Blood Pressure and Prostate Treatment May Prevent or Slow Parkinson’s, Early Study Suggests – Parkinson’s News Today

People taking Hytrin (terazosin)or similar medications to treat high blood pressure and benign prostatic hyperplasiamay be less likely to develop Parkinsons disease, an early study suggests.

Parkinsons patients who use these medications may also see their disease progress more slowly and with fewer complications, its researchers report.

The study, Enhancing glycolysis attenuates Parkinsons disease progression in models and clinical databases, was published in the Journal of Clinical Investigation.

Hytrin is indicated for the treatment of non-cancerous prostate enlargement and high blood pressure (hypertension). The medication, available as a generic (terazosin), acts on the alpha-1 adrenergic receptor to block adrenalines action, relaxing smooth muscle in both the blood vessels and the prostate, allowing blood and urine, respectively, to flow more easily.

Experts agree that energy metabolism plays a central role in the molecular mechanism of neurodegenerative diseases like Parkinsons. In fact, problems in energy metabolism and low levels of cellular energy are common features of this disorder.

Hytrin has been shown to enhance the activity of a protein called phosphoglycerate kinase 1 (PGK1), which is involved in a critical energy-producing process known as glycolysis, where the simple sugar glucose is broken down by cells to produce energy. Boosting PGK1 activity increases the number of energy molecules, also known as ATP, within a cell.

Because low levels of ATP have been observed in Parkinsons, increasing the breakdown of glucose and hence cellular energy, in theory, may slow down or prevent the neurodegenerative processes underlying this disease.

Researchers at Capital Medical University in Beijing, decided to test this hypothesis and investigate whether increasing PGK1 activity levels would change the course of Parkinsons disease.

Hytrin was found to increase brain ATP levels and slow or prevent nerve cell loss in several models of Parkinsons (MPTP, rotenone and 6-OHDA-induced or genetic models): mice, rats, flies, and induced pluripotent stem cells. MPTP, rotenone and 6-OHDA are all neurotoxins that induce death of dopamine-producing neurons and mimic Parkinsons symptoms.

Treatment with this medication increased brain dopamine levels the chemical messenger that is present in low levels in the brains of Parkinsons patients and partially restored motor function in both mice and flies.

Importantly, boosting PGK1 activity was beneficial even when treatment was initiated after the onset of neurodegeneration, suggesting the modulation of this proteins function could help to slow Parkinsons progression.

Because Hytrin is prescribed for other diseases, scientists also studied two human databases the Parkinsons Progression Markers Initiative and the IBM Watson/Truven database looking for a possible Hytrin effect in relation to Parkinsons disease.

These two data sets included a total of 4,072 individuals on Hytrin, doxazosin, or alfuzosin. The latter two medications produce effects similar to those of Hytrin.

A retrospective analysis on both databases revealed that use of Hytrin and related agents slowed Parkinsons disease progression, reduced the number of neurodegeneration-related complications, and lessened the risk of a Parkinsons diagnosis, compared to people not using these medications.

These findings identify a protein and a pathway that might be targeted to slow or prevent neurodegeneration in PD [Parkinsons disease] and potentially other neurodegenerative diseases with altered energy balance, the researchers concluded.

Terazosin, available only by prescription, can cause dizziness and fainting because it lowers blood pressure.

With over three years of experience in the medical communications business, Catarina holds a BSc. in Biomedical Sciences and a MSc. in Neurosciences. Apart from writing, she has been involved in patient-oriented translational and clinical research.

View post:
Blood Pressure and Prostate Treatment May Prevent or Slow Parkinson's, Early Study Suggests - Parkinson's News Today

New Gene Editing Technique Shown to Correct COL7A1 Gene in RDEB Cells – Epidermolysis Bullosa News

A novel gene editing technique was able to correct mutations inCOL7A1 in cells taken from people with recessive dystrophic epidermolysis bullosa (RDEB), providing a proof of concept for using the editing technique in the disease.

The finding was published in theJournal of Investigative Dermatology in a study titled, Base editor correction of COL7A1 in recessive dystrophic epidermolysis bullosa patient-derived fibroblasts and iPSCs.

The idea behind gene editing is simple: If a disease (such as RDEB) is caused by a mutation in a gene (COL7A1), then changing the genetic code to remove the mutation should functionally cure the disease. Of course, rewriting genetic code in living cells much less in human beings is far from simple.

Most current lab techniques basically involve cutting out the section of DNA that has the mutation, then replacing it with a healthy version. The problem is that there are often small insertions or deletions in the code where the DNA is cut, which isnt desirable.

In the new study, researchers tested a novel editing technique that uses a lab-made protein called an adenine base editor (ABE) to change just one nucleotide (a letter in the DNA code) without the need to cut out a whole chunk of DNA.

The researchers tried using ABE to correct mutations in COL7A1in skin cells taken from two RDEB patients. Broadly, they were successful, correcting the mutation in the DNA in about 24% of the cells; these cells also expressed collagen type VII (C7), the protein encoded by COL7A1.

The researchers then used the corrected skin cells to generate induced pluripotent stem cells (iPSCs, a type of cell that will perpetually divide and that, through chemical cues, can be led to differentiate into many different cell types). These iPSCs still expressed C7, providing a proof of concept that could be helpful in translating these findings into patients.

The researchers also surveyed other spots in the cells genomes to see whether there were any places the ABE was making changes it wasnt intended to. They didnt find any, suggesting a fairly low off-target rate.

Collectively, our study shows the feasibility of autologous cellular engineering using base editing to correct COL7A1 mutations in cell populations currently employed clinically for RDEB, the researchers concluded.

Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.

Total Posts: 12

Ins Martins holds a BSc in Cell and Molecular Biology from Universidade Nova de Lisboa and is currently finishing her PhD in Biomedical Sciences at Universidade de Lisboa. Her work has been focused on blood vessels and their role in both hematopoiesis and cancer development.

Read the rest here:
New Gene Editing Technique Shown to Correct COL7A1 Gene in RDEB Cells - Epidermolysis Bullosa News

Vaginitis Therapeutics Market Overview with Detailed Analysis, Competitive lands – News By ReportsGO

The ' Vaginitis Therapeutics market' research report added by Market Study Report, LLC, is an in-depth analysis of the latest trends persuading the business outlook. The report also offers a concise summary of statistics, market valuation, and profit forecast, along with elucidating paradigms of the evolving competitive environment and business strategies enforced by the behemoths of this industry.

The latest research study on the Vaginitis Therapeutics market is a pivotal collection of insights pertaining to this industry vertical, with respect to certain parameters. The research report focuses on providing an in-depth synopsis of this industry, specifically illuminating the market industry size and share, application bifurcation, product types, as well as novel opportunities in the business space.

Request a sample Report of Vaginitis Therapeutics Market at:https://www.marketstudyreport.com/request-a-sample/1984739?utm_source=reportsgo.com&utm_medium=sp

Important insights pertaining to some of the major vendors in this industry are encompassed in the report. In addition, details have been given about the regions which have accrued the maximum returns. In essence, the study on the Vaginitis Therapeutics market plans to deliver a highly segmented overview of this industry, with respect to its present and future scenarios.

How will the report be helpful for the established stakeholders and new entrants

Driving Forces as well as Challenges of the Vaginitis Therapeutics market: How does the study elaborate on the same

Ask for Discount on Vaginitis Therapeutics Market Report at:https://www.marketstudyreport.com/check-for-discount/1984739?utm_source=reportsgo.com&utm_medium=sp

The geographical spectrum of the business as well as its influence on the overall Vaginitis Therapeutics market outlook:

A brief overview of the Vaginitis Therapeutics market breakdown:

For More Details On this Report: https://www.marketstudyreport.com/reports/global-vaginitis-therapeutics-market-growth-2019-2024

Some of the Major Highlights of TOC covers:

Executive Summary

Manufacturing Cost Structure Analysis

Development and Manufacturing Plants Analysis of Vaginitis Therapeutics

Key Figures of Major Manufacturers

Related Reports:

1. Global Induced Pluripotent Stem Cells (iPSCs) Market Growth (Status and Outlook) 2019-2024This report includes the assessment of Induced Pluripotent Stem Cells (iPSCs) market size for value and volume. Both top-down and bottom-up approaches have been used to estimate and validate the Induced Pluripotent Stem Cells (iPSCs) market, to estimate the size of various other dependent submarkets in the overall market.Read More: https://www.marketstudyreport.com/reports/global-induced-pluripotent-stem-cells-ipscs-market-growth-status-and-outlook-2019-2024

2. Global Veterinary Cephalosporin Market Growth 2019-2024Veterinary Cephalosporin Market Report covers a valuable source of perceptive information for business strategists. Veterinary Cephalosporin Industry provides the overview with growth analysis and historical & futuristic cost, revenue, demand and supply data (as applicable). The research analysts provide an elegant description of the value chain and its distributor analysis.Read More: https://www.marketstudyreport.com/reports/global-veterinary-cephalosporin-market-growth-2019-2024

Read More Reports On: https://www.marketwatch.com/press-release/at-5-cagr-steel-roofing-market-size-is-expected-to-exhibit-us-10000-million-by-2025-2019-09-19

Contact Us:Corporate Sales,Market Study Report LLCPhone: 1-302-273-0910Toll Free: 1-866-764-2150 Email: [emailprotected]

See the rest here:
Vaginitis Therapeutics Market Overview with Detailed Analysis, Competitive lands - News By ReportsGO

Efavirenz/Tenofovir/Emtricitabine Combination Drug Market Overview with Detailed – News by Intelligence Journal

The ' Efavirenz/Tenofovir/Emtricitabine Combination Drug market' research report added by Market Study Report, LLC, is an in-depth analysis of the latest trends persuading the business outlook. The report also offers a concise summary of statistics, market valuation, and profit forecast, along with elucidating paradigms of the evolving competitive environment and business strategies enforced by the behemoths of this industry.

The recent report about the Efavirenz/Tenofovir/Emtricitabine Combination Drug market is a detailed synopsis of the projections of this business space in tandem with an evaluation of the industry segmentation. The report depicts the Efavirenz/Tenofovir/Emtricitabine Combination Drug market to evolve as one of most profitable verticals, procuring substantial valuation by the end of the estimated duration, while simultaneously registering a profitable growth rate over the forecast timespan. The expansion opportunities that are prevalent in this business alongside the industrys geographical reach have also been stated in the report.

Request a sample Report of Efavirenz/Tenofovir/Emtricitabine Combination Drug Market at:https://www.marketstudyreport.com/request-a-sample/2055291?utm_source=intelligencejournal.com&utm_medium=sp

An inherent overview of this report:

Recognizing the basic business drivers and challenges:

Unveiling the geographical landscape of this market:

Ask for Discount on Efavirenz/Tenofovir/Emtricitabine Combination Drug Market Report at:https://www.marketstudyreport.com/check-for-discount/2055291?utm_source=intelligencejournal.com&utm_medium=sp

Describing the competitive spectrum of the Efavirenz/Tenofovir/Emtricitabine Combination Drug market:

A succinct outline of the Efavirenz/Tenofovir/Emtricitabine Combination Drug market segmentation

For More Details On this Report: https://www.marketstudyreport.com/reports/global-efavirenz-tenofovir-emtricitabine-combination-drug-market-growth-2019-2024

Some of the Major Highlights of TOC covers:

Development Trend of Analysis of Efavirenz/Tenofovir/Emtricitabine Combination Drug Market

Marketing Channel

Market Dynamics

Methodology/Research Approach

Related Reports:

1. Global Induced Pluripotent Stem Cells (iPSCs) Market Growth (Status and Outlook) 2019-2024Induced Pluripotent Stem Cells (iPSCs) market research report provides the newest industry data and industry future trends, allowing you to identify the products and end users driving Revenue growth and profitability. The industry report lists the leading competitors and provides the insights strategic industry Analysis of the key factors influencing the market.Read More: https://www.marketstudyreport.com/reports/global-induced-pluripotent-stem-cells-ipscs-market-growth-status-and-outlook-2019-2024

2. Global Veterinary Cephalosporin Market Growth 2019-2024Veterinary Cephalosporin Market Report covers a valuable source of perceptive information for business strategists. Veterinary Cephalosporin Industry provides the overview with growth analysis and historical & futuristic cost, revenue, demand and supply data (as applicable). The research analysts provide an elegant description of the value chain and its distributor analysis.Read More: https://www.marketstudyreport.com/reports/global-veterinary-cephalosporin-market-growth-2019-2024

Read More Reports On: https://www.marketwatch.com/press-release/at-285-cagr-solid-state-lidar-market-size-poised-to-touch-usd-7330-million-by-2025-2019-09-19

Contact Us:Corporate Sales,Market Study Report LLCPhone: 1-302-273-0910Toll Free: 1-866-764-2150 Email: [emailprotected]

Originally posted here:
Efavirenz/Tenofovir/Emtricitabine Combination Drug Market Overview with Detailed - News by Intelligence Journal

Can Consciousness be Created? – University Observer Online

Scientists have produced mini brains that mimic preterm babies brains, have they created consciousness too? Jade Norton investigates.

It is difficultfor us to comprehend our own consciousness, let alone try to operationallydefine it in a scientific experiment. In the last centuryscientificadvancement has allowed for experiments to be conducted that cross the fieldsof possibility and allow humans to play their hand at creation. However, thereare many ethical considerations that come along with this. For example, whatresponsibilities would suddenly arise if a tissue on a bench could not onlyreact to experimental procedures but had an opinion on them? On the other hand,what if the creation of consciousness in the pursuit of understanding can leadto answers that would not have been answered otherwise? This raises thequestion of whether scientists should aim to create consciousness or is itsomething that should be left to the natural world without human interference?

One recentexperiment undertaken by scientists from the University of California, SanDiego used stem cell technology to create cortical organoids or minibrains that are capable of producing brain signals that mimic that ofpremature babies. The brains do not look like a typical human brain and areinstead a smooth pea-sized blob that is encased in a nutrient-rich medium. Theylack the folding seen in a human brain as they do not contain grey and whitematter but are more of a mass of neural tissue. An induced pluripotent stemcell, which is a cell capable of dividing into any cell in the human body withthe right instructions, was used to create the brain cells. These cells dividedand over the course of 10 months grew from base neuronal cells toneuroepithelium-like structures which are similar to that of human braintissue. These organoids were not capableof complex thought but were created with the idea of using them to studyneurological diseases.

Throughout thedevelopment of the tissue nested oscillatory network dynamics were measured, theseare networks of repetitive electrical activity produced by the human brain inresponse to stimuli.This electrical activity can be found in all livingneurological tissue but does not necessarily show consciousness as there is yetto be an electrical ping signalling life as we currently understand it.

The team in SanDiego measured oscillatory spikes from the minibrains weekly usingmicroelectrode arrays and found an increase in activity as the monthsprogressed. This implied that there was a neural network capable of newdevelopment contained in the tissue. The electrical activity spawned by theneural network of the cortical organoids produced in the lab was recorded andsaved. Then using an EEG (electroencephalograph) the scientists measured the neuralactivity of a premature baby. These neural patterns were compared to see ifthere was a substantial difference between the neural activity between them.The comparison used a subset of features from the EEG to offset variablefactors not found in the cortical organoid. The results of comparison using amachine-learning algorithm found that the development of each tissue had manysimilarities which were likely to have been part of a genetically programmedtimeline. However, these minibrains were unable to progress to furtherdevelopment than that of a premature baby and it is thought that this is due tothe lack of sensory input that would usually be felt through the womb by apremature baby.

The minibrains that were developed in this experiment did not have any evidence ofconsciousness and were almost one million times smaller than a human brain andwithout the multiple types of cerebral cells they didnt have the capability ofdeveloping the full neurological complexity that is needed to form consciousnessas we see it. The measurements of electrical activity were done withoutcomparison of physiological features which varied greatly between the twotissues and have an effect on the maturation of neurons essential fordevelopment. The reality of creating a sentient being similar to ourselves isstill resting in the world of science-fiction, but the ability to create atissue that mimics brain activity and can be used in medical research is adefinite possibility. Brains can now be grown on a petri dish, but as of yetthey havent voiced any complaints.

The ability togrow an organoid that has an extensive neural network that is similar to thatof a preterm baby raises the question of at what point does consciousnessarise? It depends on who you ask. The origin of consciousness has yet to have auniversal consensus and without it there are no clear ethical rules relating tothe growth and development of cerebral tissue. There is no indicator that willtell you that consciousness has been created so it is possible that there is oronce was a homegrown sentient lab tissue somewhere.

Along with theadvancements in organoid technology, ethical considerations will continue tocome into question. Without the ability to know when consciousness has dawned,how do you know if the organoid is feeling pain or is distressed? And oncesomething develops a consciousness it becomes a subject of an experiment ratherthan an object which entitles it to its own rights. Consequently, this wouldseem that it would give scientists the responsibility to uphold these rights,however, this is still a largely unexplored area.

With theknowledge of ethical responsibility in hand, the possibilities of opportunityfor advancement is huge with a literal minibrain to work with. Medical researchcan use these organoids to see the in vivo effects of certain mental illnessessuch as schizophrenia and epilepsy and see the progression of neurodegenerativediseases such as Parkinsons and Alzheimers without the invasive problem ofviewing it in a live person. The question of when consciousness begins issomething that can fuel a philosophers career but for a scientist the creationof consciousness is a possibility that has never before been so accessible,with increasing advancements we may soon have our own brain in a jar.

See the original post here:
Can Consciousness be Created? - University Observer Online

Lineage Cell Therapeutics to Present at 2019 Cell & Gene Meeting on the Mesa on October 3, 2019 – BioSpace

Organized by the Alliance for Regenerative Medicine, the Cell & Gene Meeting on the Mesa is a premier conference combining discussions between senior executives and top decision-makers in the industry. The program also includes presentations by the fields most promising companies in the areas of cell therapy, gene therapy, gene editing, tissue engineering, and broader regenerative medicine technologies and extensive one-on-one partnering capabilities.

A live video webcast of all company presentations will be available at: http://www.meetingonthemesa.com/webcast and will also be published on the conference website shortly after the event.

About Lineage Cell Therapeutics, Inc.

Lineage Cell Therapeutics is a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs. Lineages programs are based on its proprietary cell-based therapy platform and associated development and manufacturing capabilities. With this platform Lineage develops and manufactures specialized, terminally-differentiated human cells from its pluripotent and progenitor cell starting materials. These differentiated cells are developed either to replace or support cells that are dysfunctional or absent due to degenerative disease or traumatic injury or administered as a means of helping the body mount an effective immune response to cancer. Lineages clinical assets include (i) OpRegen, a retinal pigment epithelium transplant therapy in Phase I/IIa development for the treatment of dry age-related macular degeneration, a leading cause of blindness in the developed world; (ii) OPC1, an oligodendrocyte progenitor cell therapy in Phase I/IIa development for the treatment of acute spinal cord injuries; and (iii) VAC2, an allogeneic cancer immunotherapy of antigen-presenting dendritic cells currently in Phase I development for the treatment of non-small cell lung cancer. Lineage is also evaluating potential partnership opportunities for Renevia, a facial aesthetics product that was recently granted a Conformit Europenne (CE) Mark. For more information, please visit http://www.lineagecell.com or follow the Company on Twitter @LineageCell.

View source version on businesswire.com: https://www.businesswire.com/news/home/20190923005243/en/

Read more here:
Lineage Cell Therapeutics to Present at 2019 Cell & Gene Meeting on the Mesa on October 3, 2019 - BioSpace

Certain Anatomical Sites Appear to Respond Well to an Investigational T-Cell Therapy for HPV-Positive Epithelial Cancers – Cancer Therapy Advisor

There have been promising results in a few patients with human papillomavirus (HPV)-positive epithelial cancers who were treated with innovative T-cell therapies, according to a study published in the Journal of Clinical Oncology.1

The idea behind the treatmentis to target a constitutively expressed tumor antigen expressed only in tumorcells and not healthy tissue, said Christian Hinrichs, MD, investigator in theexperimental transplantation and immunology branch at the National CancerInstitute, NIH Lasker Clinical Research Scholar, and lead author of theresearch.

T cells are taken from thepatient and genetically engineered to express a T-cell receptor (TCR) targetingan HPV viral oncoprotein expressed on HPV-associated cancers. They are thenexpanded to huge numbers (up to 100 billion cells) and infused back into thepatient.

The main toxicities arerelated to the chemotherapy given in the conditioning regimen cyclophosphamideand fludarabine, said Dr Hinrichs, noting that these toxicities included bonemarrow toxicity, bleeding, and an increased risk of infection.

Any significant clinicalbenefit of engineered T cells so far has generally been limited to their use inhematological cancers. Why has progress been so slow for other cancer types?

This approach is similar to [chimericantigen receptor] CAR T-cell approaches, but the difference is that we dontuse a CAR that can only target antigens on the surface of the cell. We use aTCR that can target intracellular antigens. Many of the most attractiveantigens in oncology such as KRAS and BRAF are intracellular, hence, cant betargeted with CARs, said Dr Hinrichs.

Two patients enrolled in the trialwere described as having an objective response to the therapy, with 1 patient,in particular, having a remarkable response.

The best response was in awoman with metastatic anal cancer where 1 of her lesions went away completelyand another 2 shrank completely. We then operated to remove the residualdisease; shes now 4 years out with no disease. She had metastatic cancer; itsremarkable and [she] has gone years with no cancer, said Dr Hinrichs.

Go here to read the rest:
Certain Anatomical Sites Appear to Respond Well to an Investigational T-Cell Therapy for HPV-Positive Epithelial Cancers - Cancer Therapy Advisor

Dual-Targeted CAR-T Therapies in Solid Tumors: Q&A With Dr Wayne Marasco – Cancer Therapy Advisor

The dawn of chimeric antigen receptor (CAR) T-cell (CAR-T) therapies ushered in a period of intense medical innovation. Despite this, researchers are still struggling with translating the success seen with CAR-T in hematologic malignancies into the area of solid tumors.

Wayne Marasco, MD, PhD, professor in the department of cancer immunology at Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, is investigating the use of CAR-T in triple negative breast cancer (TNBC) and ovarian cancer. His lab, in collaboration with the Dana-Farber Cancer Institute, entered into an exclusive option with OncoSec for the company to license the product candidates and the associated intellectual property resulting from the research coming out of the Marasco lab using engineered single-chain variable fragment (scFv) antibodies in a dual-targeted bispecific CAR T-cell approach.1

His interests include marrying stimulatory cytokines and anti-inhibitory antibodies to break through the hostile tumor microenvironment that exists in solid tumors. To do this, he envisions using the local delivery of CAR-T cells to restore local antitumor immunity in the tumor microenvironment, and then allowing educated T cells to get out of the tumor cells so they can contribute to a systemic immune surveillance system that may help cells throughout the body persist against cancer for the long term.

Cancer Therapy Advisor sat down to speak to Dr Marasco to find out if he thinks CAR-T therapies should be categorized as cell or gene therapies, the feasibility of the approaches that can be used to deliver CAR-T payloads, and how dual-targeting CAR-Ts could be the one of the most durable options across adoptive cell therapy approaches.

This interview has been lightly condensed and edited for the purpose of clarity.

Cancer Therapy Advisor (CTA): Im curious about the use of a vaccine boost with CAR-T theres new research thats been out with other teams that combines the 2, and I was wondering how that works and if you could explain it.

Dr Marasco: So, first of all, I havent made it through the Ma et al. paper2 in great detail Lets just talk about the big picture, and that is that CAR-T cells can deliver payloads.

What may not be evident from what youve read from the press releases,1 and the internal information, is that we have designed CAR-T cell factories. So, theyre not just CAR-T cells, the whole basis of the work that we do is deliver payloads. So, the CAR-T cells not only get to the tumor in an antigen-specific way and thats where the dual targeting comes in once they get there, they secrete molecules locally, at the tumor site, to change the tumor microenvironment.

In the case of the vaccine boost, its really that concept that youre allowing molecules get to antigen-presenting cells to be able to boost the local immunity there. So, I havent been able to get through the paper in detail yet, but thats, basically, the 64,000-foot view of what theyre trying to do.

So, the idea of using CAR-T cells to deliver payloads, and to change the tumor microenvironment is inherent in the approach that is now published in this vaccine paper, as well as the work that we do, which is to change the tumor microenvironment in a different way the end result being restoration of immunities so that educated T cells that get to the tumor, that cant do anything because they are suppressed, become unsuppressed, if you will, and restore local antitumor immunity.

CTA: Based on the press release that I read [about the partnership with OncoSec, The Marasco Laboratory, and the Dana-Farber Cancer Institute], some candidates were mentioned in that release. Could you share which ones they are?

Dr Marasco: Were not releasing the targets yet because the work is still fairly early on, and we dont want to disclose what the actual targets that were doing are. The diseases that were looking at, I think, are fair game, and to that question, thats triple-negative breast cancer, as well as ovarian cancer, which was not mentioned in the press release, but thats the other cancer that were working on for the team so, 2 womens cancers.

CTA: There was a mention of the [use of OncoSecs] intratumoral TAVO IL-12, that would help facilitate getting the actual engineered CAR-T cells into the tumor microenvironment. How does that work, and also, how does that keep them persistent in that microenvironment?

Dr Marasco: So, the data (OncoSecs and the science that led to it) really show that IL-12 is a pretty potent cytokine to enhance T-cell stimulation, and I think the fact that theyre getting the clinical responses that they are shows that its working when injected locally perhaps systemically, but certainly locally. So, the idea there is that that, in and of itself, is changing the tumor microenvironment.

The limitations of it, of course, are that its a plasma-based therapy, so that when you do your local electroporation, youre getting the IL-12 gene taken up by the cells that are being electroporated, secreting that locally, thats enhancing the entire local immune system, including recruitment of white blood cells. And to an extent thats not totally worked out, because we just dont have enough data yet to carve it in stone, is that theyre also changing the tumor microenvironment. So, the concept here is that whatever boost that we can get in the tumor microenvironment to be able to let those CAR-T cells work more potently, would be an added benefit.

So, for example, in our case, the work that weve published so far has looked at the PD-1/PD-L1 axis by secluding antiPDL-1 locally at the tumor site. So, we know from many clinical trials now that that is certainly 1 of the keystones in the tumor microenvironment, that particular axis, but it doesnt work 100% in patients, and it varies depending on the tumor, and a number of other factors. So, PD-L1/PD-1, and CTLA-4 are 2 of the cornerstones in that they, in themselves, may not be enough.

So, those 2 axes that have led to the whole breakthrough in the field, are really to put on the brakes of suppressive molecules. Theyre not costimulatory; theyre blocking inhibitory pathways. So, when you look at the tumor microenvironment, and the whole way T cells get stimulated, theres a number of molecules that suppress T-cell stimulation, and theres a number of molecules that stimulate it. So, with therapy support, you only gain reverse in suppression. So, the idea of IL-12 is that it would be stimulatory.

If you combined a stimulatory cytokine, with the correct T cell thats secreting anti-inhibitory antibodies, you may be able to get marked change in the tumor microenvironment, and therefore lead to a significant increase in T-cell simulation. So, thats the idea between marrying the 2 therapies.

Read more:
Dual-Targeted CAR-T Therapies in Solid Tumors: Q&A With Dr Wayne Marasco - Cancer Therapy Advisor

Healthy bone marrow may be important in fertility – BioNews

23 September 2019

A study in mice suggests that bone marrow-derived stem cells may play a role in establishing pregnancy.

The research showed that the stem cells can travel through blood circulation to the uterus, making it more receptive for a new embryo. Specifically, the authors showed that these cells concentrate in the lining of the uterus where the embryo is about to implant. There, they become specialised uterine cells or decidual cells, which are critical for maintaining the embryo.

'We have always known that two kind of things were necessary for pregnancy: you must have ovaries to make eggs, and you must also have a uterus to receive the embryo,' said senior author, Dr Hugh Taylor at Yale University in New Haven, Connecticut. 'But knowing that bone marrow has a significant role is a paradigm shift.'

Previous studies had shown that small numbers of bone-marrow stem cells contribute to the renewal of the lining of the non-pregnant uterus, but it remained unknown whether they play a part in pregnancy.

This study is the first to show a physiological role for bone-marrow stem cells in pregnancy.

This work was possible due to a methodological breakthrough. Dr Taylor and his team at Yale were able to develop a mild chemotherapy for their mouse model that 'wiped out' the bone marrow of these mice without affecting their eggs, and therefore their fertility. Then they fertilised these mice before and after healthy bone-marrow transplantation to investigate whether the bone-marrow stem cells contributed to the establishment of pregnancy.

The team also used mice that lack a protein called Hoxa11, usually expressed in both uterine and bone marrow progenitor cells - mice without this protein have a deficient womb and cannot become pregnant. Mice that only partially lack Hoxa11 can become pregnant, but they experience recurrent miscarriages. When these mice received bone marrow transplants from healthy mice, both sets were able to become pregnant. The partially-deficient mice went ahead to have as many pregnancies as their healthy mice.

Several studies have implicated Hoxa11 production and conditions that relate in pregnancy failure, such as endometriosis. The authors suggest further investigations for the role of Hoxa11 and bone-marrow stem cells in the human pregnancy and its establishment.

'We are currently translating these findings into humans to better understand the role that these bone marrow-derived stem cells play in recurrent implantation failure and recurrent pregnancy loss, two conditions that are unexplained in the majority of women and have no effective treatment,' said Dr Reshef Tal, study first author.

'The findings of this study open exciting new avenues for research into the cause of these conditions as well as developing new treatments for women suffering from them.'

The research was published in PLOS Biology.

Go here to see the original:
Healthy bone marrow may be important in fertility - BioNews

Actinium Announces Iomab-B Poster Selected for Honorable Distinction Award at the 2019 Society of Hematologic Oncology Annual Meeting from Nearly Four…

NEW YORK, Sept. 23, 2019 /PRNewswire/ --Actinium Pharmaceuticals, Inc., (NYSE AMERICAN: ATNM) ("Actinium") today announced that a poster highlighting Iomab-B, its pivotal Phase 3 targeted conditioning candidate, was awarded Honorable Distinction at the 2019 SOHO (Society of Hematologic Oncology) Annual Meeting. SOHO is the only international society specific to the field of hematologic oncology and has grown to over 3,000 members. This year's SOHO annual meeting was attended by nearly 1,400 physicians, nurses and healthcare professionals and nearly four hundred abstracts and posters were presented including over 70 focused on AML or acute myeloid leukemia.

Benjamin Tomlinson, M.D., Assistant Professor, Adult Hematologic and Stem Cell Transplant Section, Seidman Cancer Center, University Hospitals Case Medical Center (Cleveland, OH) and lead author of the poster, said, "It is an honor for our work to be recognized by SOHO's scientific committee from the significant number of posters and abstracts that were submitted. The AML therapeutic landscape has evolved rapidly in recent years with eight therapies gaining approval since 2017 including targeted agents like Bcl-2, FLT3 and IDH inhibitors. While these therapies are important advancements for patients with AML, they are not curative, and bone marrow transplant remains the only curative treatment option for patients with active relapsed or refractory AML. Iomab-B is highly differentiated as a targeted agent with a strong anti-leukemic effect as we have demonstrated in this poster selected by SOHO and targeted conditioning ability that led to all patients receiving Iomab-B achieving successful bone marrow transplant and engraftment. These findings are highly encouraging as I am not aware of any other agents that offer such a high probability of bone marrow transplant for this patient population. I look forward to continuing to participate in the SIERRA study and am excited for additional data in the future."

Mark Berger, M.D., Actinium's Chief Medical Officer, said, "This Honorable Distinction award from SOHO adds to the growing recognition for Iomab-B's value proposition as the only late-stage targeted conditioning agent for the older relapsed or refractory AML patient population. Since achieving twenty-five percent enrollment and making important changes to the trial protocol, including adding targeted therapies like venetoclax as options in the control arm and reducing the time to crossover evaluation to fourteen days, we have seen a dramatic increase in physician interest and enthusiasm for the SIERRA trial. This groundswell of interest continued to build after preliminary data from the first twenty-five percent of patients was presented in an oral presentation at the ASH annual meeting in 2018 and a late-breaking oral presentation at the TCT annual meeting in February 2019. These data demonstrated Iomab-B's ability to enable transplant universally, with deep donor chimerism and no non-relapse mortality at one hundred days post-transplant in the Iomab-B arm. Additionally, Iomab-B's ability as a single agent to rapidly deplete all circulating leukemic blasts prior to transplant has drawn strong recognition from the medical community, as evidenced by this award from SOHO. These data gained widespread visibility throughout the transplant and hematology communities and as a result, we have seen new sites come into the SIERRA trial bringing us to twenty sites in total at present. There has also been significant physician engagement, which drove us powerfully past fifty-percent enrollment. With the important fifty percent enrollment milestone achieved, we look forward to completing the SIERRA study and further demonstrating Iomab-B's value proposition at future medical meetings."

The poster presented at SOHO highlighted Iomab-B's ability as a single agent activity to rapidly deplete peripheral blasts leading to lower circulating leukemia tumor burden prior to BMT, which is critical for successful engraftment. It was observed that a single therapeutic infusion of Iomab-B resulted in a median reduction of peripheral blasts of 98% by day 3 and 100% reduction by day 8 following administration and prior to any other pre-BMT conditioning in the sixteen patients who were evaluated. Rapid reduction of peripheral blasts has been observed as an independent prognostic marker that is predictive of both CR or Complete Response and RFS or Relapse-Free Survival in patients with AML after receiving cytotoxic chemotherapy. Gianfaldoni et al1 performed an analysis of 30 newly diagnosed AML patients who were treated with cytotoxic induction chemotherapy and found that a rapid reduction of peripheral leukemia blasts correlated with responses and all patients that achieved CR had a rapid reduction of their peripheral blasts. Elliot et al2, performed a retrospective analysis of 86 adult patients with AML and identified time to clearance of circulating leukemia blasts as an independent prognostic marker of RFS that superseded all other known risk factors including karyotype and number of cycles of induction therapy needed to achieve CR. As previously presented, all patients receiving Iomab-B in the SIERRA trial, including cross over patients, received a BMT and achieved engraftment without delay.

The poster selected by SOHO for honorable distinction can be viewed on Actinium's website (here) or the SOHO Annual Meeting website (here).

About the Society of Hematologic OncologyThe Society of Hematologic Oncology (SOHO) is an international society designed specifically for clinicians, research scientists and related healthcare professionals who specialize in the research and treatment of patients with hematologic malignancies. SOHO's mission is to promote worldwide research and education through the exchange of scientific information. Organized by its founders and world class committees, SOHO is the only international society specific to this field. The 2019 SOHO Annual Meeting took place September 11-14 in Houston, Texas, with attendance from nearly 1,400 hematologic oncology professionals from across the globe. Nearly 400 abstracts were accepted for oral or poster presentation at the Annual Meeting. Published abstracts are available through the official journal of the Society, 'Clinical Lymphoma, Myeloma and Leukemia,' published by Elsevier. Online access is open to the public at https://www.clinical-lymphoma-myeloma-leukemia.com/issue/S2152-2650(19)X0009-9through December 31, 2019. For more information about the Society or to sign-up for FREE membership, go to the official website at https://www.sohoonline.org/.

About Iomab-B Iomab-B is an ARC or Antibody Radiation-Conjugate comprised of the anti-CD45 antibody apamistamab and the radioisotope iodine-131 that is intended to be a targeted conditioning agent prior to a BMT or bone marrow transplant. Iomab-B was developed at the Fred Hutchinson Cancer Research Center and has been studied in over 300 patients in multiple hematologic indications across 12 clinical trials in addition to the ongoing SIERRA study in older patients with active, relapsed or refractory AML or Acute Myeloid Leukemia prior to patients receiving an allogeneic BMT or bone marrow transplant. Iomab-B is Actinium's lead targeting conditioning ARC in its multi-target, multi-indication targeted conditioning pipeline that includes the Iomab-B and Actimab-MDS programs for BMT and the Iomab-ACT program that will study a lower dose of Iomab-B for lymphodepletion prior to CAR-T and other cellular therapies.

About Actinium Pharmaceuticals, Inc.Actinium Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on improving patient access and outcomes to cellular therapies such as BMT or Bone Marrow Transplant and CAR-T with its proprietary ARC or Antibody Radiation-Conjugate targeted conditioning technology. Actinium is also developing its proprietary AWE or Antibody Warhead Enabling technology platform, which utilizes radioisotopes including iodine-131 and the highly differentiated actinium-225 coupled with antibodies, to target a variety of antigens that are expressed in hematological and solid tumor indications. It is developing a multi-disease, multi-target pipeline of clinical-stage ARC's targeting the antigens CD45 and CD33 for targeting conditioning and as a therapeutic either in combination with other therapeutic modalities or as a single agent for patients with a broad range of hematologic malignancies including Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS) and Multiple Myeloma (MM). Actinium's lead product candidate, Iomab-B, is in a pivotal Phase 3 trial for re-induction and conditioning prior to a BMT for patients with active relapsed or refractory AML or Acute Myeloid Leukemia. BMT is the only curative treatment option for this patient population and currently no standard of care exists. Actimab-MDS is its second pivotal program for targeted conditioning that will study the ARC comprised of the anti-CD33 monoclonal antibody lintuzumab linked to the radioisotope actinium-225 in patients with high-risk MDS in combination with RIC or Reduced Intensity Conditioning prior to a BMT. Its Iomab-ACT or Adoptive Cell Therapy program targets CD45 and utilizes a lower dose of iodine-131 than Iomab-B or lutetium-177 and is intended to be used for targeted conditioning or lymphodepletion prior to CAR-T and adoptive cell therapies as a replacement to non-optimized chemotherapies, such a Flu/Cy or fludarabine and cyclophosphamide, that is used in standard practice today. Actinium also has multiple clinical trials ongoing, in startup phase, or in planning, to use its CD33 ARC in combination with other therapeutic modalities such as chemotherapy, targeted agents or immunotherapy. It has initiated several combination trials, including a doublet combination trial with its CD33 ARC and venetoclax, a BCL-2 inhibitor, for patients with relapsed or refractory AML, a triplet combination trial with venetoclax and an HMA or hypomethylating agent and in combination with the salvage chemotherapy regimen CLAG-M (cladribine, cytarabine, filgrastim and mitoxantrone) for patients with relapsed or refractory AML. Actinium is also studying its CD33 ARC as single agent for patients with penta-refractory multiple myeloma. Its AWE technology platform enables Actinium's internal pipeline and with the radioisotope actinium-225 is being utilized in a collaborative research partnership with Astellas Pharma, Inc. Actinium's clinical programs and AWE technology platform are covered by a portfolio of over 100 patents covering composition of matter, formulations, methods of use, the DOTA linker technology for actinium-225 applications and methods of manufacturing the actinium-225 radioisotope in a cyclotron.

Sources:

1) Gianfaldoni et al. clearance of leukemic blasts from peripheral blood during standard induction treatment predicts the bone marrow response in acute myeloid leukemia: a pilot study. British Journal of Haematology, 2006 March 16; 134, 54-57.

2) Elliott et al. Early peripheral blood blast clearance during induction chemotherapy for acute myeloid leukemia predicts superior relapse-free survival. Blood. 2007 Dec 15; 110(13):4172-4. Epub 2007 Oct 1.

Forward-Looking Statements for Actinium Pharmaceuticals, Inc. This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time.

Contact:

Actinium Pharmaceuticals, Inc. Actinium Pharmaceuticals, Inc.Steve O'LoughlinPrincipal Financial Officerinvestorrelations@actiniumpharma.com

Hans VitzthumLifeSci Advisors, LLCHans@LifeSciAdvisors.com(617) 535-7743

View original content to download multimedia:http://www.prnewswire.com/news-releases/actinium-announces-iomab-b-poster-selected-for-honorable-distinction-award-at-the-2019-society-of-hematologic-oncology-annual-meeting-from-nearly-four-hundred-abstracts-300923027.html

SOURCE Actinium Pharmaceuticals, Inc.

Here is the original post:
Actinium Announces Iomab-B Poster Selected for Honorable Distinction Award at the 2019 Society of Hematologic Oncology Annual Meeting from Nearly Four...