Cell Biology

Synthetic Biology Market is Projected to Expand at a CAGR of 26.3% from 2019 to 2027 – 3rd Watch News

Synthetic Biology Market: Introduction

Transparency Market Research has published a new report titled, Synthetic Biology Market. According to the report, the globalsynthetic biology marketwas valued atUS$ 4.96 Bnin2018and is projected to expand at a CAGR of26.3%from2019to2027.

In terms of product, the core product segment accounted for major share of the global synthetic biology market in2018. The segment is anticipated to witness strong growth from2019to2027. The core product segment is further sub-segmented into synthetic DNA, synthetic genes, synthetic cells, XNA (xeno nucleic acid), and chassis organisms. The synthetic DNA sub-segment accounted for major share of the global synthetic biology market due to the increasing research & developmental activities associated to this sub-segment and increased penetration in the market.

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Based on technology, the genome engineering segment held a major share in2018in synthetic biology market, due to its ability to make alterations to the genome of the living cell, and thereby gaining attention of the scientists and key players.

Based on application, the health care segment held a prominent share in2018in synthetic biology market due to increase in prevalence of various diseases, rise in key players, and expanding infrastructure as well as increasing focus of government in treatments and facilities in health care

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Global Synthetic biology Market: Prominent Regions

North America held the largest share of the global synthetic biology market in 2018. North America accounted for significant share of the global synthetic biology market in2018.The market in the region is likely to grow at a rapid pace during the forecast period.

The U.S. is projected to dominate the synthetic biology market in the region during the forecast period, owing to early adoption of technologies. The country is anticipated to be the most attractive market for synthetic biology, with high attractiveness index.

Global Synthetic Biology Market: Key Players

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Synthetic Biology Market is Projected to Expand at a CAGR of 26.3% from 2019 to 2027 - 3rd Watch News

Cell Biology

All About the Berkeley Lights Stock IPO – Nanalyze

For some reason, IPOs are coming out of the woodwork these days. Seems strange when you consider that just three months ago, all hell was breaking loose, and everyone seems to have forgotten about that. In fact, since the first-ever mention of the Woohoo Flu, the Nasdaq has gone up by +13%. Maybe everyones rushing to IPO before the door slams shut again?

It was only several months ago that we wrote about How Berkeley Lights Enables Synthetic Biology, and now theyve filed for an IPO, which means we get to take a look under the hood. Well assume youre already familiar with the company from our previous piece and jump right into their S-1 filing to look for juicy insights.

The value proposition on offer from Berkeley Lights is that researchers can do a lot more, with a lot less, and do it much quicker. An entire roomful of equipment can be replaced with a single platform called The Beacon Optofluidic System where wells are replaced with chips. (Remember organs-on-a-chip? Well this is lab-on-a-chip.) The core technology behind the Beacon platform are OptoSelectchipsthat contain thousands of NanoPen chambers which are like wells on a microplate.

The chips you see above are capable of not only sorting cells, but measuring their characteristics. All of this takes place rapidly, at scale. The platform is operated through an easy-to-use software interface which guides the entire laboratory workflow which thanks to automation can operate at lightening speeds. For example, discovering an antibody is a process that would typically take about three months. Using the Beacon platform, that same process takes just a single day.

Cells are microscopic factories that make minute amounts of a variety of valuable proteins, such as antibodies, and therefore require a high degree of precision when analyzed individually, Berkeley Lights correctly points out. Now, just imagine taking thousands of cells and measuring the individual characteristics of each cell to only select a chosen few. These capabilities can be configured as customized workflows which are unique to a customers particular requirements, something that translates into a total addressable market of approximately $23billion:

It all works out to about 1,600companies, academic institutions, and governmental and other organizations which Berkeley can sell their Beacon platform to using three different revenue models:

The company also talks about the Berkeley Lights BioFoundry which may develop proprietary valuable biological assets they could sell or license to customers, such as functionally validated antibodies or new organisms applicable to synthetic biology.

Since the first commercial sale of Beacon in the United States in December 2016, Berkeley Lights has just dipped their toes in the water with 45 customers and an install base of 54 Beacon machines. The customer list includes eight of the ten largest biopharmaceutical companies in the world who comprised 18% of their total revenues in 2019 which came in at $56.7 million, a growth of +81% over 2018 revenues of $31.3 million.

About 70% of their 2019 revenues came from direct sales while the other 30% came from strategic partnerships like the one with Ginkgo Bioworks we discussed in our previous article. A breakdown of revenues by addressable markets shows that most the money in 2019 came from the antibody therapeutics segment:

We also see heavy spending on R&D at around $38 million in 2019, a number thats equivalent to 67% of revenues at the moment (nearly 42% of all 210 employees work in R&D). That spending is to ensure their intellectual property moat is strong and to stay well ahead of any competitors, or in the case of Berkeley Lights, potential competitors.

One valuable piece of information presented in the S-1 filing is a list of names that Berkeley Lights describes as potential competitors. The use of the word potential implies that the Beacon platform is so advanced that their nearest competitors can only accomplish parts of what they do. Being able to discover an antibody in a single day vs. three months is an exponential leap forward, and represents an entirely new way of doing things, as opposed to incremental improvements over existing methods. Lets quickly look at the names Berkeley Lights listed as potential competitors.

Maybe were overthinking Berkeley Lights use of the term potential competitors, but were inclined to think that at least some of that lab equipment being replaced by a single Beacon platform comes from the first three companies listed above that all seem to be more mature, with each claiming high levels of industry adoption. The fourth company is a relatively new startup that seems to be making similar claims as Berkeley Lights regarding their ability to sort cells at scale:

Investors must love how the core technology developed by Berkeley Lights, the OptoSelect chips, also happen to be consumables. In some business models, companies will simply give away a platform because high-margin consumables will more than pay for it over a short period of time. Investors will want to watch how the new subscription service evolves, and use number of customers and machines deployed as key metrics.

In the companys words, a key factor to our future success will be, our ability to increase the adoption of our platform. They have eight of the largest biopharma companies as reference clients. Now, their 37 salespeople need to go out and get these machines in the hands of the remaining 1,555 possible customers theyve identified.

If the IPO proceeds as planned, shares of Berkeley Lights will trade under the ticker BLI.

Here at Nanalyze, we hold the lion's share of our investing dollars in a portfolio of 30 dividend growth stocks. Find out which ones in the Quantigence Dividend Growth Investing report freely available to Nanalyze Premium subscribers.

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All About the Berkeley Lights Stock IPO - Nanalyze

Cell Biology

Researchers successfully use CAR-T therapy in blood cancer patients – News-Medical.Net

A method known as CAR-T therapy has been used successfully in patients with blood cancers such as lymphoma and leukemia.

It modifies a patient's own T-cells by adding a piece of an antibody that recognizes unique features on the surface of cancer cells.

In a new study, researchers report that they have dramatically broadened the potential targets of this approach - their engineered T-cells attack a variety of solid-tumor cancer cells from humans and mice.

They report their findings in the Proceedings of the National Academy of Sciences.

"Cancer cells express on their surface certain proteins that arise because of different kinds of mutations," said Preeti Sharma, a postdoctoral researcher at the University of Illinois at Urbana-Champaign who led the research with biochemistry professor David Kranz.

Kranz is a member of the Cancer Center at Illinois and an affiliate of the Carl R. Woese Institute for Genomic Biology, also at the U. of I. "In this work, we were looking at protein targets that have short sugar chains attached to them."

The abnormally short sugar chains on some types of cancer cells result from mutations that disrupt the molecular pathway that attaches these sugars to proteins, Sharma said. Drugs that bind to the aberrant sugars preferentially recognize cancer cells and spare healthy cells.

CAR-T therapy is a promising treatment for patients with certain types of blood cancers. But identifying binding sites in solid tumors has been more difficult, Kranz said.

"A major challenge in the field has been to identify targets that exist on cancer cells in solid tumors that are not present on normal tissue," he said.

The team started with a piece of an antibody that could serve as a receptor. The antibody was known to interact with a specific type of abnormally formed sugar attached to a protein on solid-tumor cancer cells in mice.

We realized that because this receptor binds both to the protein and the sugar on the surface of the cancer cell, there might be room to change the antibody so that it can bind to more than one protein attached to the short sugar. This could make it broadly reactive to different kinds of cancers."

Preeti Sharma, Postdoctoral Researcher, University of Illinois at Urbana-Champaign

Study co-author Qi Cai, another postdoctoral researcher in the Kranz lab, tested whether changes in the sequence of amino acids in the vicinity of the abnormal sugar affected the receptor's binding to the site. This allowed the team to determine if the antibody could be slightly changed to accommodate other sugar-linked cancer targets.

They conducted a series of mutation experiments focused on the essential parts of the antibody, Sharma said.

"We generated almost 10 million mutant versions of our receptor, and then we screened those to find the property we wanted," she said. "In this case, we wanted to broaden the specificity of that antibody so that it reacts not only to the mouse target but also to human targets."

Once they found the antibodies with the desirable traits, the researchers engineered them into T-cells and tested them with mouse and human cancer cell lines.

"Our engineered T-cells are showing activity against both human and mouse cancer cell lines," Sharma said. "And the T-cells can now recognize several different proteins that have short sugars attached to them.

This is really important because in cancer therapy, most of the time you are going after a single target on a cancer cell. Having multiple targets makes it very difficult for the cancer to evade the treatment."

"Although these engineered cells are early in development, we are particularly excited that we can use the same T-cell product to study efficacy and safety against cancers in mice and humans," Kranz said.

Source:

Journal reference:

Sharma, P., et al. (2020) Structure-guided engineering of the affinity and specificity of CARs against Tn-glycopeptides. Proceedings of the National Academy of Sciences. doi.org/10.1073/pnas.1920662117.

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Researchers successfully use CAR-T therapy in blood cancer patients - News-Medical.Net

Cell Biology

Versatile Vaccinex Needs A Trial Or Partner Win, But Scaled Down Operation May Be More Likely – Seeking Alpha

Investment Thesis

Vaccinex share price performance since IPO. Source: TradingView.

A review of Vaccinex's (VCNX) recent share price performance and funding runway might persuade investors to leave this early stage biotech stock well alone, but there is also a case to be made that the stock represents a risky potential buying opportunity ahead of some make-or-break trial results.

Vaccinex's lead candidate, Pepinemab - an inhibitor of semaphorin 4D ("SEMA4D") is a unique and potentially effective treatment not only for neurodegenerative diseases, but also for oncological indications.

So far, the treatment has failed to wow investors. A disappointing IPO that raised $39.6m - at the lower end of the company's $12 to $15 price range - generated little follow-on enthusiasm and the company's stock quickly fell to just $3.7.

Vaccinex's news-flow - from presenting data related to its SEMA4D antibody platform, ActivMAb antibody discovery platform, and Natural Killer T-cell vaccine platform, to updates from its 2 major clinical trials - for Huntington's disease and non-small cell lung cancer ("NSCLC") - has succeeded in lifting the share price to highs of $8 in May '19, $7 in September '19 and $7 in January this year. Trading volumes on each occasion were thin, however, and gains short-lived. As such, the company has struggled to raise cash and faces a mounting funding crisis.

On the flip side, major potential price catalysts lie ahead for the company. Full results from its phase 2 Huntington's SIGNAL study of Pepinemab are due to be announced in October, and the trial has already returned some positive results, with patients showing improvement in brain metabolism, halted brain atrophy and an easing of motor and cognitive symptoms after 6 months of treatment vs. placebo.

Meanwhile data from a phase 1/2b study of Pepinemab and Merck KGaA / Pfizer's (NYSE:PFE) Bavencio for NSCLC showed that 81% of patients treated experienced either a partial response or stable disease response, but it appears the company has not persuaded Merck KGaA to partner on a registrational trial that would progress the indication towards approval and commercialization.

Vaccinex's management say that they are considering trials for other oncological indications, provided they can find a suitable partner. The company expects to receive funding from the Alzheimer's Association and the Alzheimer's Drug Discovery Foundation to begin a study of Pepinemab in Alzheimer's patients, but enrollment has been delayed by COVID-19.

The company urgently requires fresh funding, or a partner, without which it will be forced to significantly scale down operations. There are several scenarios that I believe could play out for the company. One is that the stock remains stable until October, and when the full data from SIGNAL is released, rises on positive results, allowing the company to raise funding and proceed with a pivotal trial (it has already both Orphan Drug and fast-track designation from the FDA). Another is that the company is able to find a partner to further its oncological trials, which again is likely to lift the share price. A third is that the company uses its limited funding from Alzheimer's agencies to progress a trial for that indication. Failure to progress on any of these fronts would likely result in an eventual delisting from the NASDAQ.

In the rest of this article I will provide more detail on the company and try to determine the most likely outcome for this Rochester, New York based microcap. I suspect that October won't deliver the major price catalyst the company is looking for, due to insufficient efficacy, but longer term, its work could attract the backers it needs to support share price gains.

Vaccinex has been in existence since 2001 having been founded by President and CEO Maurice Zauderer, an academic who was an Associate Professor at the University of Rochester, senior faculty member at Columbia University and visiting scientist at National Cancer institute, Ontario Cancer Institute and Laboratory of Cell Biology. The rest of the management team and board combines a blend of academic and investment backgrounds, with some biotech experience, including at Biogen (BIIB) and Surface Oncology (NASDAQ:SURF).

The company has developed 3 platform technologies - its SEMA4D antibody platform and ActivMab discovery platform - marketed on the company website as an outsource-able mammalian cell based antibody discovery platform with unique multi-pass membrane target capabilities - and a Natural Killer T vaccine discovery platform.

As mentioned, the company's lead candidate is Pepinemab, a monoclonal antibody targeting SEMA4D. Within the neurology setting, SEMA4D controls activity of certain cells - most notably astrocytes and microglia, the innate inflammatory cells of the brain, whose activation is thought to contribute to neurodegenerative processes.

Pepinemab (VX15) blocks activities of SEMA4D. Source: company website.

Astrocytes and microglia are involved in the down-regulation of both glutamate receptors and glucose transporters but in their inflammatory state - which can be triggered by up-regulation of SEMA4D - the cells are unable to perform their normal functions and instead initiate secretion of inflammatory cytokines leading to the breakdown of neural networks and, Vaccinex believes the onset of diseases such as Huntington's, Alzheimer's, MS and ALS.

In the oncological setting, SEMA4D is also expressed by many types of tumor cells and may be correlated with tumor aggression and the blocking of immune cell infiltration and activity in tumors.

Vaccinex current pipeline. Source: company website.

Besides the Huntington's, Alzheimer's and NSCLC trials, Vaccinex has studies ongoing for Pepinemab with third party investigators in osteosarcoma and melanoma and certain other "window of opportunity" studies for other indications. There are 2 other candidates in limited development. VX5 - a human antibody to CXCL13, a molecule that regulates the formation of immune tissues - and VX25 - an investigational, bi-specific molecule, involved in the activation and targeting of NKT cell stimulation for cancer immunotherapy.

Prior to its IPO, Vaccinex obtained funding (according to the company's 2109 10K submission) by entering into numerous financing arrangements with Canadian Investment groups, including FCMI Financial. These complex arrangements culminated in a licensing agreement with a group of investors - including FCMI - known as VX3 - who agreed to various milestone payments up to a value of $32m in exchange for the rights to market and sell Pepinemab in the US and Canada.

Post IPO, the company has raised (that I can find, on top its initial $39.6m) amounts of $13.8m and $7.5m and has agreements in place with brokerages Jefferies and Keystone to sell up to $11.5m and $5.0m of shares, respectively, and has also received a small $1.1m loan via the CARES act. At the end of 2019 the company reported an accumulated deficit of $248.6m.

On one hand, investors could take the view that Vaccinex has burnt through a considerable amount of cash without having much to show for it. On the other, Vaccinex has now treated >300 patients across the 2 cohorts of its Huntington's trial and seems to have uncovered some promising, if inconclusive results, and treated 62 patients in its NSCLC trials, again delivering results that appear to be borderline sufficient to warrant further trial progression.

Although securing a high-profile partner such as Merck KGaA (known as EMD Serono in the US owing to sharing its name with Merck & Co.), and its drug - the PD-L1 inhibitor co-developed with Pfizer - Bavencio, could be seen as a coup for Vaccinex, in truth, the company still had to fund the investigational new drug application ("IND"), for this study, and shared trial costs, which may not have been such a wise move.

In 2019, trial costs accounted for $18.8m of the company's total R&D expenses. Although the company does not break down the individual costs of the Huntington's vs. NSCLC trials, we can assume a reasonable chunk of this was spent on NSCLC.

Merck KGaA and Pfizer's Bavencio was designed to compete with the likes of US Merck's (MRK) PD-1 inhibitor and mega-blockbuster Keytruda, and Bristol Myers Squibb's (BMY) Opdivo, but to date it has been a disappointment, struggling to secure approvals, and failing to meaningfully outperform its rivals across any indication - the drug pulled in sales of just $114m for Merck KGaA in 2019 whilst Opdivo and Keytruda are multi-billion sellers.

Being a huge market, NSCLC treatment is hugely competitive, and therefore I suspect it would have taken a small miracle for Pepinemab / Bavencio to return the kinds of results required to pursue an approval from the FDA. Instead, although I am not an expert of judging clinical trials, the results do not appear to have demonstrated sufficient promise or efficacy, have not impressed the market, and the experiment now appears to have been all but abandoned.

Having said that, whilst Vaccinex seems to have drawn a line under Pepinemab for NSCLC for now, it is possible that the trial has at least increased the value of Pepinemab as an asset, and perhaps there is a biotech or pharma out there that would consider an acquisition of Vaccinex, or an offer for its lead candidate, should the company's financial woes worsen, and it reach the point of no return.

In a recent Virtual Investor Fireside Chat, Vaccinex CEO Maurice Zauderer spent the majority of the call discussing the progress made in the Huntington's SIGNAL trial, which builds on preclinical studies in an animal model of Huntington's and safety data from a Phase 1 dose-escalation clinical trial of Pepinemab in MS patients that was completed in November 2014.

Data from Cohort A of the trial - which enrolled 36 patients - showed in April 2017 that treatment with Pepinemab induced a sharp increase in glucose metabolism in the brain as detected by FDG-PET imaging, which informed the design of the B Cohort of the trial, which has returned some results of note. After 6 months, Pepinemab-treated patients experienced a significant increase in brain metabolic activity in regions of interest in the brain, plus the treatment demonstrated protection against brain atrophy, and improved motor and cognitive function.

Vaccinex has released detailed data from the trial, and, since FDG-PET is also a clinically relevant biomarker in Alzheimer's, have used the data to justify its move into Alzheimer's treatment. Again, not being an expert in the underlying science, it is hard to judge the merits of this trial or whether the results justify the significant expenditure. What is evident is that SEMA4D blocking is a highly differentiated approach to treating a devastating disease with no known cure, and we also know that the FDA has awarded Pepinemab a coveted fast track designation, which will make it easier for Vaccinex to make a regulatory submission, possibly - according to the trials' Principal Investigator Andrew S. Feigin, MD - treating the current trial as its pivotal trial.

As with Vaccinex's NSCLC trial, there is potentially enough promising data to continue with the study, but equally, potentially not enough to generate real excitement or support amongst the investment community.

I recently covered another small cap stock, Cassava Sciences, (SAVA), whose stock had collapsed from $10, to $2 based on its inability to successfully convert the early promise of an Alzheimer's treatment into a pivotal trial success. In reality, perhaps it was over-ambitious of Cassava to believe it had a potential Alzheimer's treatment given the long history of failed attempts to develop drugs to treat the disease, and the extraordinarily complex nature of neurodegenerative diseases as a whole. Still, with ongoing funding from the Alzheimer's Association, Cassava is working back through its data to identify areas it can improve upon, and has been rewarded by investors for its efforts, with its shares now trading up 67% at $3.36.

I share this information because I think that Vaccinex may fall into a similar category. Whether Vaccinex has been let down by those responsible for the investor relations side of the business, who have failed to drum up enthusiasm for the work the company's scientists are doing, or whether it is the opposite - Vaccinex's data did not ever really justify a stock market listing - is open to discussion.

What I think is most likely to happen to Vaccinex is that it will not immediately find support either for progressing Pepinemab for NSCLC, or for Huntington's - unless the full data from SIGNAL is exceptional - which is, to my mind, so unlikely that it may as well be discounted. But I don't see this as the end of the company as a going concern, rather I think that it can cut its losses , stop funding trials that burn through >$20m per annum, accept funding from its Alzheimer's backers and continue its research on a smaller scale.

As with Cassava, this would generally support the company's current share price, whose recent spikes I would put down to insider buys rather than new backers or heightened interest in its progress. This thesis does support potential price gains, however, because the company can drip feed its progress to the market without the pressure of having to support an unrealistic valuation, or of having to constantly try to raise funding in the hundreds of millions - as it appears to have attempted, and failed to do with a recent filing for a shelf offering.

I hope I am wrong and the Huntington's trial delivers excellent results, which would be a great coup for the company and its investors, and most importantly for patients suffering from this horrendous disease. But a more realistic scenario sees Vaccinex scaling down its operations and focusing on small wins. That is natural for a drug development company, and with such a strategy in place, it might, down the line, secure the investor goodwill the company needs to start scaling the mountain again.

If you like what you have just read and want to receive at least 4 exclusive stock tips every week focused on Pharma, Biotech and Healthcare, then join me at my marketplace channel, Haggerston BioHealth. Invest alongside the model portfolio or simply access the investment bank-grade financial models and research. I hope to see you there.

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

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Versatile Vaccinex Needs A Trial Or Partner Win, But Scaled Down Operation May Be More Likely - Seeking Alpha

Neuroscience

Mason Slaine Donates $1.5 Million in support of Boca Regional’s Keeping the Promise Capital Campaign – Baptist Health South Florida

June 30th, 2020 Baptist Health South Florida

BOCA RATON, FL June 30, 2020 Boca Raton Regional Hospital has received a significant commitment from Mason Slaine, in the amount of $1.5 million, towards Keeping the PromiseThe Campaign for Boca Raton Regional Hospital. Mason joins other notable philanthropists throughout our community who have generously contributed seven and eight-figure gifts to the capital campaign that now boasts $163 million raised thus far. In recognition of Masons generosity, the new Patient Admissions Area in the new patient tower will be named in his honor.

Mr. Slaine has been an extraordinary advocate and very active in our plans since he became involved with Boca Regional a few short years ago, said Lincoln Mendez, CEO of Boca Raton Regional Hospital. We are delighted to have him as a member of our family, as a Foundation Board member and as a lead donor to our Keeping the Promise campaign.

Slaine has served on both the Executive and Audit Committees since he joined the Boca Raton Regional Hospital Foundation in 2016. His $1.5 million gift is his second major philanthropic effort for Boca Raton Regional Hospital: Mason made a similar generous gift to the Marcus Neuroscience Institute a few years ago. In exchange for that gift, the Courtyard adjacent to the Institute bears his name and welcomes staff and visitors to a convenient and enjoyable outdoor space for a break and some respite.

Our communitys healthcare is vital, and that has been particularly understated in the last few months as we all navigate through COVID-19, said Slaine. I have always believed that Boca Regional is uniquely qualified to provide the highest quality of care we all need. I have personally utilized medical services, as well as family members have been cared for at the Hospital, so the facility and the people hold a special place in my heart. I believe in Keeping the Promise and in the next generation of healthcare it will bring. I am proud to be part of it.

The $250 million Keeping the Promise campaign is the largest campaign in the hospitals history. It is supporting major campus redevelopment plans including at the centerpiece, a new patient tower featuring all new surgical suites, an inviting patient lobby and all private patient rooms exceeding the latest safety standards for patient care. The Marcus Neuroscience Institute staff and capital investments are underway targeting all neuroscience programs with an emphasis on neurovascular/stroke, central nervous system, tumor, spine and epilepsy/seizure disorders. In the current hospital building, all existing rooms will be converted to private in a comprehensive renovation of all patient units. A new 972-car parking garage opened recently and will be connected to the Marcus Neuroscience Institute and the new tower when construction is complete. These investments are the initial steps toward an even broader vision for the campus with greater access points and even more specialties including a new Medical Arts Pavilion with an outpatient surgery center, physician offices and an additional parking garage.

###

About Boca Raton Regional Hospital FoundationThe Boca Raton Regional Hospital Foundation, Inc. is a not-for-profit organization for Boca Raton Regional Hospital. Boca Raton Regional Hospital is an advanced, tertiary medical center (BRRH.com) with 400 beds, 2,800 employees and more than 800 primary and specialty physicians on staff. The Hospital is a recognized leader in Oncology, Cardiovascular Disease and Surgery, Minimally Invasive Surgery, Orthopedics, Womens Health, Emergency Medicine and the Neurosciences, all of which offer state-of-the-art diagnostic and imaging capabilities. The Hospital is a designated Comprehensive Stroke Center by the Florida Agency for Health Care Administration (AHCA). BRRH is recognized in U.S. News & World Reports 2019 2020 Best Hospitals listing as a Top Ranked Regional Hospital, for the fourth consecutive year, and the highest ranked hospital in Palm Beach County. Boca Raton Regional Hospital is a part of Baptist Health South Florida.

Media Contacts:

For Boca Raton Regional Hospital:Michael Mauckermmaucker@brrh.com561-955-4706

For Boca Raton Regional Hospital Foundation:Jennifer Rohloffjrohloff@brrh.com561-955-3329

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Mason Slaine Donates $1.5 Million in support of Boca Regional's Keeping the Promise Capital Campaign - Baptist Health South Florida

Neuroscience

Small RNA regulates tau-related disease | NIA – National Institute on Aging

Sex differences can affect Alzheimers and other neurological disease outcomes. According to an NIA-supported study published in Nature Neuroscience, a small genetic molecule, called a microRNA, regulates some immune cell gene expression and the density of neurotoxic brain tangles in a sex-specific manner.

In Alzheimers disease, the protein tau clumps to form clumps of tangled fibers in the brain. Microglia immune cells of the brain and spinal cord are implicated in the accumulation of tau tangles in the brain. MicroRNAs regulate many of the genes in microglia. Led by researchers at Weill Cornell Medicines Appel Alzheimers Disease Research Institute in New York, the study was aimed at learning whether microglial miRNAs in mouse models regulate microglial gene expression and tau tangle pathology in a sex-specific manner.

Using a specific mouse model representing tau-related neurodegenerative disease, the researchers examined whether male and female microglia respond differently to tau tangles. Although they found that the densities of tau tangles were similar in male and female mice, gene regulation was altered to a far greater extent in the male microglia. These study results suggest sex-specific microglial responses to similar levels of tau tangles.

Using a mouse model that had microglial miRNAs removed, the researchers found sex-dependent differences in both the density of tau tangles and microglial gene regulation. Specifically, in the absence of microglial miRNAs, male mice had a higher density of tau tangles than female mice. In addition, the male microglia had an increased expression of genes involved in inflammation and phagocytosis a major mechanism to remove cell debris as well as genes characteristic of disease-associated microglia (DAMs). The researchers proposed that these differences may be exacerbated by age and tau-related disease, because the DAM genes were not active in younger mice.

The study findings illuminate the role of microglial miRNAs as one of potential key contributors to sex-specific phenotypes observed in neurological diseases. Additional research is needed to further expand the understanding of microglial biology in the context of neurodegenerative diseases.

This research was funded in part by NIA grants 1R01AG054214-01A1, U54NS100717, R01AG051390 and F31AG058505.

These activities relate to NIAs AD+ADRD Research Implementation Milestone 2.D. Create programs in basic, translational and clinical research aimed at comprehensive understanding of the impact of sex differences on the trajectories of brain aging and disease, phenotypes of AD and ADRD risk and responsiveness to treatment.

Reference: Kodama L, et al. Microglial microRNAs mediate sex-specific responses to tau pathology. Nature Neuroscience. 2020;23(2):167-171. doi: 10.1038/s41593-019-0560-7.

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Small RNA regulates tau-related disease | NIA - National Institute on Aging

Neuroscience

June: New research in Brain Pathology | News and features – University of Bristol

Bristol scientists have discovered a novel pathology that occurs in several human neurodegenerative diseases, including Huntingtons disease.

The article, published in Brain Pathology, describes how SAFB1 expression occurs in both spinocerebellar ataxias and Huntington's disease and may be a common marker of these conditions, which have a similar genetic background.

SAFB1 is an important protein controlling gene regulation in the brain and is similar in structure to other proteins associated with neurodegenerative diseases of age. The team, from the University of Bristols Translational Health Sciences, wanted to find out if this protein might be associated with certain neurodegenerative conditions.

The researchers analysed SAFB1 expression in the post-mortem brain tissue of spinocerebellar ataxias (SCAs), Huntingtons disease (HD), Multiple sclerosis (MS), Parkinsons disease patients and controls.

They found that SAFB becomes abnormally expressed in the nerve cells of brain regions associated with SCA and HD. Both of these conditions are associated with a specific pathology, called a polyglutamine expansion (an amino acid repeat), which only occurs in SCAs and HD. The same pathology was therefore not seen in control Parkinson's disease or multiple sclerosis.

These novel findings highlight a previously unknown mechanism causing disease which, importantly, suggests SAFB1 may be a diagnostic marker for polyglutamine expansion diseases, such as HD said lead author, James Uney, Professor of Molecular Neuroscience at the University of Bristol.

We were also able to demonstrate how SAFB1 binds the SCA1 gene with the disease causing polyglutamine expansion (which causes spinocerebellar ataxia 1). As well as identifying a possible diagnostic marker, these findings open up the possibility of developing new therapeutic treatments for these rare but devastating neurodegenerative diseases.

The next step is to establish whether inhibiting SAFB1 expression protects patients.

Professor Uney said there was scope in the future to broaden the study to include other diseases, such as Alzheimer's, disease.

Paper:

'Abnormal expression of the scaffold attachment factor 1 in spinocerebellar ataxias and Huntingtons chorea,'in Brain Pathology.

This workwas supported by the BBSRC and the Medical Research Council, UKRI.

The study was made possible by the Bristol Brain Bank and the MRC-funded London Neurodegenerative Diseases Brain Bank at KCL.

Translational Health Sciences at the University of Bristol

Supported by funders such as the NIHR, the Medical Research Council, and charities such as the Wellcome Trust and British Heart Foundation, our research delivers pioneering treatments for patients and groundbreaking discoveries in basic science, across fields including neuroscience and endocrinology, cardiovascular sciences, and a range of other key areas.

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June: New research in Brain Pathology | News and features - University of Bristol

Neuroscience

Tests of Hearing Could Reveal HIV’s Effects on the Brain – Technology Networks

Even with effective anti-retroviral therapy, patients infected with the Human Immunodeficiency Virus (HIV) sustain central nervous system damage. Whether these problems can be mainly attributed to the disease, its treatments, or the bodys immune responses is still being debated, but detecting these changes early and reliably is difficult.Findings from a new study published in Clinical Neurophysiology, involving a collaborative effort between Dartmouths Geisel School of Medicine and the Auditory Neuroscience Laboratory at Northwestern University, are shedding further light on how the brains auditory system may provide a window into how the brain is affected by HIV.

Weve been performing a variety of hearing tests on an established cohort of HIV-positive patients in Dar es Salaam, Tanzania, says Jay Buckey, Jr., MD, a professor of medicine at Geisel who co-led the study. Initially, we thought wed find that HIV affects the ear, but what seems to be affected is the brains ability to process sound.

To test this hypothesis, the researchers used whats called a speech-evoked frequency-following response (FFR). In this test, brain waves are recorded from scalp electrodes (as in an electroencephalogram) while sounds common to everyday speech, like ba, da, or ga, are played into the ear. This offers an objective, non-invasive way to record brain waves and assess the brains auditory functions.

There are many acoustic ingredients in speech, such as pitch, timing, harmonics, and phrase, says Nina Kraus, PhD, Hugh Knowles Professor of Communication Sciences and Neurobiology at Northwestern, who co-led the study with Buckey. The FFR enables us to play speech sounds into the ear of study participants and figure out how good a job the brain is doing processing these different acoustic ingredients.

When comparing the FFR results of 68 HIV-positive adults to 59 HIV-negative adults, the investigators found that the auditory-neurophysiological responses to certain speech cues were disrupted in HIV-positive adults, even though they performed normally on hearing tests confirming that these hearing difficulties are grounded in the central nervous system.

When the brain processes sound, its not like a volume knob where all of the acoustic ingredients are either processed well or poorly, Kraus explains. With the FFR, were able to see which aspects of auditory processing are affected or diminished and ask, Is there a specific neural signature that aligns itself with HIV?

Thats why the researchers envision the FFR as a viable tool for further understanding not only the mechanisms of brain dysfunction associated with HIV, but also other disorders that affect the brain such as concussion, Alzheimers disease, and the Zika virus infection.

Typically, if you want to assess cognitive function, youre going to do things like have people do math problems, remember a list of words, work on some sort of puzzle or task, or do a drawing, says Buckey. It requires people who are trained in doing this kind of testing, and the tests may be fairly specific to the language people speak and the culture they come from.

Whats significant about our results is that the test doesnt require any actions on the patients part; its recorded passively subjects can even sleep or watch a movie, he says. We think the FFR holds a lot of promise as a way to assess the brain easily and objectively.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Tests of Hearing Could Reveal HIV's Effects on the Brain - Technology Networks

Neuroscience

Nanotechnology applied to medicine: The first liquid retina prosthesis – Science Codex

Genoa (Italy), 29 June 2020 - Researchers at IIT-Istituto Italiano di Tecnologia (Italian Institute of Technology) has led to the revolutionary development of an artificial liquid retinal prosthesis to counteract the effects of diseases such as retinitis pigmentosa and age-related macular degeneration that cause the progressive degeneration of photoreceptors of the retina, resulting in blindness. The study has been published in Nature Nanotechnology: http://www.nature.com/articles/s41565-020-0696-3

The multidisciplinary team is composed by researchers from the IIT's Center for Synaptic Neuroscience and Technology in Genoa coordinated by Fabio Benfenati and a team from the IIT's Center for Nano Science and Technology in Milan coordinated by Guglielmo Lanzani, and it also involves the IRCCS Ospedale Sacrocuore Don Calabria in Negrar (Verona) with the team lead by Grazia Pertile, the IRCCS Ospedale Policlinico San Martino in Genoa and the CNR in Bologna. The research has been supported by Fondazione 13 Marzo Onlus, Fondazione Ra.Mo., Rare Partners srl and Fondazione Cariplo.

The study represents the state of the art in retinal prosthetics and is an evolution of the planar artificial retinal model developed by the same team in 2017 and based on organic semiconductor materials (Nature Materials 2017, 16: 681-689).

The "second generation" artificial retina is biomimetic, offers high spatial resolution and consists of an aqueous component in which photoactive polymeric nanoparticles (whose size is of 350 nanometres, thus about 1/100 of the diameter of a hair) are suspended, going to replace the damaged photoreceptors.

The experimental results show that the natural light stimulation of nanoparticles, in fact, causes the activation of retinal neurons spared from degeneration, thus mimicking the functioning of photoreceptors in healthy subjects.

Compared to other existing approaches, the new liquid nature of the prosthesis ensures fast and less traumatic surgery that consist of microinjections of nanoparticles directly under the retina, where they remain trapped and replace the degenerated photoreceptors; this method also ensures an increased effectiveness.

The data collected show also that the innovative experimental technique represents a valid alternative to the methods used to date to restore the photoreceptive capacity of retinal neurons while preserving their spatial resolution, laying a solid foundation for future clinical trials in humans. Moreover, the development of these photosensitive nanomaterials opens the way to new future applications in neuroscience and medicine.

"Our experimental results highlight the potential relevance of nanomaterials in the development of second-generation retinal prostheses to treat degenerative retinal blindness, and represents a major step forward" Fabio Benfenati commented. "The creation of a liquid artificial retinal implant has great potential to ensure a wide-field vision and high-resolution vision. Enclosing the photoactive polymers in particles that are smaller than the photoreceptors, increases the active surface of interaction with the retinal neurons, allows to easily cover the entire retinal surface and to scale the photoactivation at the level of a single photoreceptor."

"In this research we have applied nanotechnology to medicine" concludes Guglielmo Lanzani. "In particular in our labs we have realized polymer nanoparticles that behave like tiny photovoltaic cells, based on carbon and hydrogen, fundamental components of the biochemistry of life. Once injected into the retina, these nanoparticles form small aggregates the size of which is comparable to that of neurons, that effectively behave like photoreceptors."

"The surgical procedure for the subretinal injection of photoactive nanoparticles is minimally invasive and potentially replicable over time, unlike planar retinal prostheses" adds Grazia Pertile, Director at Operating Unit of Ophthalmology at IRCCS Ospedale Sacro Cuore Don Calabria. "At the same time maintaining the advantages of polymeric prosthesis, which is naturally sensitive to the light entering the eye and does not require glasses, cameras or external energy sources."

The research study is based on preclinical models and further experimentations will be fundamental to make the technique a clinical treatment for diseases such as retinitis pigmentosa and age-related macular degeneration.

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Nanotechnology applied to medicine: The first liquid retina prosthesis - Science Codex

Neuroscience

New Director of Research Computing – University of Arkansas Newswire

University of Arkansas

Donald DuRousseau joins IT Services

DonaldDuRousseaujoinedIT Servicesas director of research computing on June 29.

In this role,DuRousseauwill provide strategic leadership in the areas ofcyberinfrastructuretechnologies and academic research computing services for the university.

DuRousseaubrings 20 years of technology experience including leadership with Cyber Security Education Solutions and George Washington University. He holds an M.B.A. from George Washington University and a B.S. in Computational Neuroscience from the University of California, Berkeley.

"This is a key role for IT Services as we partner with academic leaders on our campus to enhance and support the university'sresearch and discovery goals," said SteveKrogull, interim chief information officer. "Donald's focused experience within academic research will help us meet the needs of our students, faculty and staff in new innovative ways.

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New Director of Research Computing - University of Arkansas Newswire