Stem Cell Clinic

Researchers Say They Have Clue to Early-Onset Parkinson Disease – AJMC.com Managed Markets Network

Patients with early-onset Parkinson disease may have been born with disordered brain cells that mishandled dopamine for decades, according to a study released Monday.

To perform the study, researchers at Cedars-Sinai Medical Center and UCLA generated special stem cells, known as induced pluripotent stem cells (iPSCs), from cells of 3 patients with young-onset Parkinson disease; the patients were aged 30-39 and hadno known familial history of PD or PD mutations.

The process involved taking adult blood cells back to a primitive embryonic state. These iPSCs can then produce any cell type of the human body, all genetically identical to the patient's own cells. The team used the iPSCs to produce dopamine neurons from each patient and then cultured them in a dish and analyzed the neurons' functions.

The researchers detected 2 key abnormalities in the dopamine neurons:

The investigators also used their model to test a number of drugs that might reverse the abnormalities. One drug, PEP005, or ingenol mebutate gel, used for basal cell carcinoma, reduced the elevated levels of alpha-synuclein in both the dopamine neurons in the dish and in laboratory mice.

The drug also countered another abnormality they found in the patients' dopamine neuronselevated levels of an active version of an enzyme called protein kinase C. However, the role of this enzyme version in Parkinson disease is unknown.

In Parkinson, brain neurons that make dopamine, a substance that helps coordinate muscle movement, become impaired or die. The disease is diagnosed in at least 500,000 people in the United States each year, and the incidence is rising. About 10% are aged 21 to 50 years.

Michele Tagliati, MD, director of the Movement Disorders Program, vice chair and professor in the Department of Neurology at Cedars-Sinai, said the team plans to investigate how PEP005 might be delivered to the brain to potentially treat or prevent young-onset Parkinson. The team also plans more research to determine whether the abnormalities the study found in neurons of young-onset Parkinson's patients also exist in other forms of the disease.

Reference

Laperle AH, Sances S, Yucer N, et al.iPSC modeling of young-onset Parkinsons disease reveals a molecular signature of disease and novel therapeutic candidates [published online January 27, 2020].Nat Med.doi: 10.1038/s41591-019-0739-1.

Read this article:
Researchers Say They Have Clue to Early-Onset Parkinson Disease - AJMC.com Managed Markets Network

Revving the Engine – Harvard Medical School

The hearts ability to beat normally over a lifetime is predicated on the synchronized work of proteins embedded in the cells of the heart muscle.

Like a fleet of molecular motors that get turned on and off, these proteins cause the heart cells to contract, then force them to relax, beat after life-sustaining beat.

Now a study led by researchers at Harvard Medical School, Brigham and Womens Hospital and the University of Oxford shows that when too many of the hearts molecular motor units get switched on and too few remain off, the heart muscle begins to contract excessively and fails to relax normally, leading to its gradual overexertion, thickening and failure.

Get more HM news

Results of the work, published Jan. 27 inCirculation,reveal that this balancing act is an evolutionary mechanism conserved across species to regulate heart muscle contraction by controlling the activity of a protein called myosin, the main contractile protein of the heart muscle.

The findingsbased on experiments with human, mouse and squirrel heart cellsalso demonstrate that when this mechanism goes awry it sets off a molecular cascade that leads to cardiac muscle over-exertion and culminates in the development of hypertrophic cardiomyopathy (HCM), the mostcommon genetic diseaseof the heartand aleading causeof sudden cardiac death in young people and athletes.

Our findings offer a unifying explanation for the heart muscle pathology seen in hypertrophic cardiomyopathy that leads to heart muscle dysfunction and, eventually, causes the most common clinical manifestations of the condition, said senior authorChristine Seidman, professor of genetics in the Blavatnik Institute at Harvard Medical School, a cardiologist at Brigham and Womens Hospital and a Howard Hughes Medical InstituteInvestigator.

Importantly, the experiments showed that treatment with an experimental small-molecule drug restored the balance of myosin arrangements and normalized the contraction and relaxation of both human and mouse cardiac cells that carried the two most common gene mutations responsible for nearly half of all HCM cases worldwide.

If confirmed in further experiments, the results can inform the design of therapies that halt disease progression and prevent complications.

Correcting the underlying molecular defect and normalizing the function of heart muscle cells could transform treatment options, which are currently limited to alleviating symptoms and preventing worst-case scenarios such as life-threatening rhythm disturbances and heart failure, said study first authorChristopher Toepfer,who performed the work as a postdoctoral researcher in Seidmans lab and is now a joint fellow in the Radcliffe Department of Medicine at the University of Oxford.

Some of the current therapies used for HCM include medications to relieve symptoms, surgery to shave the enlarged heart muscle or the implantation of cardioverter defibrillators that shock the heart back into rhythm if its electrical activity ceases or goes haywire. None of these therapies address the underlying cause of the disease.

Imbalance in the motor fleet

Myosin initiates contraction by cross-linking with other proteins to propel the cell into motion. In the current study, the researchers traced the epicenter of mischief down to an imbalance in the ratio of myosin molecule arrangements inside heart cells. Cells containing HCM mutations had too many molecules ready to spring into action and too few myosin molecules idling standby, resulting in stronger contractions and poor relaxation of the cells.

An earlier study by the same team found that under normal conditions, the ratio between on and off myosin molecules in mouse heart cells is around 2-to-3. However, the new study shows that this ratio is off balance in heart cells that harbor HCM mutations, with disproportionately more molecules in active versus inactive states.

In an initial set of experiments, the investigators analyzed heart cells obtained from a breed of hibernating squirrel as a model to reflect extremes in physiologic demands during normal activity and hibernation. Cells obtained from squirrels in hibernationwhen their heart rate slows down to about six beats per minutecontained 10 percent more off myosin molecules than the heart cells of active squirrels, whose heart rate averages 340 beats per minute.

We believe this is one example of natures elegant way of conserving cardiac muscle energy in mammals during dormancy and periods of deficient resources, Toepfer said.

Next, researchers looked at cardiac muscle cells from mice harboring the two most common gene defects seen in HCM. As expected, these cells had altered ratios of on and off myosin reserves.The researchers also analyzed myosin ratios in two types of human heart cells: Stem cell-derived human heart cells engineered in the lab to carry HCM mutations and cells obtained from the excised cardiac muscle tissue of patients with HCM. Both had out-of-balance ratios in their active and inactive myosin molecules.

Further experiments showed that this imbalance perturbed the cells normal contraction and relaxation cycle. Cells harboring HCM mutations contained too many on myosin molecules and contracted more forcefully but relaxed poorly. In the process, the study showed, these cells gobbled up excessive amounts of ATP, the cellular fuel that sustains the work of each cell in our body. And because oxygen is necessary for ATP production, the mutated cells also devoured more oxygen than normal cells, the study showed. To sustain their energy demands, these cells turned to breaking down sugar molecules and fatty acids, which is a sign of altered metabolism, the researchers said.

Taken together, our findings map out the molecular mechanisms that give rise to the cardinal features of the disease, Seidman said. They can help explain how chronically overexerted heart cells with high energy consumption in a state of metabolic stress can, over time,lead to a thickened heart muscle that contracts and relaxes abnormally and eventually becomes prone to arrhythmias, dysfunction and failure.

See more here:
Revving the Engine - Harvard Medical School

Divorce as Seen Through the Eyes of a Child – SWAAY

With so many groundbreaking medical advances being revealed to the world every single day, you would imagine there would be some advancement on the plethora of many female-prevalent diseases (think female cancers, Alzheimer's, depression, heart conditions etc.) that women are fighting every single day.

For Anna Villarreal and her team, there frankly wasn't enough being done. In turn, she developed a method that diagnoses these diseases earlier than traditional methods, using a pretty untraditional method in itself: through your menstrual blood.

Getting from point A to point B wasn't so easy though. Villarreal was battling a disease herself and through that experience. I wondered if there was a way to test menstrual blood for female specific diseases," she says. "Perhaps my situation could have been prevented or at least better managed. This led me to begin researching menstrual blood as a diagnostic source. For reasons the scientific and medical community do not fully understand, certain diseases impact women differently than men. The research shows that clinical trials have a disproportionate focus on male research subjects despite clear evidence that many diseases impact more women than men."

There's also no denying that gap in women's healthcare in clinical research involving female subjects - which is exactly what inspired Villarreal to launch her company, LifeStory Health. She says that, with my personal experience everything was brought full circle."

There is a challenge and a need in the medical community for more sex-specific research. I believe the omission of females as research subjects is putting women's health at risk and we need to fuel a conversation that will improve women's healthcare.,"

-Anna Villarreal

Her brand new biotech company is committed to changing the women's healthcare market through technology, innovation and vocalization and through extensive research and testing. She is working to develop the first ever, non-invasive, menstrual blood diagnostic and has partnered with a top Boston-area University on research and has won awards from The International Society for Pharmaceutical Engineering and Northeastern University's RISE.

How does it work exactly? Proteins are discovered in menstrual blood that can quickly and easily detect, manage and track diseases in women, resulting in diseases that can be earlier detected, treated and even prevented in the first place. The menstrual blood is easy to collect and since it's a relatively unexplored diagnostic it's honestly a really revolutionary concept, too.

So far, the reactions of this innovative research has been nothing but excitement. The reactions have been incredibly positive." she shares with SWAAY. Currently, menstrual blood is discarded as bio waste, but it could carry the potential for new breakthroughs in diagnosis. When I educate women on the lack of female subjects used in research and clinical trials, they are surprised and very excited at the prospect that LifeStory Health may provide a solution and the key to early detection."

To give a doctor's input, and a little bit more of an explanation as to why this really works, Dr. Pat Salber, MD, and Founder of The Doctor Weighs In comments: researchers have been studying stem cells derived from menstrual blood for more than a decade. Stem cells are cells that have the capability of differentiating into different types of tissues. There are two major types of stem cells, embryonic and adult. Adult stem cells have a more limited differentiation potential, but avoid the ethical issues that have surrounded research with embryonic stem cells. Stem cells from menstrual blood are adult stem cells."

These stem cells are so important when it comes to new findings. Stem cells serve as the backbone of research in the field of regenerative medicine the focus which is to grow tissues, such as skin, to repair burn and other types of serious skin wounds.

A certain type of stem cell, known as mesenchymal stem cells (MenSCs) derived from menstrual blood has been found to both grow well in the lab and have the capability to differentiate in various cell types, including skin. In addition to being used to grow tissues, their properties can be studied that will elucidate many different aspects of cell function," Dr. Salber explains.

To show the outpour of support for her efforts and this major girl power research, Villarreal remarks, women are volunteering their samples happily report the arrival of their periods by giving samples to our lab announcing de-identified sample number XXX arrived today!" It's a far cry from the stereotype of when it's that time of the month."

How are these collections being done? Although it might sound odd to collect menstrual blood, plastic cups have been developed to use in the collection process. This is similar to menstrual products, called menstrual cups, that have been on the market for many years," Dr. Salber says.

Equally shocking and innovative, this might be something that becomes more common practice in the future. And according to Dr. Salber, women may be able to not only use the menstrual blood for early detection, but be able to store the stem cells from it to help treat future diseases. Companies are working to commercialize the use of menstrual blood stem cells. One company, for example, is offering a patented service to store menstrual blood stem cells for use in tissue generation if the need arises."

Original post:
Divorce as Seen Through the Eyes of a Child - SWAAY

Diabetes-related proteins examined for the first time at high resolution – Drug Target Review

A key receptor has been examined for the first time at high resolution which could lead to better treatments for conditions such as type 2 diabetes.

Scientists have examined a key receptor for the first time at high resolution which, they say, broadens understanding of how it might function and opens the door to future improvements in treating conditions such as type 2 diabetes.

The scientists were led by experts at the University of Birmingham, UK and the Max Planck Institute for Medical Research, Germany.

Glucagon-like peptide-1 receptors (GLP1R) are found on insulin-producing beta cells of the pancreas and neurons in the brain. The receptor encourages the pancreas to release more insulin, stops the liver from producing too much glucose and reduces appetite. This combination of effects can help to control blood sugar levels.

Therefore, GLP1R has become a significant target for the treatment of type 2 diabetesand a range of drugs are now available that are based on it. But much remains unknown about GLP1R function because its small size makes it difficult to visualise.

Our research allows us to visualise this key receptor in much more detail than before, David Hodson, Professor of Cellular Metabolism at the University of Birmingham. Think about watching a movie in standard definition versus 4k, thats how big the difference is. We believe this breakthrough will give us a much greater understanding of GLP1R distribution and function. Whilst this will not immediately change treatment for patients, it might influence how we design drugs in the future.

GLP1R visualized in insulin-secreting beta cells at super-resolution (credit: University of Birmingham).

The researchers used a number of techniques to conduct a detailed examination of the receptor in living cells including synthesis of marker compounds, immunostaining, super-resolution microscopy, as well as in vivo examination of mice.

Our experiments, made possible by combining expertise in chemistry and cell biology, will improve our understanding of GLP1R in the pancreas and the brain. Our new tools have been used in stem cells and in the living animal to visualise this important receptor and we provide the first super-resolution characterisation of a class B GPCR. Importantly, our results suggest a degree of complexity not readily appreciated with previous approaches, added Johannes Broichhagen, Departmental Group Leader of the Max-Planck Institute for Medical Research.

The findings were published in Nature Communications.

Read the original here:
Diabetes-related proteins examined for the first time at high resolution - Drug Target Review

StemoniX’s microBrain to be Featured in Podium Presentation at SLAS 2020 International Conference & Exhibition – BioSpace

MAPLE GROVE, Minn., Jan. 27, 2020 /PRNewswire/ --StemoniX, a biotech company revolutionizing how new medicines are discovered, announced today that its Director of Applications, Oivin Guichert, Ph.D., will deliver a podium presentation highlighting the company's microBrain technology at the SLAS (Society for Laboratory Automation and Screening) 2020 International Conference & Exhibition at the San Diego Convention Center, Jan. 27-29, 2020. The presentation will be featured as part of the Assay Development and Screening Session during the annual meeting.

During the podium presentation, entitled "New innovation to solve unmet needs: Implementing human induced pluripotent stem cell-derived neural spheroids as a robust screening platform for phenotypic-based central nervous system drug discovery," Dr. Guichert will detail how performing a high-throughput functional screening assay on StemoniX's human induced pluripotent stem cell (iPSC)-derived 3D neural spheroid platform demonstrated the ability to identify a wide range of hits spanning multiple target areas. He will highlight how this model could provide relevant human platforms for disease-specific drug discovery to help overcome traditional hurdles of CNS-targeted drug discovery and development efforts.

Ping Yeh, co-founder and CEO of StemoniX, said: "The SLAS 2020 International Conference & Exhibitionis an ideal event to showcase the value potential of our microOrgan platform and AnalytiX data management and analytical software. As presented by Dr. Guichert and in the six posters, microBrain, microHeart, microPancreas and AnalytiX offer the potential to reshape how drugs are discovered and developed by providing the opportunity to go from model to molecule to validated drug in a fraction of the time and cost required with traditional methods. This includes the near-term potential to identify and advance novel therapeutic targets for Rett syndrome by leveraging our groundbreaking in vitro microBrain model in partnership with AI drug discovery pioneer, Atomwise."

Podium Presentation Details

Title:

New innovation to solve unmet needs: Implementing human induced pluripotent stem cell-derived neural spheroids as a robust screening platform for phenotypic-based central nervous system drug discovery

Session:

Assay Development and Screening

Event

SLAS 2020 International Conference & Exhibition

Date:

Tuesday, January 28, 2020

Time:

4:00 4:30 p.m. PST

Location:

San Diego Convention Center

Room/Location:

6C

Poster Presentations:

About StemoniXStemoniX is accelerating the discovery of new medicines to treat challenging diseases via the world's first ready-to-use assay plates containing living human microOrgans, including electrophysiologically active neural (microBrain) and cardiac (microHeart) cells. Predictive, accurate, and consistent, StemoniX's products combined with its proprietary data management and analytical tools (AnalytiX) are revolutionizing traditional drug discovery and development by radically improving the speed, accuracy and costs required to identify new drugs and conduct initial human cell toxicity and efficacy testing. Through its Discovery as a Service offering, the company partners with organizations to screen compounds as well as to create customized microOrgan models and assays tailored to specific discovery and toxicity needs. Visit http://www.stemonix.com to learn how StemoniX is helping global institutions humanize drug discovery and development to bring the most promising medicines to patients.

Tiberend Strategic Advisors, Inc.

Investor Contact:Maureen McEnroe, CFA+1.212.375.2664mmcenroe@tiberend.com

Media Contact:Ingrid Mezo+1.646.604.5150imezo@tiberend.com

View original content to download multimedia:http://www.prnewswire.com/news-releases/stemonixs-microbrain-to-be-featured-in-podium-presentation-at-slas-2020-international-conference--exhibition-300993663.html

SOURCE StemoniX

Go here to see the original:
StemoniX's microBrain to be Featured in Podium Presentation at SLAS 2020 International Conference & Exhibition - BioSpace

5 of the biggest medical advances of the past decade – Health24

Every year, medical technology further evolves, and new discoveries are made. This brings hope to those suffering from grave medical conditions. Health24 covers these advances on an ongoing basis, and the following are a few of the biggest breakthroughs of the decade in a nutshell:

The past decade has seen a number of medical headlines involving 3D-organ-printing, up to the point where, recently, researchers managed to create living skin, complete with blood vessels, as well as hearts. While many of these advancements need more research before they can be used in a clinical setting, 3D-printing is set to become more prevalent over the next the next decade, which will make transplanting easier for those in need.

Health24 published several stories about gene therapy over the last ten years. And while there were restrictions placed on gene therapy research in the early 2000s, there's been a strong resurgence, as illustrated by this study focusing on gene therapy in the fight against leukaemia.

Despite a number of setbacks, there were some successes that could translate to treatments in the future. One of the most recent development involves the first clinical trial of its type. Researchers used CRISPR to edit the DNA of peoples immune systems to help treat certain cancers.

While only a small number of patients were involved in the Stage 1 clinical trial, experts believe that this was an important step, in that it proved that the technique is safe to use.

Read more about gene therapy here.

The focus on gut health and our microbiome (the collection of bacteria in the gut) has never been stronger. In the past, researchers didnt pay much attention to the role of the bacteria in our gut, and it's been mainly during the past 15 years that researchers have been studying this concept.

According to the BMJ, the gut microbiota is crucial for essential processes in the body, such as the fermentation of non-digestible dietary fibres. It does more than that, though, and plays a role in many key areas of human health, from our immunity and appetite to the way we digest our food.

This helped researchers to explore the role of gut bacteria in areas like depression. An article in the BMJ reports on changes in the gut microbiota in the case of not only obesity, diabetes, and liver disease, but also cancer and even neurodegenerative diseases.

In fact, a study covered by Health24 links gut microbes to chronic fatigue syndrome, a condition that has been baffling experts for decades.

HIV and Aids remain important public healthcare topics in South Africa. During the past decade, antiretroviral treatment has improved and become more readily available. In fact, the virus is currently controlled so well that the viral load in many patients' blood has become virtually undetectable.

According to Pharmaceutical Technologies, various studies over the past decade found that treatment with antiretroviral therapy has also reduced the risk of spreading the infection to HIV-negative partners in both homosexual and heterosexual couples.

A few months ago, Health24 published a story about a man simply known as the London patient, who became entirely free from HIV following stem cell treatment for Hodgkin's Lymphoma. He was the second patient to demonstrate this phenomenon.

In 2017, a man known as the Berlin patient had two copies of the CCR5-delta32 genetic mutation. The patient stopped his ART 16 months following a bone marrow transplant, and his blood viral load was still undetectable 18 months later.

Canceris one of the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases reported annually, according to the World Health Organization. Experts say immunotherapy is a promising new development, and ongoing research has been conducted over the past decade.

In one of the latest studies, Dr Christopher E. Rudd, a researcher at the Centre de Recherche de l'Hpital Maisonneuve-Rosemont (CR-HMR) and Universit de Montral, discovered a new cell therapy approach that boosts the immune response of T lymphocytes to malignant tumours. The results of the study were recently published in the respected journal Nature.

Image credit: iStock

Compiled by Marelize Wilke

Read the original here:
5 of the biggest medical advances of the past decade - Health24

Scientists Have Grown Snake Venom Glands in The Lab. Here’s Why That’s Awesome – ScienceAlert

For the first time, scientists have produced snake venom toxins in the lab, opening up a much-needed path for developing drugs and venom antidotes that doesn't involve having to breed and milk real-life snakes.

The toxins have been produced through mini glands called organoids, following a process adapted from growing simplified human organs something that is already helping in a wide range of scientific and medical research projects.

In the case of the snakes, researchers were able to blow organoids matching the Cape coral snake (Aspidelaps lubricus cowlesi) and seven other snake species, and they say this new approach is a welcome upgrade on current methods of farming snakes to extract their venom.

"More than 100,000 people die from snake bites every year, mostly in developing countries," says molecular biologist Hans Clevers, from Utrecht University in the Netherlands. "Yet the methods for manufacturing antivenom haven't changed since the 19th century."

By tweaking the recently developed process for growing human organoids including reducing the temperature to match reptiles rather than mammals the researchers were able to find a recipe that supports the indefinite growth of tiny snake venom glands.

Tissue was removed from snake embryos and put into a gel mixed with growth factors, but access to stem cells which is how human and mouse organoids are usually developed wasn't required.

The cells quickly began dividing and forming structures, giving the team hundreds of growing samples in the space of a couple of months, and producing small white blobs from which venom toxins could be harvested.

Al least four distinct types of cell were identified by the researchers within the artificially grown venom glands, and they were also able to confirm that the venom peptides produced were biologically active, closely resembling those in live snake venom.

Snake venom gland organoids. (Ravian van Ineveld/Princess Mxima Center)

"We know from other secretory systems such as the pancreas and intestine that specialised cell types make subsets of hormones," says developmental biologist Joep Beumerfrom Utrecht University.

"Now we saw for the first time that this is also the case for the toxins produced by snake venom gland cells."

The use of snake venom toxins to develop medicines and treatments has been going on since the time of ancient Greece. In the modern age, drugs fighting everything from cancer to haemorrhages have been developed with the help of toxins we find in snake venom.

Having faster and more controlled access to these toxins could mean these treatments can be developed more easily and on a shorter time scale, say the researchers.

Besides drug development, these organoid venom glands should make it easier and faster to develop antivenoms and with so many people suffering deaths, injuries or disabilities because of snake bites, that will make a considerable difference.

"It's a breakthrough," snake venom toxicologist Jos Mara Gutirrez from the University of Costa Rica, told Science.

"This work opens the possibilities for studying the cellular biology of venom-secreting cells at a very fine level, which has not been possible in the past."

The research has been published in Cell.

The rest is here:
Scientists Have Grown Snake Venom Glands in The Lab. Here's Why That's Awesome - ScienceAlert