkinson’s disease, the radioactive tracer helps to differentially diagnose between essential tremor and other parkinsonian disorders, such as progressive supranuclear palsy or multiple system atrophy, and Parkinson’s “subjects with high likelihood of progressing in clinical motor disability.”

The tracer has been available in the European Union since 2000 with the brand name DaTSCANTM, and in the United States since 2011 as DaTscan. In 2015, the U.S. Food and Drug Administration issued a letter of support for the use of this imaging biomarker as a “prognostic biomarker for enrichment in trials for Parkinson’s disease.”

“These brain scans in themselves are not new, but until now there has not been a clear consensus that they can and should be used to select participants for clinical trials,” Stephenson said.

“The use of these brain scans is already being included in new clinical trials at Biogen,” said Michael Ehlers, MD, PhD, executive vice president of research and development at Biogen. “We believe that this new approach will introduce greater efficiency in terms of cost and speed, while ensuring that the right patients are being included in our trials.”

Due to the progressive nature of Parkinson’s, the best approach to slow, stop, or reverse the disease would be by intervening as early as possible. But disease manifestations can be subtle in its early stages, complicating trial recruitment.

Previous reports suggest that up to 15 percent of patients taking part in trials of new Parkinson’s therapies may not be the best candidates to measure potential efficacy, because of scant change in their motor symptoms during the time-limited course of such studies. In its early stages, disease progression can be difficult to predict.

“Being able to rule out individuals who are unlikely to have Parkinson’s could be the difference between a successful trial and failure,” said David Dexter, PhD, a professor at Imperial College London and deputy research director of Parkinson’s UK. “This is a vital step forward in our mission to deliver, as quickly as possible, better treatments, and one day a cure, to people living with Parkinson’s.”

The post Imaging Tracer with Potential to Bolster Clinical Trials of Parkinson’s and Its Treatments Favored by EMA appeared first on Parkinson’s News Today.

Source: Parkinson's News Today

Ketamine Studied for Relief of Levodopa-associated Involuntary Movements

ketamine study

A Phase 1 trial will test the potential of ketamine — an analgesic medicine used for depression and pain — at reducing the uncontrollable, jerky movements that arise in Parkinson’s disease patients after long-term treatment with levopoda.

Levodopa, probably the most common treatment for Parkinson’s disease, is effective at improving the stiffness and slowness of movement that characterize the disease.

However, up to 40 percent of long-term users eventually experience dyskinesia, which is the uncontrollable and involuntary movements that may be restricted to certain parts of the body, such as head, arms or legs, or affect the whole body.

“The problem is levodopa works great for a few years — we call that the ‘honeymoon’ period — but then you start getting these side effects,” Scott Sherman, MD, PhD, a neurologist at the University of Arizona College of Medicine – Tucson, said in a press release.

The severity of dyskinesia varies among patients, with some experiencing small jerky movements and others being affected by strong, constant bursts. Unfortunately, these side effects go away only after a patient stops taking levodopa.

So, researchers at the University of Arizona will conduct a small Phase 1 clinical trial with 10 Parkinson’s patients to determine the potential of ketamine for rescuing levopoda-induced dyskinesia.

The trial follows earlier work by Sherman and Torsten Falk, PhD, the scientists leading the study. They were using ketamine to relieve pain in Parkinson’s disease patients when they noticed an unexpected effect — the treatment also reduced the patients’ uncontrolled movements. One patient was actually free of the jerky movements for several weeks.

The same results were seen in animal models, where treatment led to a significant reduction in abnormal involuntary movements. The reduction was sustained for three days, and 10 days passed before baseline involuntary movements returned.

Ketamine increases blood pressure, but may cause a sensation of “out-of-body” experience, also known as dissociation, Sherman said. “When people describe it, they have told me that they feel like they are in fish bowl,” said Sherman. Ketamine actually has been used as a psychedelic recreational drug, Sherman said, adding that researchers have established preventive measures and he is hopeful those side effects will not affect the clinical trial.

“We are going to monitor blood pressure closely to make sure it doesn’t get high,” Sherman said. “And we know at what dosage ketamine causes this disassociation; we expect that the dosage needed in Parkinson’s disease will stay well below that level.”

Parallel to the Phase 1 trial, researchers will undertake a rodent study to assess the mechanisms underlying the effects of ketamine in the brain.

“We want to find out exactly what ketamine is doing to have this effect,” Sherman added.

Positive results in both the human trial and the animal study could help researchers establish ketamine as a therapy for patients with Parkinson’s disease.

“Ketamine has been long overlooked. Now it could prove very useful for Parkinson’s patients,” Sherman said.

The Phase 1 human and the animal study are both supported by a $750,000 three-year grant from the Arizona Biomedical Research Commission.

The post Ketamine Studied for Relief of Levodopa-associated Involuntary Movements appeared first on Parkinson’s News Today.

Source: Parkinson's News Today