Cell Therapy Could Improve Brain Function in Alzheimer’s

NEUROSCIENCE NEWS  MARCH 17, 2018
Source: Gladstone Institute.

Adding the Nav1.1 protein boosted the activity of interneurons and helped restore brain function in mouse models of Alzheimer’s disease, researchers report.

The findings could eventually lead to the development of new treatment options for patients with Alzheimer’s disease. NeuroscienceNews.com image is in the public domain.

Like a great orchestra, your brain relies on the perfect coordination of many elements to function properly. And if one of those elements is out of sync, it affects the entire ensemble. In Alzheimer’s disease, for instance, damage to specific neurons can alter brainwave rhythms and cause a loss of cognitive functions.

One type of neuron, called inhibitory interneuron, is particularly important for managing brain rhythms. It’s also the research focus of a laboratory led by Jorge Palop, PhD, assistant investigator at the Gladstone Institutes. In a study published in Neuron, Palop and his collaborators uncovered the therapeutic benefits of genetically improving these interneurons and transplanting them into the brain of a mouse model of Alzheimer’s disease.

Interneurons control complex networks between neurons, allowing them to send signals to one another in a harmonized way. You can think of inhibitory interneurons as orchestra conductors. They create rhythms in the brain to instruct the players–excitatory neurons–when to play and when to stop. An imbalance between these two types of neurons creates disharmony and is seen in multiple neurological and psychiatric disorders, including Alzheimer’s disease, epilepsy, schizophrenia, and autism.

A Brain without a Conductor

Palop’s previous studies showed that, in mouse models of Alzheimer’s, the inhibitory interneurons do not work properly. So, the rhythms that organize the excitatory cells are disturbed and fail to function harmoniously, causing an imbalance in brain networks. This, in turn, affects memory formation and can lead to epileptic activity, which is often observed in patients with Alzheimer’s disease.

His team found a way to reengineer inhibitory interneurons to improve their function. They showed that these enhanced interneurons, when transplanted into the abnormal brain of Alzheimer mice, can properly control the activity of excitatory cells and restore brain rhythms.

“We took advantage of the fact that transplanted interneurons can integrate remarkably well into new brain tissues, and that each interneuron can control thousands of excitatory neurons,” said Palop, who is also an assistant professor of neurology at the University of California, San Francisco. “These properties make interneurons a promising therapeutic target for cognitive disorders associated with brain rhythm abnormalities and epileptic activity.”

First, the scientists had to overcome a significant challenge. When they transplanted regular interneurons, they saw no beneficial effects, presumably because Alzheimer’s disease creates a toxic environment in the brain.

The researchers then genetically boosted the activity of inhibitory interneurons by adding a protein called Nav1.1. They discovered that the interneurons with enhanced function were able to overcome the toxic disease environment and restore brain function.

“These optimized neurons are like master conductors,” said Palop. “Even with a declining orchestra, they can restore the rhythms and harmony needed for cognitive functions.”

Conductors Engineered for Alzheimer’s Disease

The findings could eventually lead to the development of new treatment options for patients with Alzheimer’s disease.

“Besides the applications this cell engineering and transplantation approach may find in regenerative medicine, our findings support the broader concept that enhancing the function of interneurons can counteract key aspects of Alzheimer’s disease,” said Lennart Mucke, MD, director of the Gladstone Institute of Neurological Disease.

In addition to examining if the cell therapy could be translated from mice to humans, Palop and his team are working to identify potential drugs as an alternative way to enhance the function of inhibitory interneurons.

“Advancing our understanding of Alzheimer’s disease and identifying potential new treatment strategies are critical to addressing the escalating global health crisis,” said Elizabeth Edgerly, PhD, executive director of the Alzheimer’s Association, Northern California and Northern Nevada chapter. “We were proud to support Dr. Palop’s research and vision with an Investigator Initiated Research Grant award.” The Alzheimer’s Association, which funded part of the study, is the world’s largest nonprofit funder of Alzheimer’s research.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

The study’s first equal contribution authors are Magdalena Martinez-Losa, Tara Tracy, and Keran Ma. Other contributors include Laure Verret, Alexandra Clemente-Perez, Abdullah Khan, Inma Cobos, Kaitlyn Ho, Li Gan, Lennart Mucke, Manuel Alvarez-Dolado, and Jorge Palop.

Funding: The research at Gladstone was funded by the National Institutes of Health, the Alzheimer’s Association, and the S.D. Bechtel, Jr. Foundation.

Source: Julie Langelier – Gladstone Institute

Publisher: Organized by NeuroscienceNews.com.

Image Source: NeuroscienceNews.com image is in the public domain.

Original Research: Open access research in Neuron.

doi:10.1016/j.neuron.2018.02.029

Abstract

Nav1.1-Overexpressing Interneuron Transplants Restore Brain Rhythms and Cognition in a Mouse Model of Alzheimer’s Disease

Highlights

•Nav1.1-enhanced interneuron transplants reduce deficits in Alzheimer model

•Nav1.1-deficient interneuron transplants cause behavioral deficits in wild-type mice

•Nav1.1 elevation accelerates action potential kinetics in transplanted interneurons

•Molecular optimization of cell transplants is required for therapeutic benefits

Summary

Inhibitory interneurons regulate the oscillatory rhythms and network synchrony that are required for cognitive functions and disrupted in Alzheimer’s disease (AD). Network dysrhythmias in AD and multiple neuropsychiatric disorders are associated with hypofunction of Nav1.1, a voltage-gated sodium channel subunit predominantly expressed in interneurons. We show that Nav1.1-overexpressing, but not wild-type, interneuron transplants derived from the embryonic medial ganglionic eminence (MGE) enhance behavior-dependent gamma oscillatory activity, reduce network hypersynchrony, and improve cognitive functions in human amyloid precursor protein (hAPP)-transgenic mice, which simulate key aspects of AD. Increased Nav1.1 levels accelerated action potential kinetics of transplanted fast-spiking and non-fast-spiking interneurons. Nav1.1-deficient interneuron transplants were sufficient to cause behavioral abnormalities in wild-type mice. We conclude that the efficacy of interneuron transplantation and the function of transplanted cells in an AD-relevant context depend on their Nav1.1 levels. Disease-specific molecular optimization of cell transplants may be required to ensure therapeutic benefits in different conditions.

http://neurosciencenews.com/cell-transplant-alzheimers-8655/

Babies and Parkinson’s sufferers benefit from $2m gift

Saturday, 17 March 2018 -University of Auckland

Babies and Parkinson’s sufferers benefit from $2 million gift

A generous gift of $2 million from the Hugo Charitable Trust has been given to the University of Auckland to conduct research into growth restriction in babies and to help those with Parkinson’s disease.

Maryanne Green, the eldest daughter of Irish philanthropist and businessman the late Hugh Green - known in Ireland as Hugo, founded the Hugo Charitable Trust last year to continue Hugh’s philanthropic legacy and to give back to the people of New Zealand. Maryanne worked closely at Hugh’s side for over 25 years where she developed a deep understanding of Hugh’s philanthropic priorities and wishes.

“Hugh loved Ireland and New Zealand equally and he believed passionately that education was the key to a better New Zealand,” she said. “The Hugo Charitable Trust is committed to honouring Hugh’s life work and building on his legacy for the future benefit of New Zealand with new ideas, new ways and new directions for the future.”

The Hugo Charitable Trust has committed $1 million each to the Liggins Institute and the Auckland Bioengineering Institute (AB) at the University of Auckland to fund a research cluster comprising an emerging researcher, two PhD students, and research support over four years.

At the Liggins Institute, Associate Professor Katie Groom will lead a research cluster focussing on understanding the causes of preterm birth and fetal growth restriction.

Associate Professor Groom – a world leader in the area of diagnosis and therapy for growth-restricted babies – will undertake research into approaches to decrease preterm birth and into the best management of women who are at risk of it. She is also undertaking research into potential new therapies to promote growth of babies, including the use of sildenafil citrate (also known as Viagra) to improve blood flow to the placenta. 

At the Auckland Bioengineering Institute (ABI), Dr Daniel McCormick will carry out research into the new field of optogenetics, which uses light to manipulate neural activities in conditions where stimulation is required. It offers the prospect of treating life-time conditions such as Parkinson’s disease with a wireless implantable device. Dr McCormick’s team is assessing the viability of using custom-made wireless LED implantable devices to measure individual cellular response to light.

University of Auckland Vice-Chancellor, Professor Stuart McCutcheon, said that the University is dependent on the support of donors and philanthropists to enable it to continue with the world class research for which it is renowned.

“We need benefactors like the Hugo Charitable Trust. Without them we do not have the level of funding to keep the University world-class and delivering on our commitment not only to be New Zealand’s pre-eminent research-led institution, but one that makes a sustained contribution to global issues.

“The significant impact we are already making in areas that can affect the whole world are only possible through philanthropic support of individuals and organisations that have that same commitment,” he said.

The Vice-Chancellor says the research being funded by the donation is well-aligned with the aims of the University of Auckland Campaign For All Our Futures. This was established to support the University’s drive to address some the most complex issues facing the world.

http://www.scoop.co.nz/stories/GE1803/S00043/babies-and-parkinsons-sufferers-benefit-from-2m-gift.htm

The right time of year to dance an Irish jig

March 16, 2018  -  By Maddie Gehling 

PEORIA — Each year, March means the first day of spring and a bevy of St. Patrick’s Day deals at local bars and pubs. But for Erin Rockhold, the third month of the year doesn’t necessarily mean a pint of Guinness with corned beef and cabbage — it means jigs and traditional Irish music.

Rockhold owns the Isle of Erin Irish dance studio in Peoria, where she also serves as creative director. Naturally, March is the busiest time for her dancers.

“We put on a show, and I educate the people sitting in front of me what it’s like to be an Irish dancer,” Rockhold said.

The studio has grown since it opened eight years ago, and Rockhold now teaches a variety of Irish dance classes for students just beginning to learn, as well as those looking to compete at the national and international levels.

“I just love dancing — the feel of it, the music,” said Annaliese Springer, who has been dancing at Isle of Erin for more than five years. “It’s taught me so much, like hard work, effort, perseverance.”

Springer, 20, said Irish dance provides her with an emotional tie to her grandfather, who had Parkinson’s disease and passed away when she was younger.

“When I started Irish dance about five years ago, studies started coming out saying how we can use Irish dance for therapy for Parkinson’s,” Springer said. “I always think of my grandpa when I dance now. ... That therapy side of it is something I want to invest in in the future.”

Rockhold’s longtime friend and dance companion Angie Gin also helps teach lessons. She said she was influenced by the popular 1990s dance shows “Riverdance” and “Lord of the Dance” when she was growing up.

“I just enjoy it,” Gin said. “I didn’t want to give it up, I’m not going to give it up.”

One of Rockhold’s favorite aspects of Irish dance is the way she sees it empowering her young dancers — specifically the girls.

“I’m very body-positive and self-positive,” Rockhold said. “I compare all of the people I have at my dance studio to flowers. Just because a daisy, a sunflower and a rose look different, smell different, they bloom at different times of the year ... it doesn’t mean they’re not flowers and that they’re not beautiful.”

Jessi Guzman, 21, said people she meets often don’t believe Irish dance should be considered a sport. But she’s even more empowered when she has the chance to show them the skill and endurance it takes to be an Irish dancer.

“When I say I Irish dance, people think it’s weird,” Guzman said. “But when they see me Irish dance, they always say, ‘That’s so cool.’”

To Rockhold, the reward comes in being able to make what she loves accessible and fun for anyone in the central Illinois area.

“My mother cleaned toilets so she could afford for me to take Irish dance lessons,” Rockhold said. “That’s the main reason I teach Irish dance. My goal is to level the playing field for all those kids so those parents don’t have toilets to clean. ... Everyone should be allowed to dance if they want to.”

Dancers from the studio will perform in the St. Patrick’s Day parade in Downtown Peoria, which kicks off at 11 a.m. Saturday. Later that day, they will also perform at 2:30 p.m. at the St. Augustine Manor, 1301 NE Glendale Ave., as well as at 6 p.m. at the Fox Pub & Cafe, 7800 N. Sommer St.

Isle of Erin Irish dance studio is located at 1227 W. Glen Ave.

http://www.pjstar.com/news/20180316/right-time-of-year-to-dance-irish-jig

Teed to take Parkinson’s battle to D.C.

By John Hacker  March 16, 2018

A former Carthage City Council Member has returned to his home town with a new burden, or “gift” as he calls it, and a new purpose in life.

A former Carthage City Council Member has returned to his home town with a new burden, or “gift” as he calls it, and a new purpose in life.

T.J. Teed is a Sarcoxie native who lived in Carthage for eight years and served on the Carthage City Council for four years, from 2008-2012, before he moved to Northwest Arkansas for his job.

It was in Arkansas four years ago that his life took a dramatic turn.

“I had been experiencing some shaking and tremors in my right hand and we went back and forth to the doctor and I had been misdiagnosed several times on what everyone thought it was,” Teed said. “Finally I made a trip to Barnes Jewish Hospital in St. Louis and was able to see the movement disorder specialist there. I was there for about 15 minutes and they looked at me and said you have Parkinson’s Disease.“

Teed said his age was part of the problem when it came to getting an accurate diagnosis. Teed is 37 now, but he was 33 when he was searching for the cause of the tremors in his hand.

“A lot of doctors would look at me and say, you’re too young for Parkinson’s,” Teed said. “That wasn’t the case at all, anybody can get Parkinson’s. It typically runs in older people, but that’s the thing, I was young onset. I tell people I’m a 37 year old man in an 80-year-old’s body. Sometimes that’s the way it feels. I’m not able to be as active as I used to be. I get tired very quickly and wish I could run and play with my kiddos like I used to be able to do.“

Teed says he’s taking his diagnosis in stride and working to do what he can to help others and help find a cure. 

He’s a stay-at-home dad for his four kids, Jayden, 11; Abby, 9; Kaitlyn, 7; and Tyler, 4. His wife, Alyssa Teed works for Arvest Bank, that’s why the family moved to Arkansas six years ago.

Teed said Arvest worked with his wife to enable her to work from a Carthage bank so the family could move closer to loved ones who could help him when needed.

And next week he’s traveling to Washington, D.C., with the Michael J. Fox Foundation for Parkinson’s Research, a foundation created by the actor and comedian, Michael J. Fox, who was diagnosed with Parkinson’s at age 29. 

In a written release, the foundation said Teed and more than 300 other advocates will meet with members of Congress to “share their stories of the personal impact Parkinson’s disease (PD) has made on their lives and the lives of their loved ones. Delegates will educate lawmakers on the need for federal funding for research toward a cure for Parkinson’s, and policy support for those living with the disease.“

Teed is attending the 2018 Parkinson’s Policy Forum, an event supported by the Fox Foundation and nine other Parkinson’s organizations across the country.

“The 2018 Parkinson’s Policy Forum will feature two days of training, followed by one day of advocacy, congressional outreach and education to Members of Congress on Capitol Hill,” the Fox Foundation said. “Teed will meet with Senators, Representatives and their staff to talk about the need to provide federal funding for Parkinson’s research programs at the Centers for Disease Control and Prevention, National Institutes of Health, and the Department of Defense.”

“I am honored to attend the 2018 Parkinson’s Policy Forum to represent the Parkinson’s community on Capitol Hill on these important issues,” Teed said. “I reach out to my Senators and Representative year-round at town halls and local meetings, as well as through email and phone calls, but the chance to come together with hundreds of people like me, share our journey and show our nation’s leaders what it means to live with Parkinson’s disease is powerful.”

http://www.columbiatribune.com/news/20180316/teed-to-take-parkinsons-battle-to-dc

Protein analysis for personalised medicine

March 16, 2018 by Pe­ter Rüegg, ETH Zurich

At the axons of neurons, plaques of strucutrally modified proteins (grey) accumulate and are the root cause of neurodegenerative diseases such as Parkinson's or Alzheimer's disease. Credit: selvanegra / istockphoto.com

New knowledge about proteins helps researchers develop innovative solutions for clinical practice, for example to the benefit of patients with Parkinsons's disease.

To this day, there are no therapies that work equally well for all patientsdiagnosed with the same disease. Many conventional therapies are effective in only a limited proportion of cases. And some patients who initially respond to a specific medication later suffer an inexplicable relapse. The one-size-fits-all pill remains an illusory dream.

Take the example of Parkinson's disease: Doctors generally prescribe Levodopa, a drug that relieves some patients of their tremors. In certain cases, however, it accelerates the loss of cognitive functions, thus impairing rather than improving the patient's condition. None of the diagnostic methods available at present enables doctors to predict how or whether a patient will respond to the prescribed treatment – or decide which cases call for an alternative therapeutic approach.

Biomarkers for Parkinson's 

This is the point of departure for protein scientist Paola Picotti's work as part of the ETH Domain's strategic focus area Personalized Health and Related Technologies (PHRT). A professor at the Institute of Molecular Systems Biology, Picotti plans to set up a research project to develop biomarkers for the early detection and subtype classification of Parkinson's disease. The underlying technology comes from the field of proteomics.

While the genome represents the complete set of genetic information that defines a living organism or a virus, the proteome represents the entire set of proteins expressed by a given individual at a given time, under defined conditions: for example, a patient's protein profile as recorded during a health check-up. Proteins, and the amino acids they consist of, are complex molecules that perform many different functions, such as fighting infections (antibodies) or regulating metabolic processes (enzymes). Proteomics is the field of research in which mass spectrometry-based and bioinformatic methods are used to investigate the proteome.

Unlike the genome (the complete set of an organism's DNA sequences), the proteome (the collective term for all proteins in an organism) changes dynamically in response to environmental stimuli, diseases and active drug ingredients. "Specific proteins often provide an indication of whether an organism is healthy or sick," says Picotti. She laid the foundations for her new project a few years ago by developing a protein measurement method that makes it possible to identify not only all "normal" proteins in a random biological sample but also those that are misshapen. This is important when designing systems for the early diagnosis of Parkinson's disease.

It is thought that Parkinson's disease is caused by the formation of amyloid plaques in the brain, which in turn damage the nerve cells. Amyloid plaques are clusters of degenerate proteins that gradually clump together to form insoluble deposits. In her preliminary study of samples obtained from Parkinson's patients, Picotti was able to detect such defective proteins. However, the number of test subjects was too low to produce statistically significant results.

As the next stage in her quest to identify biomarkers for use in the early detection and diagnosis of Parkinson's disease, Picotti now intends to analyse and compare proteins in samples obtained from a large cohort of Dutch patients on two separate occasions: once shortly after the onset of symptoms and the second time ten years later. "We are looking for correlations between structural changes in the proteins and the appearance of symptoms such as loss of cognitive functions," Picotti explains. The study also included a control group of healthy subjects.

The ETH professor hopes this will lead to improved therapy for Parkinson's patients. Most drugs are developed in vitro, i.e. in the laboratory, and may seem to work at this stage but often fail when used to treat real patients. Picotti's approach allows drug candidates to be tested on human tissue and determine how and whether they interact with proteins. The results will allow specialists to distinguish between effective and ineffective drugs, and help tailor solutions to suit individual patients.

Provided by: ETH Zurich

https://medicalxpress.com/news/2018-03-protein-analysis-personalised-medicine.html

AC Immune prepares for a first in human study of a promising positron emission tomography (PET) tracer for Parkinson's disease

March 15, 2018

• First potential PET tracer for Parkinson's disease
• First in human study is scheduled for the second half of 2018
• AC Immune's lead compound is highly selective for alpha-synuclein - a key protein in Parkinson's disease pathology
• New data will be presented at the AAT-AD/PDTM Focus Meeting 2018 in Torino, Italy, today

Lausanne, Switzerland, March 15, 2018 - AC Immune SA (NASDAQ: ACIU), a Swiss-based, clinical stage biopharmaceutical company with a broad pipeline focused on neurodegenerative diseases, today announced a significant step for a first potential PET tracer for Parkinson's disease. It plans to initiate a first in human study, scheduled for the second half of 2018. The new compound is highly selective for alpha-synuclein aggregates, an established target for Parkinson's disease and other diseases with alpha-synuclein pathologies (referred to as synucleinopathies in general). New data will be presented at the AAT-AD/PDTM* Focus Meeting 2018 in Torino, Italy, today, March 15, 2018.

Prof. Andrea Pfeifer, CEO of AC Immune, said: "We are excited about this significant step in our development of potentially the first ever PET tracer for earlier and more accurate diagnosis of Parkinson's disease. This important milestone underlines our vision to become a global leader in precision medicine of neurodegenerative diseases, leveraging our proprietary technology platforms."

This next generation tracer was discovered using the company's proprietary MorphomerTMchemistry technology platform. AC Immune has been successfully collaborating on this program with Biogen since April 2016. The companies will continue to further research, develop and clinically validate this alpha-synuclein PET tracer that will be used as an imaging biomarker for Parkinson's disease with an aim to enable the clinical development of new disease-modifying therapies. This project from AC Immune is being supported by The Michael J. Fox Foundation for Parkinson's Research (MJFF).

Jamie Eberling, PhD, Director of Research Programs at MJFF, commented: "We are very pleased about this next important step in the development of an alpha-synuclein imaging agent. Having a PET tracer to detect and track Parkinson's disease would be transformative for Parkinson's research and patient care."

About the R&D program 
Such alpha-synuclein-PET tracers would help to diagnose Parkinson's disease earlier and more accurately. This technology has multiple advantages including direct detection of alpha-synuclein pathology in patients and the capacity to monitor the efficacy of therapeutics reducing alpha-synuclein aggregates in clinical trials. AC Immune's proprietary MorphomerTM chemistry technology platform is designed to interact with misfolded and aggregated proteins. Promising small molecules have been identified with good selectivity for alpha-synuclein and suitable properties for the development as PET ligands. The ability to precisely diagnose Parkinson's disease and other synucleinopathies and therefore treat patients earlier and more accurately is critical to disease management that uses novel therapeutic approaches. This collaboration with Biogen is non-exclusive, and AC Immune retains intellectual property and commercialization rights.

About alpha-synuclein-PET tracers 
A brain Positron Emission Tomography (PET) scan is an imaging test of the brain involving an imaging device and an imaging agent called a PET tracer. No alpha-synuclein-PET tracer has received regulatory approval for commercial distribution, which represents an important medical need, not only in Parkinson's disease but also in other synucleinopathies such as dementia with Lewy bodies and multiple system atrophy. Once the alpha-synuclein-PET tracer is introduced to the body, it transiently enters the brain and binds to abnormal alpha-synuclein protein structures (Lewy bodies, Lewy neurites etc.). Through the radiotracer on the tracer molecule, the imaging device detects the bound alpha-synuclein imaging agent and creates pictures reflecting the amount and distribution of pathological alpha-synuclein in the brain.

About Parkinson's disease

Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease. Parkinson's disease affects approximately 1% of individuals older than 60 years and causes progressive disability (motor and non-motor symptoms). Current therapies only treat the symptoms of Parkinson's; there is no available treatment that can slow or halt disease progression. The two major neuropathological findings in Parkinson's disease are loss of dopaminergic neurons of the substantia nigra pars compacta and the presence of Lewy bodies and Lewy neurites in which the major constituent is alpha-synuclein. The abnormal accumulations of aggregated alpha-synuclein in Lewy bodies, and mutations in the gene for alpha-synuclein in familial forms of Parkinson's disease, have led to the belief that this protein has a central role in Parkinson's disease. The development of alpha-synuclein pathology appears to correlate with the loss of dopaminergic neurons and subsequent decline in motor performance, making it a highly relevant molecular target for diagnostic approaches.

About The Michael J. Fox Foundation
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 $800 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.

About AC Immune 
AC Immune is a clinical stage Swiss-based biopharmaceutical company focused on neurodegenerative diseases with four product candidates in clinical trials. The Company designs, discovers and develops therapeutic and diagnostic products intended to prevent and modify diseases caused by misfolding proteins. AC Immune's two proprietary technology platforms create antibodies, small molecules and vaccines designed to address a broad spectrum of neurodegenerative indications, such as Alzheimer's disease (AD). The Company's pipeline features nine therapeutic and three diagnostic product candidates. The most advanced of these is crenezumab, a humanized anti-amyloid-ß monoclonal IgG4 antibody that targets monomeric and aggregated forms of amyloid-ß, with highest affinity for neurotoxic oligomers currently in Phase 3 clinical studies for AD. This global program is being conducted by the collaboration partner Genentech (a member of the Roche group). Other collaborations include Biogen, Janssen Pharmaceuticals, Nestlé Institute of Health Sciences, Piramal Imaging and Essex Bio-Technology.

Forward looking statements

This press release contains statements that constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-looking statements are statements other than historical fact and may include statements that address future operating, financial or business performance or AC Immune's strategies or expectations. In some cases, you can identify these statements by forward-looking words such as "may," "might," "will," "should," "expects," "plans," "anticipates," "believes," "estimates," "predicts," "projects," "potential," "outlook" or "continue," and other comparable terminology. Forward-looking statements are based on management's current expectations and beliefs and involve significant risks and uncertainties that could cause actual results, developments and business decisions to differ materially from those contemplated by these statements. These risks and uncertainties include those described under the captions "Item 3. Key Information-Risk Factors" and "Item 5. Operating and Financial Review and Prospects" in AC Immune's Annual Report on Form 20-F and other filings with the Securities and Exchange Commission. Forward-looking statements speak only as of the date they are made, and AC Immune does not undertake any obligation to update them in light of new information, future developments or otherwise, except as may be required under applicable law. All forward-looking statements are qualified in their entirety by this cautionary statement.

For further information, please contact:

In Europe Beatrix Benz AC Immune Corporate Communications Phone: +41 21 345 91 34 E-mail: beatrix.benz@acimmune.com	In the US Lisa Sher AC Immune Investor Relations Phone: +1 970 987 26 54 E-mail: lisa.sher@acimmune.com
Nick Miles/Toomas Kull Cabinet Privé de Conseils s.a. Phone: +41 22 552 46 46 E-mail: miles@cpc-pr.com kull@cpc-pr.com	Ted Agne The Communications Strategy Group Inc. Phone: +1 781 631 3117 E-mail: edagne@comstratgroup.com

/EIN News/ -- Attachment: 

http://www.globenewswire.com/NewsRoom/AttachmentNg/63c2d867-8684-4d19-8d51-676afb01da15

https://health.einnews.com/pr_news/437027810/ac-immune-prepares-for-a-first-in-human-study-of-a-promising-positron-emission-tomography-pet-tracer-for-parkinson-s-disease

Faulty cellular membrane 'mix' linked to Parkinson's disease

March 15, 2018, Johns Hopkins University School of Medicine

Immunohistochemistry for alpha-synuclein showing positive staining (brown) of an intraneural Lewy-body in the Substantia nigra in Parkinson's disease. Credit: Wikipedia

Working with lab-grown human brain cells, Johns Hopkins researchers report they have uncovered a much sought-after connection between one of the most common genetic mutations in Parkinson's disease and the formation of fatty plaques in the brain thought to contribute to the destruction of motor neurons that characterize the disease.

The mutation occurs in a gene that holds the code for GBA1, an enzyme that metabolizes fatty molecules in the cell, which make up most of brain cell membranes. The researchers believe that changes in the mixture of fatty molecules cause protein pieces to stick together in the brain, forming "dead zones" in the brain known as Lewy bodies, which can negatively affect movement, learning and behavior.

A summary of the work was published Jan. 8 in the Proceedings of the National Academy of Sciences.

"We believe this study gives us a better understanding of the effects of GBA1 mutation and its role in the development and progress of Parkinson's disease," says Han Seok Ko, Ph.D., associate professor of neurology at the Johns Hopkins University School of Medicine Institute for Cell Engineering.

According to Ko, Lewy bodies are made of clumps of proteins known as α-synucleins. In healthy cells, single α-synuclein proteins tether together in groups of four, called tetramers, which are more resistant to aggregating in the brain. However, in Parkinson's disease, single α-synucleins stick together in the cell membranes, making it impossible for neurons to properly communicate with one another.

The cellular membrane is like a mosaic where fatty molecules act as the cement that holds proteins in an intricate design. In healthy cells, GBA1 ensures that the "cement" is mixed properly to hold the mosaic together. Ko says he and his team theorized that when GBA1 is mutated, this process goes awry and the cell membrane's composition is changed—determining whether the α-synuclein tetramers can stay in place.

To test this theory, Ko and his team studied the effects of removing GBA1 in lab-grown human neuron cells using CRISPR-Cas9, a gene editing technology. They treated half of the "edited" cells with miglustat, a drug primarily used to block the production of fatty molecules, and observed the protein levels in the cell.

The researchers found that deleting GBA1 increased levels of a particular fatty molecule called glucosylceramide. When glucosylceramide levels rose, they reported, the number of stable α-synuclein tetramers fell. The levels returned to nearly normal with miglustat treatment.

Ko and his team believe that increased levels of glucosylceramide destabilized the cellular membrane mix and caused α-synuclein tetramers to fall out of the mosaic and break into single α-synucleins.

"This is interesting because past studies focused on how GBA1 mutations caused single α-synuclein aggregation, but not its effects on the stable tetramers," says Ko.

The researchers then tested their idea in human neurons collected from patients with GBA1-associated Parkinson's disease and found that—like the lab-grown cells—the human Parkinson's disease cells had about two times more glucosylceramide in their membranes than cells without the Parkinson's mutation. Similarly, the number of single α-synucleins also increased in these cells, and treatment with miglustat effectively restored α-synuclein tetramers to near-normal levels.

In a final test, the researchers wanted to investigate whether replacing GBA1 could restore the function of the membrane mix. After using a virus engineered to add a functional copy of the GBA1 gene into cells, Ko found that ?-synuclein tetramers returned to near-normal levels and the amount of α-synuclein aggregates was reduced.

In the future, the researchers intend to further investigate the impact the GBA1 protein has on the formation of α-synuclein tetramers and overall neuronal health.

First observed in 2004, GBA1-associated Parkinson's disease is the most common of the currently known Parkinson's disease mutations. According to the researchers, 5 to 10 percent of Parkinson's disease patients carry a GBA1 mutation.

More information: Sangjune Kim et al. GBA1 deficiency negatively affects physiological α-synuclein tetramers and related multimers, Proceedings of the National Academy of Sciences (2018). DOI: 10.1073/pnas.1700465115 

Journal reference: Proceedings of the National Academy of Sciences 

Provided by: Johns Hopkins University School of Medicine

https://medicalxpress.com/news/2018-03-faulty-cellular-membrane-linked-parkinson.html

New tissue technique gives stunning 3-D insights into the human brain

 March 15, 2018 by Ryan O'hare, Imperial College London

Imaging method enables researchers to generate stunning 3-D images of human brain tissue. Credit: Imperial College London

Imperial researchers have helped develop a breakthrough imaging technique which reveals the ultra-fine structure of the brain in unprecedented detail.

The next generation method enables researchers to generate 3-D images of fresh and archived brain tissue samples, resulting in stunning images of the human brain at the microscopic level.

Developed through an international collaboration between scientists at Imperial College London and The University of Hong Kong, the researchers believe the technique could help to shed new light on the basis of neurological diseases which affect millions around the world.

Traditionally, imaging brain samples has involved taking small tissue samples cut into ultrathin slices which can be stained to reveal characteristics of interest, such as proteins or other markers associated with disease.

In recent years, however, advances in molecular tagging techniques and the availability of laser microscopes have led to the development of modern tissue clearing techniques.

These techniques make brain tissue transparent and enable researchers to see the anatomical structure in 3-D. However, these techniques were originally developed for rodent brain tissues and there have been very few studies on human tissue.

Technique reveals microscopic brain structures. Top: A small cross section of the cerebellum; Bottom: The close up of a fragment of the same sample, revealing networks of brain cells. Credit: Imperial College London

Many of the problems centred around the unique properties of the human brain, as well as preservation and processing of human tissue at post mortem.

To overcome these problems the team, led by 3 medical students, have developed a new tissue clearing solution, OPTIClear, enabling a wide range of molecular labelling methods for 3-D visualisation of fresh and archival human brain tissue.

Using this new approach, they have been able to stain nerve cells, glial cells and blood vessels, as well as pathological markers such as tangles of tau protein found in the brains of Alzheimer's patients, in exquisite detail and determine how they relate to each other in 3-D space.

"These techniques enable us to reveal the microscopic structure of the human brain in spectacular detail," said Professor Steve Gentleman, Scientific Director of the Parkinson's UK Brain Bank at Imperial College London.

The OPIClear technique enables researchers to 'see through' the tissue (Left: before treatment; Right: After treatment). Credit: Imperial College London

He added: "By using tools such as these in the lab we will be able to visualise how cells interact with each other in 3-D and learn more about the pathways and connections that are damaged in the common neurodegenerative brain conditions which have such an enormous impact on people's lives.

"This work is only made possible by the wonderful altruism of our brain donors and their families."

Researchers can use the technique to visualise markers of disease, such as tangles of tau protein in Alzheimer's (pictured). Credit: Imperial College London

According to the researchers, the method is relatively inexpensive, is time efficient and easy to carry out, and is likely to form the basis for further technique development.

It is hoped that a better understanding of the connections and circuitry of the brain at this level will help uncover the pathologies that underlie the common degenerative diseases of the brain, such as Alzheimer's and Parkinson's disease.

The approach also enables researchers to see the intricate structure of cells themselves. Pictured are dendritic spines—protrusions on the axon 'tail' of brain cells, which allow signals to pass from one cell to another. Credit: Imperial College London

More information: Hei Ming Lai et al. Next generation histology methods for three-dimensional imaging of fresh and archival human brain tissues, Nature Communications (2018). DOI: 10.1038/s41467-018-03359-w 

Journal reference: Nature Communications

Provided by: Imperial College London 

https://medicalxpress.com/news/2018-03-tissue-technique-stunning-d-insights.html

Physically Fit Women Almost 90 Percent Less Likely to Develop Dementia

NEUROSCIENCE NEWS   MARCH 14, 2018
Source: AAN.

According to researchers, women who are physically fit and exercise regularly during midlife are almost 90% less likely to develop dementia later in life than those who were moderately fit.

Among the women who had to stop the exercise test due to problems, 45 percent developed dementia decades later. NeuroscienceNews.com image is in the public domain.

Women with high physical fitness at middle age were nearly 90 percent less likely to develop dementia decades later, compared to women who were moderately fit, according to a study published the March 14, 2018, online issue of Neurology. The study measured the women’s cardiovascular fitness based on an exercise test.

When the highly fit women did develop dementia, they developed the disease an average of 11 years later than women who were moderately fit, or at age 90 instead of age 79.

“These findings are exciting because it’s possible that improving people’s cardiovascular fitness in middle age could delay or even prevent them from developing dementia,” said study author Helena Hörder, PhD, of the University of Gothenburg in Gothenburg, Sweden. “However, this study does not show cause and effect between cardiovascular fitness and dementia, it only shows an association. More research is needed to see if improved fitness could have a positive effect on the risk of dementia and also to look at when during a lifetime a high fitness level is most important.”

For the study, 191 women with an average age of 50 took a bicycle exercise test until they were exhausted to measure their peak cardiovascular capacity. The average peak workload was measured at 103 watts. A total of 40 women met the criteria for a high fitness level, or 120 watts or higher. A total of 92 women were in the medium fitness category; and 59 women were in the low fitness category, defined as a peak workload of 80 watts or less, or having their exercise tests stopped because of high blood pressure, chest pain or other cardiovascular problems.

Over the next 44 years, the women were tested for dementia six times. During that time, 44 of the women developed dementia. Five percent of the highly fit women developed dementia, compared to 25 percent of moderately fit women and 32 percent of the women with low fitness. The highly fit women were 88 percent less likely to develop dementia than the moderately fit women.

Among the women who had to stop the exercise test due to problems, 45 percent developed dementia decades later.

“This indicates that negative cardiovascular processes may be happening in midlife that could increase the risk of dementia much later in life,” Hörder said.

Limitations of the study include the relatively small number of women involved, all of whom were from Sweden, so the results may not be applicable to other populations, Hörder said. Also, the women’s fitness level was measured only once, so any changes in fitness over time were not captured.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Funding: The study was supported by the Swedish Forte Center on Aging and Health, the Swedish Research Council for Health, Working Life and Welfare, Alzheimer’s Association Stephanie B. Overstreet Scholars, Alzheimer’s Association Zenith Award, Sahlgrenska University Hospital, Bank of Sweden Tercentary Foundation, Swedish Brain Power and several Swedish foundations.

Source: Renee Tessman – AAN
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: The study will appear in Neurlogy.

http://neurosciencenews.com/women-fit-dementia-8638/