Q-and-A with 23andMe Parkinson’s Community Lead

FoxFeed Blog

Posted by  Maggie McGuire, March 25, 2015

Paul Cannon, PhD, leads the 23andMe Parkinson's Community.

Genetic testing company 23andMe made headlines recently with announcements first of a deal with pharmaceutical company Genentechand then of its own new Therapeutics Group.

The Michael J. Fox Foundation has a long-standing relationship with 23andMe, helping recruit members for its Parkinson’s Community study and collaborating on research projects such as our LRRK2 Cohort Consortium.

Paul Cannon, PhD, who leads the 23andMe Parkinson’s Community, spoke with us about the company’s recent news and what it means for Parkinson’s disease (PD) drug development.

MJFF: What can you tell us about the 23andMe partnership with Genentech?

Paul Cannon: The deal with Genentech is a collaboration to whole genome sequence approximately 3,000 individuals with Parkinson’s or with a first-degree relative with PD. (The ratio is yet to be determined.) It’s a unique opportunity to learn more about the genetics of people with Parkinson’s disease and hopefully identify novel targets and biological pathways.

MJFF: How can genomic sequencing lead to new targets and treatments?

PC: It’s obviously the start of a long process, but one of the principle aims is to discover new therapeutic targets for Parkinson’s disease and specifically for disease-modifying therapies. There are a number of interesting therapies in development, but we need more shots on goal.

Through whole genome sequencing, we’ll look for genetic variants such as small deletions or insertions that are difficult to detect with our present mapping-based approach. It’s a more thorough interrogation of the genome made feasible by the decreased cost of whole genome sequencing and the analysis methods that have come along hand-in-hand.

MJFF: What is the difference between genomic sequencing and what you get from the 23andMe spit test?

PC: In whole genome sequencing you’re interrogating the majority of a person’s genome [complete DNA sequence]: every position of the approximately 3 million base pairs that we have in our genome. The single nucleotide polymorphism [SNP pronounced SNIP] genotyping that 23andMe traditionally uses currently interrogates around 650,000 markers on the genome. Those are the mileposts, where sequencing looks at every section of the road.

MJFF: How can people with Parkinson’s disease get involved?

PC: For this study, we’ll be recruiting from the existing 23andMe Parkinson’s Community. We’re defining the genetic and clinical profiles that will give us the highest chance of success, and those individuals will be invited from the existing database.

That said, we encourage those not yet in the 23andMe Parkinson’s Community to join us. There will definitely be future projects; this won’t be our only effort.

MJFF: Speaking of other efforts, 23andMe recently launched its own Therapeutics Group. What can you tell us about the aims there?

PC: It’s very exciting to have the opportunity to work with an in-house team that is focused on development of therapeutics. We’ve obviously worked with commercial partners on drug discovery, and we’ll continue to do so. I’m hoping to work with them on potential projects for Parkinson’s research, but that’s still to be determined.

I can’t speak for them, but they’ll mine interesting data, presumably, and look for opportunities that pop out across the broad spectrum of diseases represented in 23andMe. They’re using human genetics to drive therapeutic discovery and to improve development of drugs by matching patients with the right drugs through the use of genetics.

MJFF: Thanks for your time, Paul. Anything else you want our audience to know?

PC: My pleasure. As a last note, I’d just say that we continue to look to work with partners across the Parkinson’s disease research community. There are opportunities for other collaborations and projects, and we’ll work together to continue to push forward Parkinson’s research, ultimately for a cure.

Learn more about the 23andMe Parkinson’s Community.

https://www.michaeljfox.org/foundation/news-detail.php?and-with-23andme-parkinson-community-lead

Technology designed for aerospace could improve Parkinson's therapy

When Rice University chemist Matteo Pasquali set out to to create strong and conductive carbon nanotube fibers, he had aerospace applications in mind. But it turned out his microscopic fibers are also great at communicating with the brain, making them an ideal candidate for therapies that deal with neurological disorders such as Parkinson's disease. Pasquali said: "...once we [he and his team] had them in our hand, we realized that they had an unexpected property: They are really soft, much like a thread of silk. Their unique combination of strength, conductivity and softness makes them ideal for interfacing with the electrical function of the human body."

At the moment, hard metal electrodes are implanted into the brain for Parkinson's therapy (they deliver electrical signals to calm tremors), but they're not actually that compatible with the organ's soft tissues. These flexible fibers are more biocompatible -- they're also cheaper and maintain better electrical connection. Plus, the scientists' tests prove they cause little inflammation and are as stable as commercial platinum used on electrodes.

Rice U assistant professor Caleb Kemere who studies Parkinson's disease believes these fibers could lead to self-regulating treatment devices for patients. Those devices will be able to read signals from the brain, analyze the best amount of electrical stimulation needed to calm tremors on a case-by-case basis and automatically administer jolts of electricity. That's the gist of it anyway: if you want to read the team's study in greater detail, bust out your science jargon decoder and check out the paper on ACS Nano

http://www.engadget.com/2015/03/27/carbon-nanotubes-parkinsons-therapy/

Alzheimer’s Drug Shows Promise in Slowing Disease

FoxFeed Blog

Posted by  Maggie McGuire, March 23, 2015

On Friday morning our CEO sent around an email. Subject: This is big!

He was sharing news from pharmaceutical company Biogen Idec(renamed today as simply Biogen) around an Alzheimer’s drug in development with strong implications for Parkinson’s research. The drug — aducanumab (BIIB037) — showed safety and positive impact not only on clinical symptoms but also on brain imaging scans.

Alzheimer’s, like Parkinson’s, is a disease of protein clumps. In Alzheimer’s the protein amyloid-beta aggregates into what scientists call plaques. In Parkinson’s disease (PD), alpha-synuclein protein clumps to form Lewy bodies. Researchers believe these plaques and Lewy bodies harm brain cells.

Biogen compared BIIB037 to placebo in 166 people in the early stages of Alzheimer’s disease. Analysis showed no change in plaques among those given the placebo, but there was significant change in those who received the drug. In fact, those given more of the drug showed greater decrease in plaques and less decline in cognitive and functional abilities.

Big news, indeed. The company is planning a Phase III study with hopes to begin later this year.

What does this mean for people with Parkinson’s disease?

While not everyone with Parkinson’s develops dementia, some do. People with PD dementia often have amyloid plaques like those seen in Alzheimer’s, so a drug such as BIIB037 may benefit that population, though further testing would be necessary.

These findings are a win for Parkinson’s research, too, because BIIB037 is an antibody (disease fighters that help the body fend off harmful substances). Scientists are currently testing two antibody approaches against alpha-synuclein in clinical trials to slow Parkinson’s progression. The positive results from this Alzheimer’s study are a boost that this therapeutic strategy shows real promise.

This excitement comes with a caveat, though. Biogen has a biomarker tool to measure the impact of its drug; Alzheimer’s researchers can measure amyloid load in the brain through imaging capabilities. We don’t have such a tool for Parkinson’s research yet.

Our senior vice president of research programs Mark Frasier, PhD, is at the International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders in France, where Biogen shared its study results.

“I was at the presentation, and it was definitely impressive — both the changes on the biomarker scan but also the slowing of clinical progression. My takeaway from this entire meeting is how much we need better biomarkers of Parkinson’s disease,” he wrote in an email.

The Michael J. Fox Foundation is working urgently to validate Parkinson’s biomarkers. We’ve assembled a team to develop the technology to image the alpha-synuclein protein in the brain. And the MJFF-led Parkinson’s Progression Markers Initiative study is working toward measures of alpha-synuclein in blood or spinal fluid. Research toward these vital research tools is a top priority for the Foundation.

Learn more about PPMI and how biomarkers would speed testing of antibodies and other therapeutic approaches to slow Parkinson’s disease.

https://www.michaeljfox.org/foundation/news-detail.php?alzheimer-drug-shows-promise-in-slowing-disease&utm_source=social&utm_medium=facebook&utm_content=researchnews&utm_campaign=alzheimers-drug&s_src=researchnews&s_subsrc=alzheimers-drug#prclt-rvl1LfK9

New treatment could lead to a cure for Parkinson's disease

 Last updated: Thursday 26 March 2015 at 3am PST 15 Like12

Parkinson's disease, which took world fame after being diagnosed in various personalities such as actor Michael J. Fox, the heavyweight champion Muhammad Ali and the painter Salvador Dalí, could be very close to a cure, thanks to a Mexican researcher which managed to eliminate its neurological effects with an immunosuppressant.

Responsible for the scientific finding is Gabriela Caraveo Piso, researcher at the Whitehead Institute for Biomedical Research in the United States, who discovered that the role of calcium as an intracellular messenger can become lethal to brain cells when in high concentration.

Neurological diseases called synucleinopathies, such as Parkinson's, are characterized by the aggregation of alpha-synuclein protein. This action triggers a series of events such as the rise in intracellular calcium leading to over-activation of the enzyme calcineuria. This in turn removes phosphates (intracellular communication paths) to alter their functions and kill cells.

Gabriela Caraveo, a biologist graduated from the National Autonomous University of Mexico (UNAM), sought to nip this problem, after performing a series of analyzes in yeast, worms, and neurons of mice, found that by reducing the levels of activation of calcineurin, without eliminating it completely, the cells survived.

By modifying the activation of calcineurin contact with NFAT protein is cut out, and the communication to actin cytoskeletal rearrangements is redirected, which is responsible for cell morphology, thereby reducing failure in the motor function in animal models of Parkinson said the Mexican, who works in the lab of Susan Lindquist in the city of Cambridge, Massachusetts

To achieve adequate toxicity reduction the drug tacrolimus was used, which is administered clinically in newly transplanted patients to prevent organ rejection by the immune system.

Because calcineurin is also highly expressed in brain, this immunosuppressant that can cross the blood brain barrier is able to reduce the activation of calcineurin in the brain reducing the toxic symptoms of the disease. But it is important to adjust the dosage, because too much of it completely eliminates the activation of calcineurin preventing stimulation of protective pathways like the cytoskeleton leading to cell death.

"The dosage of the drug, also called FK506, I propose is well below the level of the immunosuppressants, which allows my work to have immediate treatment of neurological diseases characterized by the aggregation of alpha-synuclein as therapeutic implications as the Parkinson's disease," explained the specialist in neurosciences.

In healthy people, cells achieve to regulate the amount of intracellular calcium, the problem is when there are neurological diseases such as Parkinson's disease, the element is accumulated, becomes toxic and kills many neurons including dopaminergic neurons, responsible for implementing the motor functions.

According to preclinical results with tacrolimus pathologies associated to Parkinson's disease decreased in rodent models. The next step is to start human trials to test its effectiveness and safety as an alternative treatment that could even act as a cure.

http://www.medicalnewstoday.com/releases/291476.php?tw

Parkinson's Biomarker Initiative Expands Genetic Study

SOURCE The Michael J. Fox Foundation

PPMI now recruiting individuals with genetic mutation linked to Gaucher disease

NEW YORK, March 24, 2015 /PRNewswire-USNewswire/ -- The Parkinson's Progression Markers Initiative (PPMI), a large-scale biomarker study sponsored by The Michael J. Fox Foundation for Parkinson's Research (MJFF), is expanding to study individuals with a mutation of the GBA (glucosidase beta acid) gene. Participants will include people with or at increased risk to develop Parkinson's disease.  Researchers hope that a greater understanding of the biology and clinical features of these participants will lead to therapies benefiting all Parkinson's patients and ultimately provide strategies to prevent disease onset.

"Insights gleaned from volunteers with genetic mutations will help speed research toward new and improved Parkinson's therapies, benefitting the greater Parkinson's community," said Ken Marek, MD, principal investigator of PPMI and president and senior scientist at the Institute for Neurodegenerative Disorders in New Haven, Connecticut. 

Mutations in the GBA gene can cause Gaucher disease, a disorder where fatty substances accumulate in body cells. First linked to Parkinson's in 2008, these genetic mutations lower levels of an enzyme that helps break down proteins and lipids. In Parkinson's disease (PD) lower levels of this enzyme are associated with aggregation of the protein alpha-synuclein, the hallmark pathology of PD.

Genetics Provides Greater Understanding of Disease

Understanding the differences among people with and without PD who carry mutations such as in the GBA gene may help researchers understand what leads to disease onset and progression. In 2014 PPMI expanded to enroll individuals with a mutation of the LRRK2 or SNCA gene, the two targets of greatest interest in Parkinson's drug development.

One key tool missing from the development pipeline is an accurate way to measure progression of Parkinson's disease: a biomarker. Biomarkers would allow researchers to quickly and objectively measure a therapy's ability to slow, halt or reverse the Parkinson's process. PPMI is studying clinical and imaging data and biological samples of people with a genetic mutation to identify biomarkers, ultimately speeding clinical trials. In addition, when a drug targeting LRRK2, SNCA or GBA is ready for clinical testing, PPMI will have assembled a group of people with these mutations who stand ready to participate in studies. 

PPMI will enroll 125 people with the GBA mutation and who have Parkinson's and 125 people with the mutation who do not have Parkinson's. These participants will be followed for five years. By collecting data and samples over time from people who have not been diagnosed with the disease but who carry an associated genetic mutation, researchers can test for characteristics that may denote greater risk of disease onset or, conversely, protection from symptoms. 

Known genetic mutations currently account for only five to 10 percent of all Parkinson's cases. The vast majority of Parkinson's cases are idiopathic, meaning researchers do not know what causes the disease. However, study of individuals carrying PD-implicated genetic mutations may reveal disease traits that apply to all PD patients. The PPMI genetic cohort will expand understanding of the pathogenesis of both genetic and idiopathic Parkinson's disease.

Interested individuals can visit www.michaeljfox.org/ppmi/genetics. Similar to the LRRK2 mutation, the GBA mutation accounts for a greater number of PD cases among certain ethnic populations and families, notably those of Ashkenazi (Eastern European) Jewish descent. PPMI is particularly interested in testing individuals of this background who have Parkinson's or a close relative with the disease. 

PPMI: The Search for Parkinson's Biomarkers

Biomarkers - such as cholesterol level for heart disease - are substances, processes or characteristics of the body that indicate disease risk, onset and/or progression. They aid in diagnosis and disease management and help researchers stratify for clinical trials and test new drugs faster by measuring biological changes rather than waiting for clinical improvement. There are no validated biomarkers for Parkinson's disease, a reality researchers are hoping to change with PPMI.

Launched in 2010, PPMI is a longitudinal clinical study that collects standardized clinical, imaging and biologic data. Now taking place at 33 clinical sites around the world, the study completed initial enrollment of 423 recently diagnosed Parkinson's patients and 196 controls in April 2013. Since then, the study has expanded to include cohorts of individuals at increased risk of developing Parkinson's disease. Risk factors under study include genetics, REM sleep behavior disorder and smell loss. (Enrollment of the smell loss cohort was completed earlier this year.)

"By studying multiple cohorts, we're covering all bases to find and validate these biomarkers," said MJFF CEO Todd Sherer, PhD. "Expanding PPMI to include another genetic cohort allows science to push forward toward better therapies for people living with Parkinson's today and for those who may be at risk in the future." 

About The Michael J. Fox Foundation for Parkinson's Research As the world's largest nonprofit funder of Parkinson's research, The Michael J. Fox Foundation is dedicated to accelerating a cure for Parkinson's disease and improved therapies for those living with the condition today. The Foundation pursues its goals through an aggressively funded, highly targeted research program coupled with active global engagement of scientists, Parkinson's patients, business leaders, clinical trial participants, donors and volunteers.  In addition to funding more than $450 million in research to date, the Foundation has fundamentally altered the trajectory of progress toward a cure. Operating at the hub of worldwide Parkinson's research, the Foundation forges groundbreaking collaborations with industry leaders, academic scientists and government research funders; increases the flow of participants into Parkinson's disease clinical trials with its online tool, Fox Trial Finder; promotes Parkinson's awareness through high-profile advocacy, events and outreach; and coordinates the grassroots involvement of thousands of Team Fox members around the world. 

 http://health.einnews.com/article/256452174/CuekJjsDjrrpx3GITo view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/parkinsons-biomarker-initiative-expands-genetic-study-300054418.html

Results announced from Phase 1 single ascending dose study of PRX002, a monoclonal antibody for the potential treatment of Parkinson's disease

Last updated: Tuesday 24 March 2015 at 2am PST

Prothena Corporation plc, a late-stage clinical biotechnology company focused on the discovery, development and commercialization of novel protein immunotherapy programs, has announced positive results from a Phase 1 single ascending dose study of PRX002, a monoclonal antibody for the potential treatment of Parkinson's disease and other related synucleinopathies. PRX002 is the focus of a worldwide collaboration between Prothena and Roche.

PRX002 was safe and well-tolerated, meeting the primary objective of the study. Further, results from this study showed that administration of PRX002 leads to mean reduction of free serum alpha-synuclein levels of up to 96%. These overall results were highly statistically significant (p<0.00001). Reduction of free serum alpha-synuclein, a protein potentially involved in the onset and progression of Parkinson's disease and the target of PRX002, was shown to be robust, rapid and dose-dependent after just a single dose.

"There is genetic and pathological evidence that supports a causal role of alpha-synuclein in Parkinson's disease," said Todd Sherer, PhD, CEO of the Michael J. Fox Foundation for Parkinson's Research. "We applaud Prothena and Roche for their pioneering work in developing a potentially disease-modifying therapy for this progressive neurodegenerative disease that affects millions worldwide."

The Phase 1 double-blind, placebo-controlled, single ascending dose study enrolled 40 healthy volunteers. All volunteers enrolled were randomized 3:1 into five escalating dose cohorts (0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg or 30 mg/kg) to receive either PRX002 or placebo. No hypersensitivity reactions or drug-related serious adverse events were reported. PRX002 demonstrated favorable pharmacokinetic properties, supporting the current dosing frequency in the on-going Phase 1 multiple ascending dose study in patients with Parkinson's disease. There were no treatment emergent adverse events (TEAEs) in greater than 10% of subjects. The only TEAEs in greater than 5% of subjects were vessel puncture site pain, headache and viral infection. All PRX002-related adverse events were mild and no dose limiting toxicities were observed.

"We are extremely pleased with the results of the Phase 1 single ascending dose study as the mean reduction of free serum alpha-synuclein of up to 96% demonstrates the pharmacodynamic effects of PRX002," commented Gene Kinney, PhD, Chief Scientific Officer and Head of Research and Development at Prothena. "Importantly and for the first time in humans, we demonstrated that this robust, rapid and dose-dependent reduction of free serum alpha-synuclein was safe and well-tolerated. Thus, this approach may translate into a clinically meaningful delay or reversal of disease progression in patients with Parkinson's disease. We look forward to building upon these data with results from the on-going, multiple ascending dose study in patients with Parkinson's disease expected in the first half of 2016, where we will also be measuring levels of PRX002 in the cerebrospinal fluid and assessing additional biochemical, imaging and clinical biomarker endpoints. Separately, we are excited to co-host a symposium with Roche on March 21 at the 12th International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders (AD/PD™ 2015) to continue to raise awareness of the role of alpha-synuclein as a target for Parkinson's disease."

"The results of the PRX002 study exemplify Prothena's deep domain expertise to develop novel disease-modifying protein immunotherapies with unique specificities to their targets," stated Dale Schenk, PhD, President and Chief Executive Officer of Prothena. "Prothena's consistent ability to develop targeted potential therapeutics has resulted in a strong and promising pipeline to transform patient's lives, with NEOD001 in Phase 3 clinical studies for the treatment of AL amyloidosis, PRX002 continuing in a Phase 1 multiple ascending dose study in patients with Parkinson's disease and PRX003 ready to begin clinical studies for the treatment of psoriasis and potentially other inflammatory diseases."

In December 2013, Prothena and Roche entered into a worldwide collaboration to develop and commercialize antibodies that target alpha-synuclein, including PRX002. To date, Prothena has received $45 million of the potential $600 million in total milestones through its collaboration with Roche. Prothena has an option to co-promote PRX002 in the U.S., where the companies share all profits, as well as development and commercialization costs, on a 30/70 basis (30% Prothena and 70% Roche). Outside the U.S., Roche will have sole responsibility for developing and commercializing PRX002 and will pay Prothena up to double-digit royalties on net sales.

Adapted by MNT from original media release

http://www.medicalnewstoday.com/releases/291315.php?tw