Category Archives: Adult Stem Cells

Global Mesenchymal Stem Cells Market to Witness Exponential Rise in Revenue Share During the Forecast Period – Lake Shore Gazette

Mesenchymal stem cells are the adult stem cells. Mesenchymal stem cells are of various types such as monocytes, adipocytes, osteocytes and chondrocytes. Mesenchymal stem cells main function is to replace or repair damage tissue. In addition, mesenchymal stem cells have high potential for tissue repair. Mesenchymal stem cells are isolated from other tissues such as fallopian tube, cord blood, fetal liver, peripheral blood and fetal lung. Mesenchymal stem cells are renewable source to substitute tissue and cells to treat disabilities and diseases.

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North America dominates the global market for mesenchymal stem cell due to large number of aging population and increasing incidence of cancers. Asia is expected to show high growth rates in the next five years in the global mesenchymal stem cell market. China and India are expected to be the fastest growing mesenchymal stem cell markets in Asia-Pacific region. Some of the key driving forces for mesenchymal stem cell market in emerging countries are large pool of patients and rising government funding and support.

In recent times there is increased use of mesenchymal stem cell due to increasing aging population. Rising incidence of chronic diseases, regulatory and government support and increasing investment in stem cell biology are some of the key factors driving the growth for the global mesenchymal stem cell market. In addition, increasing use of mesenchymal stem cell as a substitute to knee replacement surgeries and other operative procedures is also fuelling the growth of the global mesenchymal stem cell market. However, lack of therapeutic advancement related to vitro properties of stem cell is the major factor restraining the growth for the global mesenchymal stem cell market.

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Numerous ethical, political and religious controversies on mesenchymal stem cell could lead a challenge for the global mesenchymal stem cell market. Some of the trends for the global mesenchymal stem cell market are increasing collaborations and partnerships and rising innovation of mesenchymal stem cell products. Some of the major companies operating in the global mesenchymal stem cell market are EMD Millipore Corporation, Cell Applications, Inc., Cyagen Biosciences, Inc., Genlantis, Inc., Advanced Cell Technology Incorporated, Stemcell Technologies Inc., Celprogen, Inc., Stemedica Cell Technologies, Aastrom Biosciences and ScienCell Research Laboratories.

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Global Mesenchymal Stem Cells Market to Witness Exponential Rise in Revenue Share During the Forecast Period – Lake Shore Gazette

Keeping kids and adults alike healthy with Colostrum – North Coast Courier

Did you know that your childs immune system isnt fully developed until the age of 7 or 8 years, and that they are exposed to thousands of germs each and every day?

Kids will be kids, and who we cannot keep them wrapped in bubble wrap but there are ways to strengthen their immune response.

Key to doing this is to maintain and strengthen your childs gut health.

Ballito based New Image International consultant, Prema Naidoo recommends the Alpha Lipid Dinotabs a Colostrum-based product in the form of a tablet which children can take daily from the age of 12 months and upwards.

Containing Bovine Colostrum, these strawberry flavoured tablets provide important immune factors antibodies which may help your child to cope with the constant challenges they may face with their immune health.

Bovine Colostrum is a milky fluid which comes from the udders of cows during the first few days after giving birth (before true milk appears) this is filled with proteins, carbohydrates, fats, vitamins, minerals and specific kinds of proteins called antibodies, which help fight bacteria and viruses.

Taken daily, Colostrum supports digestion by providing nutrients to your child which nourishes a healthy digestive tract.

Dinotabs also improves bone and dental health.

And while youre busy running after your child, you may need something to aid with replenishing, rejuvenating and revitalising your own bodys natural cellular repair process. This can be done by taking Alpha Lipid Colostem, which supports stem cell nutrition.

Colostrum has stem cell releasing properties. Stem cells have the ability to develop into many different cell types, which can range from muscle cells to brain cells.

Acting as a universal repair system while also maintaining the regeneration of cells throughout the body, adult stem cells divide to replenish dying cells.

Alpha Lipid Colostem supports this natural process, adding antioxidants and nutrients to boost your immunity and leave your body feeling restored, healthy and protected.

For more information, contact Prema Naidoo at 079 694 7893.

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Keeping kids and adults alike healthy with Colostrum – North Coast Courier

Newly discovered molecule could play key role in treating osteoarthritis – Irish Examiner

A newly discovered molecule has the potential to play a role in treating osteoarthritis, after researchers found it provided long-lasting regeneration of bone and cartilage defects in animals.

Osteoarthritis is a condition that causes joints to become painful and stiff and is the most common type of arthritis in the UK, affecting nearly 9 million people.

Cartilage, which overlies bones to enable frictionless movement in joints, often fails to repair after injury which leads to further cartilage loss and osteoarthritis.

There is no cure for arthritis, with treatments only helping to slow it down.

A team of researchers, led by Queen Mary University of London in England, studied the effects of a molecule called agrin on animals and discovered that it repairs cartilage by recruiting and activating adult stem cells present in the joint.

Scientists explained that these mechanisms were the same as those used by a body first developing a skeleton in the embryo.

Their study, published in Science Translational Medicine journal, suggests that supporting such mechanisms is an effective way to help heal injuries that are too big to heal in normal conditions.

Researchers injected mice with a gel containing agrin into joint surface defects and after eight weeks found it caused long-lasting regeneration of bone and cartilage more than a control group that received the gel without agrin.

Testing the agrin-containing gel on sheep also found cartilage and bone repair was better after six months, when compared to a control group.

Researchers said the sheep spent more time playing and less time resting during the study, suggesting the repair improvement was associated with improved function.

Dr Suzanne Eldridge, from Queen Mary University of London, said osteoarthritis costs the UK 13 billion a year when factoring in indirect costs such as carers and being out of employment.

She explained the condition leaves people severely disabled and there is no cure.

Many are unable to do basic things, including bathing, getting dressed, cooking or shopping, she said.

This week’s new issue of Science Translational Medicine has arrive! https://t.co/UcX7IPgRNN pic.twitter.com/raEEs3AES8

Dr Eldridge added: If we could intervene at an early stage once an injury has occurred, and repair the damage, the likelihood of patients going on to develop osteoarthritis is much slimmer.

Our ultimate aim is to transform osteoarthritis from a disease that requires surgery, to one that just requires an injection.

Professor Francesco DellAccio, also from Queen Mary University of London, said: Weve shown that its possible to repair joint defects, for the moment at least in animals, not just in the bone but also in the cartilage.

One single administration of this molecule is sufficient to trigger a cascade of events in the joints, which, once started, are then self-maintained.

Not only does it achieve structural repair, but weve shown that it gives symptomatic relief in animals extremely rapidly.

Researchers are now working towards applying their findings safely in humans but predict clinical trials are several years away.

The study was funded by the Medical Research Council, charity Versus Arthritis, Reumafond, a Dutch arthritis foundation, and private medical research charity The Rosetrees Trust.

It also involved researchers from Scotland’s University of Aberdeen and England’s University of Cambridge.

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Newly discovered molecule could play key role in treating osteoarthritis – Irish Examiner

Stem Cell Therapy Market (Covid 19 Impact) Research Outlook, Recent Trends and Growth Forecast 2020-2025 – TC BizNews

The Stem Cell Therapy report provides independent information about the Stem Cell Therapy industry supported by extensive research on factors such as industry segments size & trends, inhibitors, dynamics, drivers, opportunities & challenges, environment & policy, cost overview, porters five force analysis, and key companies profiles including business overview and recent development.

Stem Cell Therapy MarketLatest Research Report 2020:

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In this report, our team offers a thorough investigation of Stem Cell Therapy Market, SWOT examination of the most prominent players right now. Alongside an industrial chain, market measurements regarding revenue, sales, value, capacity, regional market examination, section insightful information, and market forecast are offered in the full investigation, and so forth.

Scope of Stem Cell Therapy Market: Products in the Stem Cell Therapy classification furnish clients with assets to get ready for tests, tests, and evaluations.

Major Company Profiles Covered in This Report

Gilead,Novartis,Organogenesis,Vericel

Stem Cell Therapy Market Report Covers the Following Segments:

Product Type: Adult Stem Cells, Human Embryonic Stem Cells (hESC), Induced Pluripotent Stem Cells, Very Small Embryonic Like Stem Cells

Application: Regenerative Medicine, Drug Discovery and Development

North America

Europe

Asia-Pacific

South America

Center East and Africa

United States, Canada and Mexico

Germany, France, UK, Russia and Italy

China, Japan, Korea, India and Southeast Asia

Brazil, Argentina, Colombia

Saudi Arabia, UAE, Egypt, Nigeria and South Africa

Market Overview:The report begins with this section where product overview and highlights of product and application segments of the global Stem Cell Therapy Market are provided. Highlights of the segmentation study include price, revenue, sales, sales growth rate, and market share by product.

Competition by Company:Here, the competition in the Worldwide Stem Cell Therapy Market is analyzed, By price, revenue, sales, and market share by company, market rate, competitive situations Landscape, and latest trends, merger, expansion, acquisition, and market shares of top companies.

Company Profiles and Sales Data:As the name suggests, this section gives the sales data of key players of the global Stem Cell Therapy Market as well as some useful information on their business. It talks about the gross margin, price, revenue, products, and their specifications, type, applications, competitors, manufacturing base, and the main business of key players operating in the global Stem Cell Therapy Market.

Market Status and Outlook by Region:In this section, the report discusses about gross margin, sales, revenue, production, market share, CAGR, and market size by region. Here, the global Stem Cell Therapy Market is deeply analyzed on the basis of regions and countries such as North America, Europe, China, India, Japan, and the MEA.

Application or End User:This section of the research study shows how different end-user/application segments contribute to the global Stem Cell Therapy Market.

Market Forecast:Here, the report offers a complete forecast of the global Stem Cell Therapy Market by product, application, and region. It also offers global sales and revenue forecast for all years of the forecast period.

Research Findings and Conclusion:This is one of the last sections of the report where the findings of the analysts and the conclusion of the research study are provided.

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Stem Cell Therapy Market (Covid 19 Impact) Research Outlook, Recent Trends and Growth Forecast 2020-2025 – TC BizNews

Shielded Stem Cells Improve The Cells’ Ability To Heal Heart Injuries – Interesting Engineering

A heart attack survivor’s heart might just get fully recovered thanks to this development.

When one experiences a heart attack, it is not certain whether they will fully recover or not. Even if the survivor goes back to his regular life, physical restrictions might be necessary due to heart scarring that occurs after the attack.

Bioengineers and surgeons fromRice University and Baylor College of Medicine (BCM) have developed a biomaterial containing stem cells to help repair the heart tissue damage that forms after a heart attack.

The research was published in the journalBiomaterials Science.

In fact, stem cells have been used to try and repair the heart tissue that was damaged before. A type of adult stem cell produced in blood marrow called mesenchymal stem cells (MSCs) was considered helpful in tissue repair. However, the immune system combatted them.

They thought the cells alone were not to correspond to the immune system.

RELATED: NEW BIOMARKER FINGERPRINT WITH AI TECHNOLOGY CAN NOW PREDICT FUTURE HEART ATTACKS

“The immune system perceives them as foreign. And so very rapidly, the immune system starts chewing at them and clearing them out.” saidOmid Veiseh, one of the research leaders.

So basically what they did was to coat the stem cells with a biocompatible hydrogel capsule made of brown algae. Next, they were put in rodents, next to scarred tissue of their hearts. At the end of four weeks, the rodents with shielded stem cells healed 2.5 times better and faster compared to those with non-shielded stem cells.

Samira Aghlara-Fotovat, a graduate student and co-author of the study working in Veiseh’s lab, generated 0,05-inch (1.5-millimeter) capsules that each contained around 30,000 MSCs.

“The immune system doesn’t recognize our hydrogels as foreign, and doesn’t initiate a reaction against the hydrogel,” Veiseh added.

In fact, regulations of scarred tissues are operated by a protein called “type 5 collagen.” So if one lacks the mentioned collagen or has it in small levels, it is likely that damaged tissue will have a hard time being repaired.

Have the capsules been tried on humans yet? Unfortunately, they haven’t. But the thing is that encapsulation technologies designed to be compatible with immune system are already being developed for chronic diseases atSigilon Therapeutics, a Cambridge, Massachusetts-based biotech company. So it is a promising development that most probably will be used on humans soon.

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Shielded Stem Cells Improve The Cells’ Ability To Heal Heart Injuries – Interesting Engineering

Steadman Philippon Research Institute (SPRI) Receives Multi-Million-Dollar Matching Grant from the National Institutes of Health – GlobeNewswire

August 20, 2020 15:02 ET | Source: Steadman Philippon Research Institute

VAIL, Colorado, Aug. 20, 2020 (GLOBE NEWSWIRE) — Steadman Philippon Research Institute (SPRI) has been granted the prestigious Regenerative Medicine Innovation Project Investigator-Initiated Clinical Trials award from the National Institutes of Health (NIH). SPRI Chief Scientific Officer Johnny Huard, Ph.D. will serve as the principal investigator. Marc J. Philippon, M.D., who serves as managing partner of The Steadman Clinic and co-chair of SPRI and Scott Tashman, Ph.D., director of biomedical engineering at SPRI, will serve as co-principal investigators. The clinical trials are expected to begin enrolling in the Fall of 2020.

The award, administered by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, ranks as one of the most significant in SPRIs history, both in size and recognition. Given the potential of regenerative medicine to enhance human health and treat disease, the United States Congress included a provision in the 21st Century Cures Act a law passed in December 2016 to accelerate medical discovery and innovation to support the NIH-established Regenerative Medicine Innovation Project (RMIP). The RMIP aims to accelerate the field by supporting clinical research on adult stem cells while promoting the highest standards for protecting patient safety during the conduct of research.

This is a really great honor for SPRI, said Dr. Huard, who first came to Vail in 2015 and has served as the director of the Center for Regenerative Sports Medicine in addition to his role as the institutes chief scientific officer. Past recipients of these RMIP awards have been Albert Einstein College of Medicine, Boston Childrens Hospital, Columbia University Health Sciences, Childrens Hospital of Philadelphia, Harvard University, University of Colorado Denver and Yale University.So, we are in very good company.

The grant anticipates over $2.8 million from the NIH and requires a 1:1 match from SPRI over the next five years, pending availability of federal funds. The clinical trials and resulting publications and reports will take place over the next five years. A generous SPRI benefactor committed to fund the first year of the match, and Dr. Huard is hopeful that with the NIH matching the funds, more philanthropists will be inspired to become involved in this groundbreaking project.

Our donors have been so generous in supporting all that we do here at SPRI, said Dr. Huard, and I am very grateful and confident that we will raise the funds necessary to complete these trials over the next five years.

The trial is entitled,The Use of Senolytic and Anti-Fibrotic Agents to Improve the Beneficial Effect of Bone Marrow Stem Cells for Osteoarthritis. Huard explains in laypersons terms:

The idea behind the trial is to delay osteoarthritis in the knee, said Huard. Our goal is to delay the need for that first knee replacement in a patient for as long as we can. Over time SPRI intends to expand this area of research to other joints including hip and shoulder.

This clinical trial is designed to determine whether senolytic and/or antifibrotic agents will improve the beneficial effect of Bone Marrow Stem Cells for the treatment of symptomatic knee osteoarthritis. The trial will include four groups, totaling 100 patients, to investigate the teams hypothesis that the use of these agents will improve patient outcomes.

One of the great things that I love about this particular clinical trial is that we are actively involving our orthopaedic surgeons and our biomotion lab staff as well, said Dr. Huard. This will truly be a team effort over the next five years.

Those world-class surgeons are led by Dr. Philippon, considered one of the worlds foremost orthopaedic surgeons. The biomotion lab is under the direction of Dr. Tashman. The contributions of these two leaders and the talented roster of surgeons, clinicians and technicians in their departments will be critical to the success of the upcoming clinical trials. SPRIs Center for Outcomes-Based Orthopaedic Research and its director Grant Dornan are also participating in this project by contributing the statistical outcomes.

Dr. Philippon is not only a world-class surgeon but he is also an innovator, added Dr. Huard. He always wants to improve and is still willing to try new things to enhance patient outcomes. Dr. Tashman is the same way. Like everyone here at SPRI and The Steadman Clinic, they are embracing the cutting-edge technology available to them and finding new and better ways to treat patients and, most importantly, reduce patients recovery time and get them back to their active lives as quickly and safely as possible.

Huard notes that the rare combination of a globally recognized research institute like SPRI and a world-class orthopaedic surgery clinic like The Steadman Clinic in the same building is one of the key factors in the awarding of this RMIP grant.

Weve got something here in Vail that many other research institutes dont have, said Huard. We have one of the worlds finest orthopaedic clinics right next door, working hand-in-hand with us every day.

Dr. Huard and Dr. Tashman along with Suzanne Liv Page, J.D., our director of grants and contracts have worked diligently to prepare and gain acceptance of this grant proposal from the NIH, said Dr. Philippon. Our surgeons here at The Steadman Clinic eagerly await the opportunity to participate in the trial. Johnny, Scott and their staff have put SPRI into position to undertake major trials and studies like this one and we are all very honored that the NIH has given SPRI this incredible opportunity.

For further information or other inquiries about The Steadman Clinic or Steadman Philippon Research Institute, contact Lynda Sampson, Vice President of External Affairs (lsampson@sprivail.org).

Link to current SPRI clinical trials – https://www.sprivail.org/about-us/clinical-trials

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Steadman Philippon Research Institute (SPRI) Receives Multi-Million-Dollar Matching Grant from the National Institutes of Health – GlobeNewswire

Worldwide Dilated Cardiomyopathy (DCM) Market Insights, Epidemiology and Forecast – 2030 – ResearchAndMarkets.com – Business Wire

DUBLIN–(BUSINESS WIRE)–The “Dilated Cardiomyopathy (DCM) – Market Insights, Epidemiology and Market Forecast – 2030” drug pipelines report has been added to ResearchAndMarkets.com’s offering.

This report delivers an in-depth understanding of the Dilated Cardiomyopathy, historical and forecasted epidemiology as well as the Dilated Cardiomyopathy market trends in the United States, EU5 (Germany, France, Italy, Spain, and United Kingdom), and Japan.

The Dilated Cardiomyopathy market report provides current treatment practices, emerging drugs, Dilated Cardiomyopathy market share of the individual therapies, current and forecasted Dilated Cardiomyopathy market size from 2017 to 2030 segmented by seven major markets. The report also covers current Dilated Cardiomyopathy treatment practice/algorithm, market drivers, market barriers and unmet medical needs to curate best of the opportunities and assesses underlying potential of the market.

Epidemiology

The Dilated Cardiomyopathy epidemiology division provides the insights about historical and current Dilated Cardiomyopathy patient pool and forecasted trend for each seven major countries. It helps to recognize the causes of current and forecasted trends by exploring numerous studies and views of key opinion leaders. This part of the report also provides the diagnosed patient pool and their trends along with assumptions undertaken.

The disease epidemiology covered in the report provides historical as well as forecasted Dilated Cardiomyopathy epidemiology segmented as [Total Prevalent Population of Dilated Cardiomyopathy, Total Diagnosed Population of Dilated Cardiomyopathy, Familial and non-familial cases of Dilated Cardiomyopathy, Gender-Specific Cases of Dilated Cardiomyopathy, and Total Treated Cases of Dilated Cardiomyopathy] scenario of Dilated Cardiomyopathy in the 7MM covering the United States, EU5 countries (Germany, France, Italy, Spain, and United Kingdom), and Japan from 2017 to 2030.

Key Findings

Drug Chapters

Drug chapter segment of the Dilated Cardiomyopathy report encloses the detailed analysis of Dilated Cardiomyopathy marketed drugs and late stage (Phase-III and Phase-II) pipeline drugs. It also helps to understand the Dilated Cardiomyopathy clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, advantages and disadvantages of each included drug and the latest news and press releases.

Approved Drug

Corlanor (ivabradine): Amgen

Corlanor (ivabradine) is a hyperpolarization-activated cyclic nucleotide-gated channel blocker that reduces the spontaneous pacemaker activity of the cardiac sinus node by selectively inhibiting the If current, resulting in heart rate reduction with no effect on ventricular repolarization and no effects on myocardial contractility.

The US FDA approval of Corlanor (ivabradine) for the treatment of stable symptomatic heart failure (HF) due to dilated cardiomyopathy in pediatric patients aged 6 months to 18 years was based on a randomized, double-blind, placebo-controlled trial in 116 patients aged 6 months to less than 18 years with symptomatic DCM in sinus rhythm, NYHA/Ross class II to IV HF, and left ventricular ejection fraction 45%. The primary endpoint of the study was 20% reduction in resting heart rate from baseline without bradycardia or symptoms after an initial titration period.

Emerging Drugs

PF-07265803/ARRY-371797/ARRY-797: Pfizer

ARRY-371797 which is also known as ARRY-797 is an oral, p38 mitogen activated protein kinase (MAPK) inhibitor discovered by Array scientists. Compared to other p38 MAPK inhibitors ARRY-797 has unique and differentiated properties: it is highly selective, retains exceptional potency in whole blood and possesses a favorable pharmacokinetic profile. It is currently under phase III trial for the treatment of patients affected with dilated cardiomyopathy due to a Lamin A/C gene mutation. In the year 2019, Pfizer completed the acquisition of Array Biopharma to expand its pipeline and currently this drug is in phase III pipeline drugs of Pfizer with name PF-07265803 for the treatment of patients affected by dilated cardiomyopathy.

Ixmyelocel-T: Vericel

Ixmyelocel-T is an investigational autologous expanded multicellular therapy manufactured from the patient’s own bone marrow using Vericel’s proprietary, highly automated, fully closed cell-processing system. This process selectively expands the population of mesenchymal stromal cells and alternatively activated macrophages, which are responsible for production of anti-inflammatory and pro-angiogenic factors known to be important for repair of damaged tissue. Ixmyelocel-T has been designated as an orphan drug by the U.S. Food and Drug Administration for use in the treatment of DCM. However, currently the development of this drug is at halt because as per the recent news the company do not have current plans to initiate or fund a phase III trial for this drug at their own.

BC007: Berlin Cures GmbH

BC007 is a DNA aptamer-based compound that binds to and eliminates pathogenic autoantibodies directed against the beta-1 adrenoceptor, a receptor belonging to the large family of cell surface receptors known as G-protein coupled receptors that regulate the heart’s rate and contraction strength.

Ifetroban: Cumberland Pharmaceuticals

Ifetroban is a potent and selective inhibitor of the thromboxane receptor (TPr), preventing fibrosis and an inflammatory response. It was initially developed by Bristol-Myers Squibb as an anti-platelet agent to prevent blood clots (blood thrombus), and was acquired by Cumberland in 2011. It is believed that this drug molecule is able to stop important molecular signals that mediate inflammation and fibrosis (tissue scaring) mechanisms in the heart, triggered by the loss of dystrophin protein.

Danicamtiv/MYK-491: MyoKardia

MYK-491 is an orally-administered small molecule designed to increase the number of myosin-actin cross-bridges formed during cardiac muscle contraction while having minimal impact on diastolic function. In the heart, myosin is the motor protein that binds to actin to generate the force and movement of contraction. In patients with dilated cardiomyopathy and systolic heart failure, in which the left ventricle of the heart is too distended and weak to adequately pump blood to meet the body’s needs, MYK-491 is intended to increase myosin-actin engagement, thereby targeting the biomechanical defects underlying disease and improving cardiac contractility.

CAP-1002: Capricor Therapeutics

CAP-1002, Capricor’s lead product candidate, is a proprietary allogeneic adult stem cell therapy for the treatment of heart disease. The product is derived from donor heart tissue. The cells are expanded in the laboratory using a specialized process and then introduced directly into a patient’s heart via infusion into a coronary artery using standard cardiac catheterization techniques. CAP-1002 consists of allogeneic cardiosphere-derived cells, or CDCs, a unique population of cells that has been shown to exert potent immunomodulatory activity and alters the immune system’s activity to encourage cellular regeneration.

Market Outlook

Besides treating any recognizable and reversible underlying causes, the management and treatment of DCM are in concordance with the standard heart failure guidelines. Currently, the treatment pattern of DCM is mainly dependent on pharmacological therapy, pacing therapy, surgical options, and Corlanor (ivabradine).

The pharmacological therapies consist of diuretics, inotropic agents, afterload reducing agents, beta-blockers, anticoagulation medications, anti-arrhythmia medications. The main diuretics that are prescribed for the treatment are furosemide, spironolactone, bumetanide, and metolazone. Common side effects of diuretics include dehydration and abnormalities in the blood chemistries particularly potassium loss. Inotopric agents that are prescribed for the treatment are digoxin, dobutamine, dopamine, epinephrine, norepinephrine, vasopressin, and milrinone. Some afterload reducing medications include angiotensin-converting enzyme inhibitors (ACE inhibitors) such as captopril, enalMay, lisinopril, monopril, angiotensin I blocker such as losartan. Losartan and milrinone are inotropic agents that also relax the arteries. Stronger anticoagulation drugs are warfarin, heparin, and enoxaparin; these drugs require careful monitoring with regular blood testing.

Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) have shown benefit in the treatment of heart failure with reduced ejection fraction and are suggested for the patients affected with DCM. Aldosterone receptor blockade with spironolactone or eplerenone also is recommended in patients with New York Heart Association (NYHA) heart failure class II-IV and systolic dysfunction. Similarly, beta-blockade with carvedilol, bisoprolol, or long-acting metoprolol is recommended in all patients with heart failure with reduced ejection fraction without any contraindications. The addition of isosorbide dinitrate plus hydralazine also has shown to increase survival amongst those with advanced disease.

In some cases, beta-blockers allow an enlarged heart to become more normal in size. Common beta-blockers include carvedilol, metoprolol, propranolol, and atenolol. Side effects include dizziness, low heart rate, low blood pressure, and, in some cases, fluid retention, fatigue, impaired school performance, and depression. The choice of anticoagulation drugs depends on how likely it is that a blood clot will form. Less strong anticoagulation medications include aspirin and dipyridamole. Common anti-arrhythmia medications include amiodarone, procainamide, and lidocaine. Also, Corlanor (ivabradine) is an approved therapy for the treatment of 6 months to 18 years old patient affected by Dilated Cardiomyopathy.

Key Findings

According to the report, Dilated Cardiomyopathy market in the 7MM is expected to change in the study period 2017-2030. The total therapeutic market of Dilated Cardiomyopathy in seven major markets was found to be USD 244 million in 2017 which is expected to increase during the study period (2017-2030).

The United States Market Outlook

In 2017, the total market size of Dilated Cardiomyopathy therapies was estimated to be USD 142.9 million in the United States which is expected to increase in the study period (2017-2030).

EU5 Countries: Market Outlook

In 2017, the total market size of Dilated Cardiomyopathy therapies was found to be USD 74.4 million in the EU5 countries which is expected to increase in the study period (2017-2030).

Japan Market Outlook

The total market size of Dilated Cardiomyopathy therapies in Japan was found to be USD 27.1 million in 2017 which is also expected to increase during the study period (2017-2030).

Pipeline Development Activities

The drugs which are in pipeline include:

1. PF-07265803/ARRY-371797/ARRY-797: Pfizer

2. Ixmyelocel-T: Vericel

3. BC007: Berlin Cures GmbH

4. Ifetroban: Cumberland Pharmaceuticals

5. Danicamtiv/MYK-491: MyoKardia

6. CAP-1002: Capricor Therapeutics

Access and Reimbursement Scenario

The record published in United HealthCare Services, in the United States, stated that reimbursement is eligible for the CPT codes related to various genetic testing for cardiac disease. CPT code 81439 includes indications such as hereditary cardiomyopathy (e.g., hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy), genomic sequence analysis panel – must include sequencing of at least five cardiomyopathy-related genes (e.g., DSG2, MYBPC3, MYH7, PKP2, TTN). Moreover, cardiomyopathies that present primarily as neuromuscular disorders and related genetic testing are also covered in the Medical Policy.

KOL Views

To keep up with current market trends, we take KOL’s and SME’s opinion working in Dilated Cardiomyopathy domain through primary research to fill the data gaps and validates our secondary research. Their opinion helps to understand and validate current and emerging therapies treatment patterns and Dilated Cardiomyopathy market trend. This will support the clients in the introduction of potential upcoming novel treatment by identifying the overall scenario of the market and the unmet needs.

Competitive Intelligence Analysis

The publisher performs Competitive and Market Intelligence analysis of the Dilated Cardiomyopathy Market by using various Competitive Intelligence tools that includes – SWOT analysis, PESTLE analysis, Porter’s five forces, BCG Matrix, Market entry strategies etc. The inclusion of the analysis entirely depends upon the data availability.

Scope of the Report

Report Highlights

Companies Mentioned

For more information about this drug pipelines report visit https://www.researchandmarkets.com/r/qfjown

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Worldwide Dilated Cardiomyopathy (DCM) Market Insights, Epidemiology and Forecast – 2030 – ResearchAndMarkets.com – Business Wire

Genmab Announces Janssen Granted U.S. FDA Approval for DARZALEX (daratumumab) in Combination with Carfilzomib and Dexamethasone in Relapsed or…

August 20, 2020 16:40 ET | Source: Genmab A/S

Company Announcement

Copenhagen, Denmark; August 20, 2020 Genmab A/S (Nasdaq: GMAB) announced today that the U.S. Food and Drug Administration (U.S. FDA) has approved the use of DARZALEX (daratumumab) in combination with carfilzomib and dexamethasone (DKd) for the treatment of adult patients with relapsed/refractory multiple myeloma who have received one to three previous lines of therapy. A supplemental Biologics License Application (sBLA) for this indication was submitted by Genmabs licensing partner, Janssen Biotech, Inc. (Janssen), in February 2020. In August 2012, Genmab granted Janssen an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

We are extremely pleased that multiple myeloma patients in the U.S. will now have yet another treatment option as this is the eighth overall U.S. FDA approval for DARZALEX and the fifth in the relapsed/refractory setting. In addition, DARZALEX is now the first CD38 antibody approved for use in combination with carfilzomib, said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The combination has been approved in two carfilzomib dosing regimens, 70 mg/m2 once weekly and 56 mg/m2 twice weekly, based on positive results from the Phase 3 CANDOR and Phase 1b EQUULEUS studies. CANDOR was an Amgen-sponsored study, co-funded by Janssen Research & Development, LLC. EQUULEUS was sponsored by Janssen Research & Development, LLC.

About the CANDOR study The Phase 3 trial (NCT03158688) was a randomized, open-label study that included 466 patients with multiple myeloma who had relapsed after 1 to 3 prior therapies. Patients were randomized to receive either DKd or carfilzomib and dexamethasone (Kd) alone. In the daratumumab treatment arm, patients received 8 milligrams per kilogram (mg/kg) on days 1 and 2 of cycle 1, then 16 mg/kg once weekly for the remaining doses of the first 2 cycles, then every 2 weeks for 4 cycles (cycles 3 to 6), and then every 4 weeks for the remaining cycles or until disease progression. In both treatment arms carfilzomib was dosed twice weekly (20 mg/m2 on cycle 1 days 1 and 2 and 56 mg/m2 beginning on cycle 1 day 8 and thereafter) and dexamethasone was given weekly (40 mg orally or via IV infusion). The primary endpoint of the study was progression free survival (PFS).

About the EQUULEUS (MMY1001) Study The Phase 1b EQUULEUS (NCT01998971) study was an open label, multi-cohort trial that evaluated the safety, tolerability, and dose regimen of daratumumab when administered in combination with various treatment regimens for the treatment of multiple myeloma. Among the regiments evaluated, the combination of DKd compared to Kd alone was studied in 85 patients with relapsed/refractory multiple myeloma who had received one to three prior lines of therapy using a once-weekly dosing regimen. DKd was evaluated at a starting dose of 20 mg/m2, which was increased to 70 mg/m2 on Cycle 1, Day 8 and onward.

About multiple myeloma Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 26,000 new patients were expected to be diagnosed with multiple myeloma and approximately 13,650 people were expected to die from the disease in the U.S. in 2018.3 Globally, it was estimated that 160,000 people were diagnosed and 106,000 died from the disease in 2018.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5

About DARZALEX(daratumumab) DARZALEX (daratumumab) has become a backbone therapy in the treatment of multiple myeloma. DARZALEX intravenous infusion is indicated for the treatment of adult patients in the United States: in combination with carfilzomib and dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma who have received one to three previous lines of therapy; in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.6 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma.

DARZALEX is indicated for the treatment of adult patients in Europe via intravenous infusion or subcutaneous administration: in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy7. Daratumumab is the first subcutaneous CD38 antibody approved in Europe for the treatment of multiple myeloma. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S.

In Japan, DARZALEX intravenous infusion is approved for the treatment of adult patients: in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone for the treatment of relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United States, Europe and Japan. For more information, visit www.DARZALEX.com.

DARZALEX FASPRO (daratumumab and hyaluronidase-fihj), a subcutaneous formulation of daratumumab, is approved in the United States for the treatment of adult patients with multiple myeloma: in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for ASCT; in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for ASCT and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy; in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy; and as monotherapy, in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.8 DARZALEX FASPRO is the first subcutaneous CD38 antibody approved in the U.S. for the treatment of multiple myeloma.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a persons own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).6,9,10,11,12

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and refractory and frontline multiple myeloma settings. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases in which CD38 is expressed, such as amyloidosis and T-cell acute lymphocytic leukemia (ALL). Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA for certain indications of multiple myeloma, including as a monotherapy for heavily pretreated multiple myeloma and in combination with certain other therapies for second-line treatment of multiple myeloma.

About Genmab Genmab is a publicly traded, international biotechnology company specializing in the creation and development of differentiated antibody therapeutics for the treatment of cancer. Founded in 1999, the company is the creator of the following approved antibodies: DARZALEX (daratumumab, under agreement with Janssen Biotech, Inc.) for the treatment of certain multiple myeloma indications in territories including the U.S., Europe and Japan, Kesimpta (subcutaneous ofatumumab, under agreement with Novartis AG), for the treatment of adults with relapsing forms of multiple sclerosis in the U.S. and TEPEZZA (teprotumumab, under agreement with Roche granting sublicense to Horizon Therapeutics plc) for the treatment of thyroid eye disease in the U.S. A subcutaneous formulation of daratumumab, known as DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) in the U.S., has been approved in the U.S. and Europe for the treatment of adult patients with certain multiple myeloma indications. The first approved Genmab created therapy, Arzerra (ofatumumab, under agreement with Novartis AG), approved for the treatment of certain chronic lymphocytic leukemia indications, is available in Japan and is also available in other territories via compassionate use or oncology access programs. Daratumumab is in clinical development by Janssen for the treatment of additional multiple myeloma indications, other blood cancers and amyloidosis. Genmab also has a broad clinical and pre-clinical product pipeline. Genmab’s technology base consists of validated and proprietary next generation antibody technologies – the DuoBody platform for generation of bispecific antibodies, the HexaBody platform, which creates effector function enhanced antibodies, the HexElect platform, which combines two co-dependently acting HexaBody molecules to introduce selectivity while maximizing therapeutic potency and the DuoHexaBody platform, which enhances the potential potency of bispecific antibodies through hexamerization. The company intends to leverage these technologies to create opportunities for full or co-ownership of future products. Genmab has alliances with top tier pharmaceutical and biotechnology companies. Genmab is headquartered in Copenhagen, Denmark with sites in Utrecht, the Netherlands, Princeton, New Jersey, U.S. and Tokyo, Japan.

Contact: Marisol Peron, Corporate Vice President, Communications & Investor Relations T: +1 609 524 0065; E: mmp@genmab.com

For Investor Relations: Andrew Carlsen, Senior Director, Investor Relations T: +45 3377 9558; E: acn@genmab.com

This Company Announcement contains forward looking statements. The words believe, expect, anticipate, intend and plan and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with pre-clinical and clinical development of products, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products or technologies obsolete, and other factors. For a further discussion of these risks, please refer to the risk management sections in Genmabs most recent financial reports, which are available on www.genmab.com and the risk factors included in Genmabs most recent Annual Report on Form 20-F and other filings with the U.S. Securities and Exchange Commission (SEC), which are available at www.sec.gov. Genmab does not undertake any obligation to update or revise forward looking statements in this Company Announcement nor to confirm such statements to reflect subsequent events or circumstances after the date made or in relation to actual results, unless required by law.

Genmab A/S and/or its subsidiaries own the following trademarks: Genmab; the Y-shaped Genmab logo; Genmab in combination with the Y-shaped Genmab logo; HuMax; DuoBody; DuoBody in combination with the DuoBody logo; HexaBody; HexaBody in combination with the HexaBody logo; DuoHexaBody; HexElect; and UniBody. Arzerra and Kesimpta are trademarks of Novartis AG or its affiliates. DARZALEX and DARZALEX FASPRO are trademarks of Janssen Pharmaceutica NV. TEPEZZA is a trademark of Horizon Therapeutics plc.

1 American Cancer Society. “Multiple Myeloma Overview.” Available at http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma.Accessed June 2016. 2 National Cancer Institute. “A Snapshot of Myeloma.” Available at www.cancer.gov/research/progress/snapshots/myeloma. Accessed June 2016. 3 Globocan 2018. United States of America Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/840-united-states-of-america-fact-sheets.pdf. 4 Globocan 2018. World Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed December 2018. 5 American Cancer Society. “How is Multiple Myeloma Diagnosed?” http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed June 2016 6 DARZALEX Prescribing information, September 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761036s024lbl.pdf Last accessed September 2019 7 DARZALEX Summary of Product Characteristics, available at https://www.ema.europa.eu/en/medicines/human/EPAR/darzalex Last accessed June 2020 8 DARZALEX FASPRO Prescribing information, May 2020. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761145s000lbl.pdf Last accessed May 2020 9 De Weers, M et al. Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors. The Journal of Immunology. 2011; 186: 1840-1848. 10 Overdijk, MB, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 2015; 7: 311-21. 11 Krejcik, MD et al. Daratumumab Depletes CD38+ Immune-regulatory Cells, Promotes T-cell Expansion, and Skews T-cell Repertoire in Multiple Myeloma. Blood. 2016; 128: 384-94. 12 Jansen, JH et al. Daratumumab, a human CD38 antibody induces apoptosis of myeloma tumor cells via Fc receptor-mediated crosslinking.Blood. 2012; 120(21): abstract 2974.

Company Announcement no. 38 CVR no. 2102 3884 LEI Code 529900MTJPDPE4MHJ122

Genmab A/S Kalvebod Brygge 43 1560 Copenhagen V Denmark

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Genmab Announces Janssen Granted U.S. FDA Approval for DARZALEX (daratumumab) in Combination with Carfilzomib and Dexamethasone in Relapsed or…

Huntington’s Disease Alters Human Development in the Fetal… : Neurology Today – LWW Journals

By Jamie Talan August 20, 2020 The Science Explained Article In Brief

Scientists identified several cellular abnormalities in the developing cortex from fetal tissues carrying the mutant gene implicated in Huntington’s disease. The findings suggest that the disease alters human development at an early age.

Teams of French researchers have found cellular changes that alter cortical development in the brains of human fetuses who carry the mutant huntingtin gene (mHTT) implicated in Huntington’s disease (HD).

The finding adds a new wrinkle to the puzzle of HD as many people who carry the mutation can live healthy lives for four decades or longer before the onset of symptoms.

No one knows why, but this is a common thread in other late-onset genetically-driven neurodegenerative conditions like Alzheimer’s and Parkinson’s disease, the researchers said. And a growing number of researchers believe that it is best to treat people with the HD mutation as early as possible.Now, findings from this study, published online July 16 in Science, beg the question: How early?

The researchers, led by Sandrine Humbert, PhD, research director of INSERM (the French National Institute for Health and Medical Research) and group leader at the Grenoble Institut des Neurosciences, and Alexandra Durr, MD, PhD, professor at Sorbonne University and team leader of the Paris Brain Institute at Pitie-Salptrire Hospital, had access to fetal tissue from families that terminated their pregnancy in the context of a prenatal test. The developing fetus carried the mHTT.

Other mouse and neuroimaging studies with pre-manifest mutation carriers have suggested that the mutation might affect neurodevelopment but this is the first time that scientists have looked to the human fetus to know for sure.

Dr. Durr works with people undergoing genetic testing and counseling for Huntington’s disease. Her team was able to collect cortical tissue from four HD mutation carriers when the pregnancies were terminated at around 13-weeks’ gestation and tissue from four healthy controls.

This age is an opportune time to assess the tissue, the study authors noted, because at this stage the cortical neurons that project to the striatumthose that become dysfunctional and die during the course of the diseaseare being born from progenitor cells at the ventricular zone.

Thirteen weeks gestation is the time point when you need a lot of cells to be generated, Dr. Humbert explained. At this stage in development cells are massively cycling. The implications for the fetal brain with an HD mutation is that there is a shift to differentiate early and, as a result, you generate fewer neurons, at least at this specific time point during development.

The scientists identified several cellular abnormalities in the developing cortex, including mislocalization of the mutant huntingtin protein and other junction proteins that keep the neuroepithelium sealed. They observed abnormal ciliogenesis and changes in mitosis and cell-cycle progression, which correlated with defects in the balance between renewal and differentiation of progenitors.

In neuroprogenitor cells, this balance is tightly regulated to provide the right amount of neurons along the development of the cortex. Fewer proliferating cells and more progenitors prematurely began to differentiate in the tissues of HD carrierssubtle findings that are changing the landscape of the cortex.

Huntington’s definitely has a neurodevelopmental component in addition to a neurodegenerative disease, Dr. Humbert explained. Studies in mice have found similar cellular abnormalities.

These data are supported by similar findings in mice that show mutant HTT impairs neuroprogenitor cell division, migration, and maturation, and that these changes result in a thinner cortex. Additional studies have revealed that early exposure to mutant HTT is enough to trigger signs of HD when the mice grow up. Neuroimaging studies with pre-symptomatic mutation carriers, even children, have shown smaller intracranial volume in HD mutation carriers.

What is also intriguing is that these events occurred even though the fetuses had small pathological expansions39, 40, and 42 repeats that would typically cause an adult onset of HD.

The findings trigger a number of questions: Why aren’t there any obvious clinical problems until mid-life? Do these early developmental changes set the stage for symptoms decades down the road? Are other brain cells compensating for the changes and it takes 40-plus years for symptoms to develop?

Dr. Humbert and her colleagues said that the defects we observed likely render the cortico-striatal circuitry more vulnerable to the later dysfunctions characteristic of HD. The path to degeneration is complex, however, and weaves together both pathogenic and compensatory mechanisms.

They cited a recent pair of studies in Neurology by Peg Nopoulos, MD, and her colleagues at the University of Iowa, Carver College of Medicine that looked at children who are HD mutation carriers. They showed initial striatal enlargement with hyper-connectivity between the striatum and the cerebellum. Over time, the striatum decreases and the connections weaken. Although the cerebellar connections initially may help compensate for the abnormally developed striatum, it is the loss of these connections that may ultimately lead to motor abnormalities. Again, it will be decades before any obvious motor signs develop.

Once there are disease-modifying therapies, we know we should treat as early as possible or differently in pre-manifest compared to symptomatic stages of the disease, or it may not be sufficient, said Dr. Humbert.

She said she is now interested in understanding how these early defects contribute to adult pathology, and how their compensation could be regulated during the silent symptom-free period. This should give access to new molecules of interest, either as treatments or biomarkers, she added.

It is a beautiful paper, said Christopher A. Ross, MD, PhD, director of neurobiology and professor of psychiatry and behavioral sciences at Johns Hopkins Medicine. The concept fits with ideas people have had. Their study is groundbreaking.

It’s unclear how these cell-cycle abnormalities alter normal development, said Dr. Ross. I have been doing pre-manifest genetic testing for years, and my belief is that asymptomatic people who are far from their predicted onset but test positive are clinically completely normal.

These data are very interesting, said Sarah Tabrizi, MD, PhD, professor of clinical neurology at University College London Institute of Neurology. There has been debate in the HD field regarding the existence of a neurodevelopmental deficit, and evidence is accruing that this may be the case based on differentiating HD induced pluripotent stem cell systems, mouse development, and now these studies of early human development.

We recently found that HD gene carriers ~24 years before predicted disease onset had essentially completely normal brains including normal cortico-striatal connectivity on advanced neuroimaging, apart from a slightly smaller striatum, which we hypothesized resulted in selective vulnerability of the striatum to subsequent neurodegeneration in HD (Lancet Neurology 2020). Importantly, our HD gene carriers performed as well as matched controls on a range of stringent cognitive and motor assessments.

This all suggests that we need to treat as early as possible with disease-modifying therapies to enable us to delay or prevent symptom onset, Dr. Tabrizi said, and means that there is still great potential for therapies to potentially prevent the neurodegeneration occurring if we treat early enough. We need to understand more about the very earliest manifestations of neurodegeneration and then intervene at the optimal stage.

Dr. Ross believes that the brain figures out a workaround of these developmental alterations but agrees that it may leave the brain more vulnerable later in life. He added, These findings are conceptually very important, though not necessarily with immediate implications for patients or those who are asymptomatic but test positive.

He said that this finding represents a paradigm shift that will lead scientists to look for developmental abnormalities in other neurodegenerative diseases.

It is important to emphasize how the Huntington gene (HTT) affects the brain in the context of a lifetime trajectory, added Dr. Nopoulos, the Paul W. Penningroth professor of psychiatry and chair in the department of psychiatry at University of Iowa Carver College of Medicine. This gene is vital for brain development. Our group has shown that HTT drives brain development and that repeats in HTT are beneficial, and the higher the repeat, the higher the IQ. For individuals with repeats in the range of 39-42, like those in the fetal tissue study, HTT likely contributed to the development of a cerebellar-striatal-cortical circuit that was initially advantageous (which is why they are found to be asymptomatic in the Tabrizi study), but later in life, vulnerable to degeneration. Therefore, although the findings in the fetal tissue study are reported as abnormalities, they are more likely to be evidence of differences since the changes are not pathologic until much later in life.

However, she added, everything about HTT is on a spectrumthe classic dose effect of repeats on the age of onset is a good example where greater repeats result in earlier onset. The same is likely true for development.

Human brain development is prolonged, lasting until roughly age 30, she continued. Those with repeats in the low mutant range (36-42) will have a chance for full brain development before the vulnerable cerebellar-striatal-cortical circuit begins to degenerate and disease manifests. However, in those with longer repeats (above 50), the vulnerable brain circuit may begin to degenerate before full brain maturation is complete.

In this range of repeats, the ultimate effect of mHTT on brain development may be detrimental. These considerations are vitally important when considering when to intervene with preventive therapies such as gene knock-down drugs. In those with low mutant repeats, knocking down the gene early in life (before age 30) may be detrimental to brain development, yet in those with high repeats, rescue may need to be much earlier (adolescence).

Drs. Humbert, Durr, Ross, and Nopoulos had no relevant disclosures.

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Huntington’s Disease Alters Human Development in the Fetal… : Neurology Today – LWW Journals

Researchers find method to regrow cartilage in the joints – Stanford Medical Center Report

Damaged cartilage can be treated through a technique called microfracture, in which tiny holes are drilled in the surface of a joint. The microfracture technique prompts the body to create new tissue in the joint, but the new tissue is not much like cartilage.

Microfracture results in what is called fibrocartilage, which is really more like scar tissue than natural cartilage, said Chan. It covers the bone and is better than nothing, but it doesnt have the bounce and elasticity of natural cartilage, and it tends to degrade relatively quickly.

The most recent research arose, in part, through the work of surgeon Matthew Murphy, PhD, a visiting researcher at Stanford who is now at the University of Manchester. I never felt anyone really understood how microfracture really worked, Murphy said. I realized the only way to understand the process was to look at what stem cells are doing after microfracture. Murphy is the lead author on the paper. Chan and Longaker are co-senior authors.

For a long time, Chan said, people assumed that adult cartilage did not regenerate after injury because the tissue did not have many skeletal stem cells that could be activated. Working in a mouse model, the team documented that microfracture did activate skeletal stem cells. Left to their own devices, however, those activated skeletal stem cells regenerated fibrocartilage in the joint.

But what if the healing process after microfracture could be steered toward development of cartilage and away from fibrocartilage? The researchers knew that as bone develops, cells must first go through a cartilage stage before turning into bone. They had the idea that they might encourage the skeletal stem cells in the joint to start along a path toward becoming bone, but stop the process at the cartilage stage.

The researchers used a powerful molecule called bone morphogenetic protein 2 (BMP2) to initiate bone formation after microfracture, but then stopped the process midway with a molecule that blocked another signaling molecule important in bone formation, called vascular endothelial growth factor (VEGF).

What we ended up with was cartilage that is made of the same sort of cells as natural cartilage with comparable mechanical properties, unlike the fibrocartilage that we usually get, Chan said. It also restored mobility to osteoarthritic mice and significantly reduced their pain.

As a proof of principle that this might also work in humans, the researchers transferred human tissue into mice that were bred to not reject the tissue, and were able to show that human skeletal stem cells could be steered toward bone development but stopped at the cartilage stage.

The next stage of research is to conduct similar experiments in larger animals before starting human clinical trials. Murphy points out that because of the difficulty in working with very small mouse joints, there might be some improvements to the system they could make as they move into relatively larger joints.

The first human clinical trials might be for people who have arthritis in their fingers and toes. We might start with small joints, and if that works we would move up to larger joints like knees, Murphy says. Right now, one of the most common surgeries for arthritis in the fingers is to have the bone at the base of the thumb taken out. In such cases we might try this to save the joint, and if it doesnt work we just take out the bone as we would have anyway. Theres a big potential for improvement, and the downside is that we would be back to where we were before.

Longaker points out that one advantage of their discovery is that the main components of a potential therapy are approved as safe and effective by the FDA. BMP2 has already been approved for helping bone heal, and VEGF inhibitors are already used as anti-cancer therapies, Longaker said. This would help speed the approval of any therapy we develop.

Joint replacement surgery has revolutionized how doctors treat arthritis and is very common: By age 80, 1 in 10 people will have a hip replacement and 1 in 20 will have a knee replaced. But such joint replacement is extremely invasive, has a limited lifespan and is performed only after arthritis hits and patients endure lasting pain. The researchers say they can envision a time when people are able to avoid getting arthritis in the first place by rejuvenating their cartilage in their joints before it is badly degraded.

One idea is to follow a Jiffy Lube model of cartilage replenishment, Longaker said. You dont wait for damage to accumulate you go in periodically and use this technique to boost your articular cartilage before you have a problem.

Longaker is the Deane P. and Louise Mitchell Professor in the School of Medicine and co-director of the Institute for Stem Cell Biology and Regenerative Medicine. Chan is a member of the Institute for Stem Cell Biology and Regenerative Medicine and Stanford Immunology.

Other Stanford scientist taking part in the research were professor of pathology Irving Weissman, MD, the Virginia and D. K. Ludwig Professor in Clinical Investigation in Cancer Research; professor of surgery Stuart B. Goodman, MD, the Robert L. and Mary Ellenburg Professor in Surgery; associate professor of orthopaedic surgery Fan Yang, PhD; professor of surgery Derrick C. Wan, MD; instructor in orthopaedic surgery Xinming Tong, PhD; postdoctoral research fellow Thomas H. Ambrosi, PhD; visiting postdoctoral scholar Liming Zhao, MD; life science research professionals Lauren S. Koepke and Holly Steininger; MD/PhD student Gunsagar S. Gulati, PhD; graduate student Malachia Y. Hoover; former student Owen Marecic; former medical student Yuting Wang, MD; and scanning probe microscopy laboratory manager Marcin P. Walkiewicz, PhD.

The research was supported by the National Institutes of Health (grants R00AG049958, R01 DE027323, R56 DE025597, R01 DE026730, R01 DE021683, R21 DE024230, U01HL099776, U24DE026914, R21 DE019274, NIGMS K08GM109105, NIH R01GM123069 and NIH1R01AR071379), the California Institute for Regenerative Medicine, the Oak Foundation, the Pitch Johnson Fund, the Gunn/Olivier Research Fund, the Stinehart/Reed Foundation, The Siebel Foundation, the Howard Hughes Medical Institute, the German Research Foundation, the PSRF National Endowment, National Center for Research Resources, the Prostate Cancer Research Foundation, the American Federation of Aging Research and the Arthritis National Research Foundation.

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Researchers find method to regrow cartilage in the joints – Stanford Medical Center Report