Thanks to the PAA Jr. Board and other volunteers, the 2018 Alabama Parkinson Fighter Walk & 5K was a huge success! This years event included 350 participants and raised over…CLICK TO READ MORE
Called the Parkinson’s Progression Markers Initiative (PPMI), the MJFF-backed effort is an ongoing observational study of more than 1,300 volunteer participants both with and without Parkinson’s to validate biomarkers and, over time, identify disease risk factors. Participants undergo a battery of tests and assessments.
Biomarker discovery is critical in the quest for therapies that can slow or halt Parkinson’s progression. Specifically, it would allow for earlier diagnosis, better disease tracking, and more efficient therapy tests. Current treatments only temporarily ease symptoms.
To glean as much as possible from patient data, Blackfynn will lead the PPMI Advanced Analytics Core, established to analyze biomarker discovery. The firm has a data integration and analysis platform it uses to drive development of therapies, and advance translational research for neurological diseases.
“The goal of the Advanced Analytics Core is to accelerate our analysis of the comprehensive within-subject data collected through PPMI,” Kenneth Marek, PPMI principal investigator, said in a news release.
“By combining this rich, multimodal data with Blackfynn’s platform and data science expertise, we hope to uncover insights into the determinants of [Parkinson’s disease] progression that will lead to new therapies and improved quality of life for patients.”
The Blackfynn infrastructure incorporates a full complement of medical and scientific data to enable swift assessment of data correlations and complex data visualizations. PPMI scientists plan to use the platform to interpret data, develop verifiable hypotheses, and better collaborate with the goal of more targeted translational research.
“Our work with MJFF and the PPMI investigators will maximize the value of this important patient dataset and help drive novel discovery with the potential to lead to the development of effective therapies for patients with PD,” said Amanda Christini, president of Blackfynn.
“Blackfynn will enable a new lens through which discoveries can be made, by looking at all raw and metadata together, in context, to find new patterns that are otherwise obscured when data are in isolation.”
Citing an unwieldiness caused by an abundance of Parkinson’s-related biomarker information, an editorial in the journal The Lancet Neurology heralded the efficiencies of collaborative research. Particularly, it applauded the Accelerating Medicines Partnership for its efforts to find a Parkinson’s cure.
As for the PPMI, five-year results have already shown that clinical trials in patients with early-stage Parkinson’s may benefit from assessing markers of disease progression — namely, changes in the Movement Disorder Society (MDS)-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and dopamine transporter imaging.
Launched in 2010, PPMI is underway in the United States, Europe, Israel and Australia.
The MJFF is dedicated to finding a cure for Parkinson’s by funding research and ensuring the development of improved therapies for those living with the disease. It has funded more than $800 million in research to date.
The post MJFF and Blackfynn Collaborate on Parkinson’s Study to Discover Biomarkers appeared first on Parkinson’s News Today.
Our annual symposium draws PD patients, caregivers, and loved ones from all over Alabama to engage multiple thought leaders who are experts in Parkinson’s Disease research, treatment, care and other focus areas. Whether you’re a PD patient, caregiver, medical professional, advocate, or simply want know more about this complex disease – the Parkinson’s Symposium offers something for everyone.
This years event was Saturday, September 15 from 8:30AM to 2:00 PM at The Club (Ballroom) in Birmingham.
If you were unable to attend the 2018 Parkinson’s Symposium, we hope you’ll take a moment to review our media archive – speaker presentation materials and audio along with a photo gallery of all attendees and participants.
Parkinson’s Institute and Clinical Center and Retrotope have paired up to explore the therapeutic potential of the investigational agent RT001 in patients with progressive supranuclear palsy (PSP), a type of treatment-resistant Parkinson’s disease.
Under Retrotope’s expanded access program for RT001, the institute’s physicians started dosing two PSP patients with the investigational therapy. This pilot study is expected to provide information to help guide future randomized placebo-controlled trials in PSP.
“The Parkinson’s Institute and Clinical Center brings novel therapies for [Parkinson’s disease] to patients in need,” Carrolee Barlow, MD, PhD and CEO of the institute, said in a press release. “We look forward to working with Retrotope in evaluating the responses to this therapeutic candidate in these patients.”
RT001 belongs to a new therapy class called deuterated polyunsaturated fatty acids, or D-PUFAs, that protect mitochondria and cells from damage caused by oxidation of fat molecules, which often results in cell death that is a hallmark of numerous neurodegenerative diseases including Parkinson’s. Mitochondria provide energy and are known as the “powerhouses” of the cells. The investigational agent is an engineered, more stable form of linoleic acid that mimics the protective effects of the fatty molecule Omega-6.
RT001 is integrated in cell and mitochondria membranes and, as it is a stabilized fatty molecule, does not react with damaging free reactive oxygen elements — toxic compounds produced as a consequence of cellular oxidative stress — restoring membrane function and cellular health.
“The patients we treat with these fatal, degenerative diseases are willing to try therapies which appear safe and for which there is a mechanistic rationale that they may benefit from the treatment,” Barlow said. “Retrotope is a willing partner with a highly unique and well-studied approach to addressing neurodegenerative diseases.”
“The institute’s goal is to find a cure for Parkinson’s and Expanded Access programs like Retrotope’s are really at the forefront of generating hope for patients from novel therapies, and data for pharmaceutical companies to plan their drug trials,” she added.
The therapeutic potential of this investigational agent is being tested in patients with inherited Friedreich’s ataxia (FA) and infantile neuroaxonal dystrophy (INAD).
In addition, this new agent has been shown in preclinical studies to hold therapeutic potential in other illnesses where mitochondria function and induced cell death play a role, including Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis (ALS).
Preclinical data has shown that RT001 orally administered to mice with induced Parkinson’s disease could effectively improve the levels of dopamine by 2.5 times in the brain area most affected by the disease. In addition, the treatment effectively prevented brain cells’ degeneration in these animals.“Early results in clinical trials of RT001 and Expanded Access programs for a variety of neurodegenerative diseases have generated encouraging results along with a favorable safety profile,” said Peter G. Milner, MD and chief medical officer of Retrotope. “We look forward to providing updates on this and other studies in the coming months as we support patients and investigators exploring the utility of RT001 to block lipid peroxidation in a range of primary neurodegenerative diseases.”
The Linked Clinical Trials (LCT) Initiative, a repurposing program that aims to identify existing medicines which can slow the progression of Parkinson’s disease, has resulted in a growing number of clinical trials. The partnership’s history, purpose and activities are the focus of an article, “The Linked Clinical Trials Initiative (LCT) for Parkinson’s disease,” that recently appeared in the European Journal of Neuroscience.
The International Parkinson’s LCT Initiative was conceived in 2010 by Tom Isaacs, late president and co-founder of the London-based Cure Parkinson’s Trust (CPT), and Richard Wyse, the organization’s current director of research and development.
CPT decided to support preclinical and clinical studies of potential disease-modifying therapies (DMTs) and of medications approved for other illnesses in therapy repurposing trials. Symptomatic treatments were not explored, as they were already being extensively investigated in industry-sponsored studies.
The Committee to Identify Neuroprotective Agents for Parkinson’s program greatly influenced the launch of LCT. Initiated in 2003, the program assessed more than 20 potential Parkinson’s therapies. Several were selected to enter clinical trials, but none met their primary clinical goals.
Yet given the ensuing discovery of new disease mechanisms and therapeutic targets, as well as the growing notion that some of the first events in Parkinson’s development occur outside the brain, it seemed “very reasonable to revisit the concept of drug repurposing in [Parkinson’s],” researchers wrote.
LCT’s initial focus was to gain insight from key opinion leaders on appropriate medications to test for potential therapies in Phase 2 trials of Parkinson’s. If successful, these trials would lead to Phase 3 studies and market possible new therapies.
The goal was to have multiple parallel trials comparing different therapies with a similar protocol. Yet the need to for different placebos and durations of treatment, among other factors, made this impossible.
Patrik Brundin, MD, then working at Sweden’s Lund University, agreed to chair the LCT scientific committee. Isaacs and Wyse approached Brundin because of his contributions to the Parkinson’s field and deep understanding of clinical and basic science. Overall, the scientists involved in LCT felt that studies should look at impaired processes — such as neuroinflammation or energy metabolism — and favor compounds able to affect more than one such process. Also, as there was no DMT for Parkinson’s, the disease was an attractive target for therapy repurposing, an approach that can be significantly time- and cost effective to find new medications.
The effort included eight scientists, including Brundin. Another scientist, Jeffrey Conn, PhD, of Tennessee’s Vanderbilt University Medical Center, was a global expert in blood-brain barrier penetration and pharmacology. The blood-brain barrier is a semipermeable membrane that protects the brain from the outside environment. Penetrating this barrier and reaching the brain is critical in treating neurological diseases.
Three patients, including Isaacs, attended the first LCT meeting in 2012 at the Van Andel Research Institute in Grand Rapids, Michigan. Also present were representatives from the Michael J. Fox Foundation for Parkinson’s Research, the Parkinson’s Foundation, and Parkinson’s UK. Since then, patient participation has increased, providing immediate access to their perspectives and discussions on trial design and continuation, as well as compliance with specific therapies.
The first LCT meeting led
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.
People with inflammatory bowel disease (IBD), an umbrella name for disorders marked by prolonged inflammation of the digestive tract, are at a higher-than-usual risk for Parkinson’s disease, a review study involving 8.9 million IBD patients suggests.
The study, “The risk of Parkinson’s disease in inflammatory bowel disease: A systematic review and meta-analysis,” was published in the journal Digestive and Liver Disease.
Inflammatory bowel disease (IBD) is a term that includes two main disorders — ulcerative colitis and Crohn’s disease — and is characterized by an imbalanced immune response that triggers prolonged inflammation of the digestive tract.
Inflammation in ulcerative colitis is confined to the colon (large intestine), while in Crohn’s disease it can involve any part of the digestive system. But inflammation in Crohn’s is most common at the end of the ileum (the last section of the small intestine) or the colon.
Several studies have reported that some of the inflammatory pathways impaired in Parkinson’s are also found in IBD. Certain population-based studies have also reported an increased prevalence of Parkinson’s among IBD patients, but the link between both disorders remains controversial. Another follow-up study failed to confirm those initial findings.
Researchers in China conducted a meta-analysis of published literature focusing on Parkinson’s risk in IBD using two databases, PubMed and Embase, and including in their search the keywords “ulcerative colitis” and “Crohn’s disease.” For the meta-analysis, they included cohort or case-control studies with patients diagnosed with IBD, either ulcerative colitis and Crohn’s disease, and whose main outcome was Parkinson’s.
Out of an initial pool of 172 studies, four studies accounting for a total of more than 8.9 million patients were included in the meta-analysis. (A meta-analysis is a statistical technique used to summarize in a quantitative manner the findings of multiple studies.)
Performed in the United States, Denmark, Sweden and Taiwan, these four studies assessed the incidence rate of Parkinson’s in IBD patients, specifically those with Crohn’s and ulcerative colitis. Three had been conducted in 2018, and one in 2016.
“To our knowledge, this is the first MA [meta-analysis] to focus on the risk of PD [Parkinson’s] in IBD patients,” the research team wrote. “Despite the small number of studies included, the patient numbers were large due to the population-based nature of the included studies.”
Pooled results of all studies suggested that an IBD diagnosis was associated with a 41% increased risk of developing Parkinson’s.
Assessing the risk of ulcerative colitis and Crohn’s disease separately, researchers found that both disease subtypes were linked to a higher Parkinson’s risk compared with age- and sex-matched controls — Crohn’s patients had a 28% higher risk of Parkinson’s, and those with ulcerative colitis a 30% increased risk, the study reported.
Among the IBD patients, the risk for Parkinson’s was not affected by gender, with similar rates seen in male and female patients, or by age.
Overall, this meta-analysis “identified an increased risk of PD in IBD patients,” the reseachers wrote, which “remained significant when separately analysing CD [Crohn’s disease] and UC [ulcerative colitis] subgroups.”