Michael J Fox Foundation CEO Todd Sherer analyses the development of Parkinson’s treatment in a piece for US journal the ‘Scientific American’, published to mark 200 years since the condition’s discovery
The Michael J Fox Foundation’s CEO, Todd Sherer, has applauded the recent developments in Parkinson’s treatments, in a recent article for the Scientific American Blog Network.
The Parkinson’s campaigner, who has been with the Foundation since 2004, wrote: “I can say with confidence that the Parkinson’s disease field has made greater progress over the past two decades than in the two centuries that came before.”
“The field of genetics research has opened doors to a new understanding of the disease and greatly increased opportunities to slow, stop or even reverse the progression.”
In the online piece, published to mark 200 years since Parkinson’s discovery, Sherer highlighted improvements in administering treatment.
“New hypotheses have yielded evidence that the side effects of treatment may be lessened by changing how we deliver it – leading to the development of sin patches, inhalers and other devices that could improve patient’s quality of life.”
What would Dr James Parkinson think?
Sherer pondered the reaction that Dr James Parkinson might have had to these developments. Despite some of the more recent breakthroughs, Sherer says there is a lack of advancement in some areas, which would disappoint the pioneering surgeon.
“He’d likely be surprised to learn that doctors continue to diagnose Parkinson’s disease much in the same way he did in his day.
“There is no objective test or biomarker to predict, prevent or diagnose Parkinson’s, nor to conclusively track its progression over time.”
Celebrity campaigners
Sherer argues that developments in Parkinson’s medication can be attributed to the fact the community has become more engaged through the high-profile campaigners that have helped drive the movement.
“Inspired to action by vocal advocates such as Muhammad Ali and Michael J Fox, this community has joined forces so that all key payers – industry, government, researchers and non-profit groups – are now at the table alongside patients,” Sherer continued.
Sherer views this as a big improvement on the situation within the Parkinson’s community compared to 15 years ago. He says that back then the industry had become stagnant, and this had a negative effect on the development of treatments.
“The Parkinson’s drug pipeline was stalled, stem cells hadn’t panned out as the silver bullet many had hoped for, and little else was in the R & D (research and development) pipeline,” he added.
Moving forward
Despite many positives, Sherer refused to celebrate and instead reaffirmed his commitment to achieving the Foundation’s ultimate ambition.
“Our goal is to cure Parkinson’s, and with the participation of a robust and empowered community, we’ve never been closer.
“That’s because, as Michael J Fox would say, ‘The only things that’s incurable is our optimism.’”
The Michael J Fox Foundation was launched in 2000 with the aim of finding a cure for Parkinson’s disease. To date the Foundation has raised more than $700 million for Parkinson’s research.
Shakir Husain MD, DM (Neurology), Fellowship, Interventional Neuroradiology, Max Healthcare
Neurological disorders don't receive the attention they deserve. They get overshadowed by cancers and heart disease, even though they affect millions worldwide. These are the diseases of the central and peripheral nervous system affecting the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscles; and the disorders include epilepsy, alzheimer's disease, dementia, stroke, migraine among other headache disorders, along with multiple sclerosis, Parkinson's disease.
According to WHO, more than six million people die of stroke each year, over 50 million have epilepsy, 47.5 million people have dementia (Alzheimer's disease is the most common cause of dementia) and the prevalence of migraine is more than 10 per cent worldwide.
Compared to other therapeutic fields, neurological diseases are under-researched. However, thanks to the revolution in our understanding of the human genome, the grasp over the way the brain functions, and also the overwhelming complexity of illnesses that afflict the brain, is getting better every day. The fact that the need is so dire is making more scientists and companies dip their hands into the fresh science.
For example, 'Humanity' based in Cambridge is one such startup working in the field. They are using yeast, the microbes to study how misfolded proteins in the brain cause Alzheimer's, Lou Gehrig's disease and Parkinson's, and to create drugs based on that knowledge.
The industry is in midst of a dramatic reversal, with investors willing to pour money into firms that are developing drugs for psychiatric illnesses. Looking at the ongoing work, it seems that new medicines for severe depression, psychosis and schizophrenia could reach the market within the next few years.
Transformational work is already underway. For example, in 2004 researchers at the National Institutes of Health found out that a brain receptor called N-methyl-D-aspartate (NMDA), which is key to forming memories, was also involved in depression. Around the same time, a researcher at Yale found that ketamine, a widely used anesthetic, can block NMDA.
Extensive work is on to translate this knowledge into an effective drug. A nose-spray derivative of the drug is now entering late-stage trials; a pill is also being worked on. Similarly, an experimental drug, Sage-547, that blocks haywire electrical signals from jumping across nerve synapses in the brain and central nervous system, is being viewed as a great hope for controlling seizures in people.
However, all these are just a start to the changes scientists and pharma companies hope to bring about in the way we battle brain related disease. The intent is to end the hit-and-miss approach that is generally followed while prescribing medicines for similar conditions, and to move to a system that is based on what is biologically wrong with the patient.
May 13, 2017 Carole Stephen Smith, Special to The Desert Sun
The impressive Heckmann estate on Clancy Lane, owned by Dick and Wendy Heckmann was the site of a fundraiser for the Parkinson's Resource Organization (PRO) headed by Jo Rozen. She and radio personality Dan Ball pulled it together in just 40 days and drew over 350 people.
Rosen spoke passionately about her life's cause to find a cure for this devastating disease. One youthful guest, whose disease is now in its 14th year, spoke haltingly but bravely about what the organization has done for her and her care-taker family, both financially and emotionally.
There was not a dry eye in the entire place including Dan Ball who had to bounce back to the stage as MC still wiping away his tears. Ball's comedy and professionalism was clearly the highlight of the evening. He has now teamed up with Rozen as the Parkinson's director of development. For this event, Ball was accompanied by his mother and other supporters.
The evening's huge buffet was created by Lulu's with dessert by Brandini Toffee and Nothing Bundt Cakes.
Other features were strolling models in beautiful fashions, a photo booth, pin ball machines, a comedian and a DJ playing music throughout the event.
One of the many volunteers said she volunteered for these events because of Jo Rozen's dedication which she finds inspiring.
For more information phone 760-773-5628 or visit ParkinsonsResource.org.
Hope is different from optimism. Hope, to me, is the product of knowledge and the projection of where the knowledge can take us.” — Christopher Reeve
The open road has long symbolized the liberating power of possibility, an invitation to escape one’s current bonds of circumstance and journey to a new perspective or, perhaps, new reality. It’s a metaphor that became far more real during the first running of the Drive Toward a Cure road rally—an automotive adventure organized to accelerate fundraising and awareness for the fight against Parkinson’s disease.
Held in California, from April 28 through 30, the event drew a field of car enthusiasts, medical professionals, and patients—a disparate team of motorists fueled by each other’s spirit of altruism and adventure.
“I think the greatest challenge for me was holding onto the belief that folks would truly believe in the vision,” says Drive Toward a Cure’s founder Deb Pollack, who lost her own mother to the disease. “Knowing that my mom would have turned 90 this year and that she has now been gone for a decade was my inspiration.” Despite the worthy cause, however, filling the rally’s roster was a concern. “I was pretty scared that once we planned it all, no one would register,” she admits. “But when our very first entrant happened to have Parkinson’s and was bringing his 1960 Porsche 356B Super 90, my very favorite vintage car ever, there was no way I was going to disappoint him.”
The early registrant was former vintage racer Dick Cupp, and it soon became clear that disappointment would be diametric to the response Pollack received, especially when Carolee Barlow, the chief executive officer of the Parkinson’s Institute and Clinical Center, added her name to the list. By the time the friendly competition commenced, 36 cars were lined up for staggered starts at opposite ends of the state.
Along with a pair of 1960 Porsche 356s, a few of the classic standouts included a 1960 Bentley Continental Flying Spur, a 1961 Maserati 3500 Spider, a 1962 Jaguar E-Type, a 1964 Daimler SP250, and a 1966 Sunbeam Tiger Mk I. Among the eye-catching contemporary cars gathered were a 2007 Ferrari F430 Spider, a 2017 McLaren 570 GT, a 2017 Acura NSX, and a 2016 rear-wheel-drive Lamborghini Huracán.
The majority motored off Friday morning from the Petersen Automotive Museum in Los Angeles. Prior to departure, participants were treated to a private tour of the facility’s famed Vault—a repository of rare vehicles generally not on display—and new Ferrari retrospective. Concurrently, a northern sortie set off from the Blackhawk Automotive Museum in Danville, but with the same destination—central California’s bucolic and burgeoning wine-growing region of Paso Robles.
I had the privilege of joining the ranks of the southern collection while piloting a 2017 Maserati Quatrroporte S Q4. Donated to me for the week from Maserati North America, the 404 hp sedan can cover zero to 60 mph in 4.8 seconds on its way to 176 mph. The Quattroporte’s performance metrics were made more fun by the fact that my 86-year-old father was in the passenger seat as navigator—a man who is convinced that speeds in excess of 65 mph compromise the structural integrity of not just the car, but the human body itself.
Our roughly 260-mile route eschewed high-traffic highways and favored instead the paved ribbons that serpentine through the scenic canyons of Malibu, the mountains behind Santa Barbara, and the vineyards of the Santa Ynez Valley, all the while flanked by a landscape made verdant by a wealth of winter storms. Rendezvous points on the first day included the Mullin Automotive Museum in Oxnard to view its collection of Le Mans racers and current Citroën exhibit, as well as lunch in the Danish-themed town of Solvang at the Hotel Corque’s Root 246 restaurant.
Before parking it in Paso Robles, entrants had an opportunity to test their mettle on a closed skills course where the winning performance was delivered by Jeff Ehoodin, formerly with Ferrari, who, surprisingly, took the top time in a Subaru SUV—a David against a fleet of Goliaths.
The evening ended with a dinner hosted by the Allegretto Vineyard Resort, our lodging for the weekend. With both car contingencies finally together, the meal concluded with a member from each team introducing themselves and sharing what drew them to the drive, including a physician whose very first patient in practice was none other than the legendary Carroll Shelby.
“Listening to those that really appreciated supporting the cause, and especially the few there that had Parkinson’s themselves, really touched my heart and let me know we were on the right pathway,” says Pollack. “Drive Toward a Cure was fostering hope, and that, to me, made it all worthwhile.”
Saturday’s focus was on exploring the beautiful backroads that track through the surrounding terroir, a distinct blend of climate, geology, and geography responsible for more than 300 wineries. After the 135-mile morning session and a repast of French cuisine at Bistro Laurent in town, some participants took another 101-mile tour. The majority, however, chose to taste the local fruit of the vine or recline back at the resort, an option my navigator and I took full advantage of before being shuttled to the closing culinary experience and silent auction at Adelaida Vineyards and Winery. There, we were educated on the advances being made against Parkinson’s and why there is reason for optimism.
“This year will mark the first time that we will have at least one, and possibly two different disease-halting therapies available to patients who enroll in our clinical trials,” explains Barlow about the progress being made at the Parkinson’s Institute and Clinical Center. “We have been working toward this goal for almost 30 years—this is the critical step and we are finally here.”
Departing for home after Sunday’s farewell brunch at Eberle Winery, I looked over at my father (pictured above), grateful to still have him around and to be able share moments that he would later confess were some of the most memorable of his life—a sentiment tempered by the fact that he is getting a bit forgetful. And though not currently impacted by Parkinson’s personally, I am indebted to Pollack and her team for providing this son with such a gift, one that will be paid forward until the disease is defeated.
The three-day rally raised roughly $25,000 to benefit the Michael J. Fox Foundation and the Parkinson’s Institute and Clinical Center. The non-profit Drive Toward a Cure organization is also in the process of mapping out more philanthropic road trips for the future, including the Great Southern Adventure scheduled for September 26 through 29. (drivetowardacure.org)
Summary: Researchers have identified a potential neuroimaging predictor for dementia that highlights brain structural changes that may occur years before people even notice memory problems.
Source: Baycrest Center for Geriatric Care.
Within these older adults, researchers also found evidence of less brain tissue in the same subregion of the brain where Alzheimer’s disease originates (the anterolateral entorhinal cortex located in the brain’s temporal lobe). NeuroscienceNews.com image is for illustrative purposes only.
University of Toronto and Baycrest Rotman Research Institute (RRI) scientists have discovered a potential brain imaging predictor for dementia, which illustrates that changes to the brain’s structure may occur years prior to a diagnosis, even before individuals notice their own memory problems.
The joint study, published in the Neurobiology of Aging on May 8, looked at older adults who are living in the Toronto community without assistance and who were unaware of any major memory problems, but scored below the normal benchmark on a dementia screening test.
Within these older adults, researchers also found evidence of less brain tissue in the same subregion of the brain where Alzheimer’s disease originates (the anterolateral entorhinal cortex located in the brain’s temporal lobe).
This U of T-Baycrest study is the first to measure this particular brain subregion in older adults who do not have a dementia diagnosis or memory problems that affect their day-to-day routine. It is also the first study to demonstrate that performance on the Montreal Cognitive Assessment (MoCA) dementia screening test is linked to the volume (size) of this subregion, along with other brain regions affected early in the course of Alzheimer’s disease.
“This work is an important first step in determining a procedure to identify older adults living independently at home without memory complaints who are at risk for dementia,” says Dr. Morgan Barense of U of T’s Department of Psychology and senior author on the study.
The team studied 40 adults between the ages of 59 and 81 who live independently (or with a spouse) at home. All participants were tested on the MoCA. Those scoring below 26 – a score that indicates a potential problem in memory and thinking skills and suggests further dementia screening is needed – were compared to those scoring 26 and above.
“The early detection of these at-risk individuals has the potential to facilitate drug developments or other therapeutic interventions for Alzheimer’s disease,” says Dr. Rosanna Olsen, first author on the study, RRI scientist and assistant professor in U of T’s Department of Psychology. “This research also adds to our basic understanding of aging and the early mechanisms of Alzheimer’s disease.” Scientists were able to reliably measure the volume of the anterolateral entorhinal cortex by using high-resolution brain scans that were collected for each participant.
The strongest volume differences were found in the exact regions of the brain in which Alzheimer’s disease originates. The researchers are planning a follow-up study to determine whether the individuals who demonstrated poor thinking and memory abilities and smaller brain volumes indeed go on to develop dementia.
“The MoCA is good at diagnosing mild cognitive impairment (MCI) (a condition that is likely to develop into Alzheimer’s) and we are seeing that it may identify MCI in people who are not aware of a decline in their memory and thinking skills,” said Dr. Barense.
Alzheimer’s disease is a devastating neurodegenerative illness with widespread personal, societal and economic consequences. Currently, 564,000 Canadians currently live with dementia and 1.1 million Canadians are affected by the disease, according to the Alzheimer Society of Canada. There are 25,000 new cases of dementia diagnosed every year in Canada and it costs $10.4 billion to care for those living with dementia.
“A key take-away from the study is that it highlights the utility of the MoCA test in identifying individuals who are at-risk for dementia,” said Dr. Olsen.
Adults who are 40+ and interested in testing their memory and attention prior to raising concerns with their doctor can consult Baycrest’s scientifically-validated, online brain health assessment tool, Cogniciti.
ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE
Funding: Research for this study was conducted with support from the Canadian Institutes of Health Research, the Canada Research Chairs program, the James S McDonnell Foundation, the Natural Sciences and Engineering Research Council, and an Early Researcher Award from the Ontario Government.
The research team included RRI senior scientist Dr. Jennifer Ryan, former RRI post-doctoral fellow, Dr. Maria D’Angelo, and graduate students, Lok-Kin Yeung, Alix Noly-Gandon, and research assistants, Arber Kacollja and Victoria Smith.
The delicate tissues that line our nasal passages form a barrier between the environment and our brain. However, current mouse brain dissection techniques usually toss aside this tissue, even though Heiko Braak, Ulm University, Germany, and other scientists consider it important in the pathogenesis of Parkinson’s disease (PD). To take a closer look at the nasal cavity, its vulnerability to infection, and α-synuclein expression there, scientists have developed a new technique that preserves the entire olfactory system of a mouse by keeping intact the head—nose, teeth, and eyes, the whole shebang. Researchers led by Michael Schlossmacher, Ottawa Hospital Research Institute, Canada, used this method to visualize high levels of Parkinson’s-associated proteins in olfactory neurons. They also traced an infection as it progressed throughout the olfactory system into the brain. They report that α-synuclein plays a protective role against harmful microbes. The current study stops short of linking nasal infection with changes in α-synuclein; however, the method opens the door to future studies on how microbes affect α-synuclein expression and metabolism. The results appeared online May 5 in the Journal of Neural Transmission.
“The strength of this technique is the ability to visualize connections of the brain that aren’t routinely studied in mouse models,” said first author Julianna Tomlinson.
Complete Picture. By placing slices of mouse head under the microscope, scientists can see extra-cranial structures such as the sinuses above the tongue (T) and their connections to the brain. [Tomlinson et al., 2017. J Neural Transm.]
Nasal Cavity.
A close-up of the ethmoid sinus and olfactory bulb.
[Tomlinson et al., 2017. J Neural Transm.]
The olfactory bulb, along with the gut, has been proposed as an initiation site for PD pathology (see Jul 2011 news; Braak et al., 2003; Del Tredici and Braak, 2016). Aggregates are found there decades before symptoms emerge. Some think that misfolded α-synuclein itself, or infectious agents or toxins from the environment that alter α-synuclein, could propagate trans-synaptically to the brain. This hypothesis has been difficult to study in rodents because the intricate nasal structures are typically destroyed when a brain is dissected and prepared for microscopic analysis.
Pervasive Protein.
Cells of the olfactory epithelium (OE) express
α-synuclein (brown) from their dendrites to their axons,
which bundle into a cranial nerve that passes through
the bonycribiform plate (CP) to the brain.
Tomlinson et al., 2017. J Neural Transm.]
To solve this problem, Tomlinson and colleagues developed a technique they call “holocranohistochemistry.” Instead of lifting the brain out of the skull, this method prepares the whole head—including the dura mater, upper portions of the cervical spinal cord, and venous and lymphatic structures. After anesthetizing and killing the mouse, and separating the head, the researchers soak it in formic acid to dissolve calcium from the bony structures. Once soft, they preserve it in wax and slice it for mounting on slides. Subsequent staining revealed the complex network of olfactory receptor neurons and their nerve bundles, and how they connect to the brain.
Importantly, staining with α-synuclein antibodies in newborn and aged mice revealed abundant expression in the olfactory system (see image above right). This was true both in wild-type mice and α-synuclein A53T mice that overexpress human α-synuclein with a mutation linked to early onset PD. In olfactory receptor neurons, the protein turned up throughout—from the cells’ dendrites stretching to the nasal airways, to their cell bodies that traverse the olfactory epithelium, and all the way down their axons, which bundle together to form cranial nerve I. Tomlinson also saw tau expressed in the same spots.
Infection Path.
A few days after a virus is inhaled from the nose to the ethmoid sinus (ES), researchers use anti-viral antibodies (brown) to monitor the virus in dendrites and cell bodies of olfactory receptor neurons, as well as their axon bundles (arrows). [Tomlinson et al., 2017. J Neural Transm.]
Further testing the model’s ability to visualize neurodegenerative disease pathology in olfactory nervous tissue, Tomlinson and colleagues prepared the TgCRND8 mouse model that overexpresses mutant human APP. Their olfactory system also harbored Aβ plaques. Together, the data suggest all three proteins are expressed in the olfactory system in commonly used mouse models and can be analyzed for their role in disease pathogenesis, Tomlinson told Alzforum.
The scientists then used holocranohistochemistry to trace an acute viral infection that started in the nose in newborn wild-type mice. Sacrificing mice at different time points up to 10 days after inoculation, the researchers documented the march of reovirus-T3D from olfactory receptor neurons to these cells’ nerve bundles (see image above left). At the same time, the activity of microglia, as measured by an antibody to the microglial marker Iba1, flared up in the olfactory bulb, and infiltrating macrophages fought off infection in the olfactory epithelium and cranial nerve I. In parallel, the infection traveled from the nose to the lungs, spreading systematically. The ultimate brain infection came from a mix of olfactory and systematic sources. Virus invaded various regions of the brain, including the thalamus, midbrain, and cortex (see images below).
Brain infection: Anti-reovirus-T3D antibody finds the virus expressed in cells of the thalamus (I), midbrain (J), and cerebellum (K). [Tomlinson et al., 2017. J Neural Transm.]
What was α-synuclein up to in those infected neurons? One clue came from a paper by David Beckham, University of Colorado School of Medicine, Denver. He and colleagues reported that α-synuclein protected mice against West Nile virus in the brain (see Beatman et al., 2015). When infected, primary neurons pumped out more α-synuclein, which seemed to dampen viral replication. Mice lacking α-synuclein ended up with more virus in the brain and were less likely to survive.
To see if α-synuclein played a similar anti-microbial role in their model, Tomlinson infected newborn mice with reovirus-T3D, which causes a fatal brain infection in young pups. Indeed, α-synuclein knockouts succumbed more quickly than wild-type mice. Moreover, adult α-synuclein knockout mice injected in their tail veins with Salmonella typhimurium bacteria had a higher bacterial load in their spleens after five days. These data suggest α-synuclein has an antimicrobial function in innate immunity, wrote the authors. While they did not examine whether the infections directly affected α-synuclein in the olfactory system, Tomlinson said she next plans to examine the impact of chronic infection on α-synuclein metabolism in the nervous systems of older mice.
“I find this very intriguing,” said Patrik Brundin, Van Andel Research Institute, Grand Rapids, Michigan. “There seems to be a link between foreign microbes, be they virus or bacteria, and the triggering of synucleinopathy.” It should spur a lot of interest in understanding how foreign microbes trigger a boost in α-synuclein, he said, especially given mounting evidence that microbes in the gut influence α-synucleinopathies as well (see Sampson et al., 2016; Apr 2017 news). Brundin added that the holocranohistochemistry technique is potentially valuable, especially for researchers interested in studying the olfactory epithelium.
The survival effect in the current study was smaller than the one in Beckham’s, which he attributed to the different mouse models used. It will be important in future studies to probe the mechanism of α-synuclein’s antimicrobial abilities, Beckham told Alzforum. Interestingly, Aβ has also been proposed to function as an anti-microbial protein (see May 2016 news). “These proteins may have evolved in part to recognize harmful microbes and orchestrate an immune response that prevents infection of the nervous system,” Beckham told Alzforum.
If α-synuclein protein is protective against harmful microbes, and if pathogens make an environmental contribution to PD, then the data may suggest a new interpretation of the low CSF α-synuclein levels typically seen in PD patients, Tomlinson said. Perhaps reduced α-synuclein levels predispose a person to infection, and subsequent dysregulation kicks off the disease process. In essence, low CSF α-synuclein could represent a risk factor for Parkinson’s. Many believe it’s the other way around—that the lower protein levels result from the PD process already underway in nerve cells. Researchers conducting trials on therapies that seek to reduce α-synuclein long-term, and indeed Aβ, might be well advised to monitor for infection as a possible side effect, the authors recommended.—Gwyneth Dickey Zakaib
Adamas Pharmaceuticals has entered into an agreement with HealthCare Royalty Partners (HCR) in an effort to get some quick cash so that it can continue development of its pipeline.
Under the terms of the agreement, Adamas will get $35 million upfront and then another $65 million when the Food and Drug Administration approves Parkinson's drug ADS-5102 and gives it orphan Drug exclusivity. The drug is currently under review and has a user fee action date of August 24.
Adamas will use the proceeds from the royalty deal to pay for general
expenses, as well as the commercialization of ADS-5102.
Dive Insight:
Adamas Pharmaceuticals currently has all its eggs in three baskets – its two marketed drugs Namenda XR (memantine extended-release capsules) and Namzaric (memantine/donepezil extended-release capsules) licensed from Forest Laboratories, part of Allergan, and ADS-5102 (amantadine extended-release capsules).
This much-needed cash isn't coming cheap; Adamas will pay 11% interest on the outstanding principal on a quarterly basis until it has paid back 200% of the principal. Interest and principal will be payable through a 12.5% royalty on the sales of ADS-5102, as well as up to $15 million annually of Adamas' royalties from Allergan from the sales of Namzaric until May 2020. The royalty rate on ADS-5102 would drop to 6.25% once the principal has been paid. On the flip side, the royalty rate increases to 22.5% in the event that Adamas doesn't keep up with payments.
In Adamas' Pharmaceuticals first quarter results, the company announced a net loss of $16.0 million, with an almost 40% increase in general and administrative expenses, including increased headcount for the hoped-for launch of ADS-5102.
"We are thrilled to partner with HCR in this transaction, providing us with the resources to advance our business and commercialize ADS-5102, which we believe will create significant and sustainable value for all Adamas stakeholders." said Gregory T. Went, chair and CEO of Adamas Pharmaceuticals.
Adamas' stock value swooped down and then up on the day its earnings results came up, closing stable, but has fallen 5% on the news of the HealthCare Royalty Partners deal.
Touted earlier this year as a potential acquisition target, if it gains Food and Drug Administration approval, ADS-5102 could be the first drug for Parkinson's patients with levodopa-induced dyskinesia.
Elto Pharma, a spinout from Amarantus BioPharma, is developing its Phase 2 drug eltoprazine, for a number of indications, including levodopa-induced dyskinesia in Parkinson's disease.
Adamas has one other drug in clinical development in its rather sparse pipeline, ADS-4101 (lacosamide), for the treatment of partial-onset seizures in epilepsy. This is a timed-release (chrono-synchronous) formulation of an existing drug, Vimpat, and has completed a Phase 1 trial.
Rep. Pete DeGraaf, a conservative Republican member of the House, said he would end his service in “several days,” leaving more than 18 months in an unexpired term. (2016 file photo/The Associated Press)
Mulvane Rep. Pete DeGraaf announced his decision Friday to resign from the Kansas Legislature due to complications of Parkinson’s disease.
DeGraaf, a conservative Republican member of the House, said he would end his service in “several days,” leaving more than 18 months in an unexpired term. A minister, he was elected a state representative in 2008.
“Today is the day that is filled with lots of emotions, ranging from a deep sense of gratitude and thanksgiving for the wonderful experience of serving with you in this House — the people’s House,” he said. “In spite of the current challenges that we now have, Kansas is a wonderful place to live, to work and to raise a family. There are many issues that still concern me, but I entrust those to you now.”
He said colleagues in the House had been a source of encouragement to him and his wife, Karen, as the incurable disease took a toll. He had complainedin 2015 to doctors about pain and being unusually tired, which resulted in the diagnosis.
“I don’t have jitters, like 30 percent of us don’t have jitters or shakes, and while I may look normal, and some of you may say I look great, that’s Pete on Parkinson’s medication. That’s Pete in public,” he said.
He’s used a makeshift bed in his Capitol office to conserve energy for work on committees dedicated to elections, higher education, veterans and information technology.
“I tell you these things not to make you feel sorry for me, but rather to help you understand that people with various kinds of disabilities may look normal, but we still need your patience, forbearance, mercy, forgiveness,” DeGraaf said.
Khalifa University holds exhibition to showcase solutions developed by students to help society
The projects that were developed were wide ranging covering a number of areas including health, clean energy
Abu Dhabi: Freshman engineering students at Khalifa University showcased their skills and talent at an exhibition hosted by the institution on Wednesday, with the students developing innovative projects intended to help society.
The exhibition saw the participation of 240 engineering students who were challenged to come up with ideas and solutions to community challenges. The projects that were developed were wide ranging covering a number of areas including health, clean energy and recycling.
One of the projects on display was the Smart Stethoscope, which saw the development of a device to help monitor breathing and heart rates to improve the diagnosis for pneumonia.
Smart stethoscope
“Our project is designed mainly for poor countries and hospitals that cannot afford the proper equipment to help diagnose patients. When you buy a stethoscope, you probably spend more than Dh200, and our goal is to provide a device that costs less,” said Kenan Al Aqeel, a Syrian student involved in designing the device.
“The device that we built has a sound detector sensor, and a covering with rubber material to get the vibration from the heart sounds. When the device gets the heart sound, it can start giving you the heart rate, thanks to a coding process we developed.
“So, for example, when we are monitoring the heart rate for one minute, it shows you the beats and after that you get the accurate heart rate, for instance, a measurement of 110 beats,” he added.
Al Aqeel said the device can be attached to the patient’s chest, and that their device should cost only Dh30, providing a big boost to poorer patients.
“The device provides a system that manages to monitor the breathing rate which can hopefully improve the diagnosis of pneumonia and save lives.
“The goal is to help poor people and provide a solution. In Africa, people sometimes use their bare hands to measure the heart beat, and this is not a very accurate way to measure the beats, it can lead to an insufficient analysis which doesn’t help with coming up with a suitable diagnosis,” he added.
Stopping tremor
Another innovative project on display was Tremor Free Me, a device intended to limit the tremors caused by Parkinson’s disease.
“The device took us around six weeks to make. It can predict the speed of the shakes caused by the tremors associated with Parkinson’s disease,” said Hassan Odeh from Jordan, and one of the team’s participating students.
“So if a person’s hands shake, the device detects this shake and sends a voltage to the motors and changes the frequency of the motors to match the person’s hand frequency. When the motor interacts with the shake of the hand, it causes a destructive interference which will cancel the shake of the hand.
“The device is very light, it can be worn as a bracelet or a strap, and as soon as they get a tremor, the device will be able to detect it and apply the opposite oscillations to cancel it,” he added.
Odeh said the device would be a benefit for people with Parkinson’s disease as it could limit their uncontrolled body movements.
“The range of a shake caused by Parkinson’s disease is between 3.5 to 7 hertz. The motor can vibrate in an opposite oscillation frequency which will cancel the shake of a person’s hand so they can write clearly without much shaking.
“The device may not fully reduce all of the shaking, but it can help minimise it to some degree,” Odeh added.
CHICAGO - The first drug using spherical nucleic acids to be systemically given to humans has been developed by Northwestern University scientists and approved by the Food and Drug Administration as an investigational new drug for an early-stage clinical trial in the deadly brain cancer glioblastoma multiforme.
A clinical trial has just been launched at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and Northwestern Medicine.
The new drug is able to cross the challenging blood-brain barrier to reach tumors in animals, where it turns down a critical cancer-causing gene. Now, the Phase 0 clinical trial will investigate the drug’s ability to reach tumors in humans.
The glioblastoma drug represents a revolutionary new class of drugs. The novel spherical nucleic acid platform it is based on can be applied to other types of neurological diseases, such as Alzheimer’s and Parkinson’s, by similarly turning down the genes that lead to those diseases.
It’s highly unusual for a drug to be developed in preclinical research at a university, shepherded through FDA approval as an investigational new drug and studied in a clinical trial — all within the same university and without funding from a pharmaceutical company. In most cases, a drug is developed and licensed to a pharmaceutical company.
“We want to get the drug to patients as quickly as possible,” said Jay Walsh, vice president for research at Northwestern. “We want to move the drug forward because there are patients with a disease with no current cure."
The drug, called NU-0129, will have to go through many more phases before it is approved for general use in a clinical environment.
“We know this drug works in mice. Now we need to know if it can cross the human blood-brain barrier and accumulate in the tumor of a human being,” said Alexander Stegh, an assistant professor of neurology at Northwestern University Feinberg School of Medicine.
Stegh developed the drug with Chad A. Mirkin, the George B. Rathmann Professor of Chemistry at the Weinberg College of Arts and Sciences and director of Northwestern’s International Institute for Nanotechnology (IIN).
“If the spherical nucleic acids cross the barrier and localize in the brain, the implications go beyond glioblastoma,” Mirkin said. “This would give us the ability to target diseases of the brain by targeting pathways that we know are associated with different diseases, including Huntington’s, Parkinson’s and Alzheimer’s diseases.”
The drug, which consists of short snippets of RNA densely arranged on the surface of spherical gold nanoparticles, changes the genetic makeup of the tumor cells and dampens their ability to divide. The drug targets the gene BCL2L12, which is involved in apoptosis, or programmed cell death. Mirkin and his group invented spherical nucleic acids, and Stegh identified the gene to target.
Glioblastoma patients are treated with chemotherapy, radiation and surgery, but there is no cure. The life expectancy for the estimated 30,000 people in the U.S. who are diagnosed with the aggressive brain cancer each year is 14 to 16 months.
“We desperately need an effective treatment for this deadly disease,” said Dr. Priya Kumthekar, an assistant professor of neurology and hematology-oncology at Feinberg and a Northwestern Medicine neuro-oncologist. Kumthekar is the lead investigator of the Northwestern trial, which will recruit six to eight glioblastoma patients.
The study will recruit individuals who have had regrowth of their tumors and are candidates for tumor removal. They will receive the drug intravenously prior to surgery. Following tumor removal, Kumthekar and her team will study the tumor’s drug content to determine how well the drug crossed the blood-brain barrier in patients.
“Based on animal studies, there is good penetration into the tumor,“ Kumthekar said. “We predict that will be the case here, too.”
“Northwestern is very focused on delivering better therapy to patients,” said Dr. Frank Giles, who serves as Northwestern University’s sponsor representative on the investigational new drug application and clinical study. “Applying new scientific knowledge is the best way to develop truly paradigm-changing novel therapies.”
Kumthekar, Stegh, Mirkin and Giles are members of the Lurie Cancer Center.
“This was a complex, meticulous process requiring intense collaboration across many facets and groups within the University and Northwestern Medicine,” noted Ann Adams, associate vice president for research at Northwestern and one of the quarterbacks who led the FDA application process with Giles and Caroline Ko, a research associate in the department of chemistry and chief scientific officer of the IIN.
Dr. Leon Platanias, director of the Lurie Cancer Center, said, “The technology of spherical nucleic acids used in this first-in-human study is very powerful and may result in new, more effective approaches for the treatment of brain tumors and possibly other tumors in the future.”
The birth of the drug: spherical nanoparticles meet genetics
Stegh and Mirkin have been collaborating since 2009 to tackle the difficult problem of developing better treatments for glioblastoma. They first came together through Northwestern’s Center of Cancer Nanotechnology Excellence, funded by the National Cancer Institute.
Mirkin had the perfect tool: spherical nucleic acids, new globular forms of DNA and RNA — rather than linear — which are nontoxic to humans. The nucleic acid sequence is designed to match the target gene.
Stegh had the gene: in 2007, he and colleagues identified the gene BCL2L12 as one that is overexpressed in glioblastoma tumors and related to glioblastoma’s resistance to conventional therapies.
How the therapeutic works
The therapeutic, because of its novel structure, is actively taken across the blood-brain barrier, allowing it to reach the brain tumor. Once inside cancer cells, the drug silences the disease-causing gene. The RNA’s programmed sequence acts as a dimmer switch, selectively impeding the cells from producing specific proteins related to the disease. The result is selective cancer cell death and reduced cell growth.
Key to the drug’s success is the nanostructure’s 3-D spherical shape and nucleic acid density. Normal (linear) nucleic acids cannot get into cells or cross the blood-brain barrier, but these spherical nucleic acids can. Strands of RNA attach to and surround a gold nanoparticle like a shell; the nucleic acids are densely packed and form a tiny sphere. The gold nanoparticle core is only 13 nanometers in diameter.
Pivotal animal study
In 2013, Mirkin and Stegh were the senior co-authors of an animal study published in Science Translational Medicine. Their research team was the first to demonstrate delivery of a drug by intravenous injection that turns off a critical cancer-causing gene in glioblastoma, reducing tumor progression and increasing survival rates significantly in mice with the deadly disease.
In mice with glioblastoma, approximately 1 percent of the injected dose accumulated in the intracranial brain tumor tissue. Interestingly, once in the brain, the spherical nucleic acids selectively accumulated in tumor tissue over normal brain tissue. This is likely due to the ability of nanoparticles to accumulate in tumor tissue because of leaky blood vessels created by the tumor.
The survival rate of the animals increased nearly 20 percent, and tumor size was reduced three to four fold, as compared to the control group.
Mirkin first developed the nanostructure platform used in this study at Northwestern in 1996. This new development targeting glioblastoma was the first realization that the nanostructures injected into an animal naturally find their target in the brain and can deliver an effective payload of therapeutics.
Mirkin also is a professor of medicine, chemical and biological engineering, biomedical engineering and materials science and engineering.
Editor’s note: Northwestern University and some of the researchers involved in the development of the drug have financial interests relative to the drug used in this research study. As a result of these interests, Northwestern University and/or some researchers could ultimately benefit financially from the outcomes of this research.
