Editas Rumored to be in “Advanced Discussions” around Potential Sale of Oncology Assets

 CRISPR gene editing leader Editas Medicine often makes biotech headlines for its therapies for sickle cell and retinal diseases. Less often does it make the news for its preclinical cancer pipeline – which could be why the company is reportedly considering a sale of these assets.

Editas is in "advanced discussions" regarding the sale of its preclinical oncology lineup, according to reporting from Endpoints News. When asked to confirm the rumors, Cristi Barnett, VP & head of corporate communications at Editas told BioSpace, “We have long shared our plans to pursue development and commercialization opportunities through partnerships, specifically with oncology and our iNK program.”

Barnett added that with a new leadership team onboard, Editas “undertook a strategic review to inform opportunities.” 

Investors seemed to agree with the notion as Editas stock rose 4.2% following the report. 

Editas has given its C-Suite a makeover this year. In April, the company appointed genetic medicine veteran Gilmore O’Neill as president and CEO.

O’Neill wasted no time in bringing on board Sanofi veteran Baisong Mei to serve as the company’s new chief medical officer. Mei has deep experience in the hemophilia space at both Sanofi and Bayer. He replaced Lisa Michaels, who was terminated by the company in February.

Editas presented data on one of its oncology assets, EDIT-202, last week at the European Society of Gene and Cell Therapy 29th Annual Meeting in Edinburgh, Scotland. EDIT-202 is a gene-edited iPSC-derived NK cell therapy that maintains prolonged persistence, high cytotoxicity and enhanced in vivo control of solid tumors​, according to Editas.

“Currently, there is no change to our program or plans. EDIT-202…is advancing toward IND-enabling studies,” Barnett said. She added that Editas will share additional updates on this program later this year “including additional preclinical data at an upcoming medical meeting.”

Also at ESGCT, Editas presented preclinical data from another program, EDIT-103, which is being developed to treat rhodopsin-associated autosomal dominant retinitis pigmentosa (RHO-adRP), a progressive type of retinal degeneration.

In a non-human primate model, the therapy demonstrated nearly 100% knockout of the endogenous RHO gene. Additionally, the replacement RHO gene produced over 30% of normal RHO protein levels in the treated area of subretinal injection, the company reported.

https://www.biospace.com/article/editas-rumored-to-be-in-advanced-discussions-around-potential-sale-of-oncology-assets/

Implications of monkeypox virus found in testes of nonhuman primate survivors

 For the first time, scientists have detected monkeypox virus in the testes of macaques during the acute phase of infection, according to research published online today in the journal Nature Microbiology. In addition, the team found preliminary evidence of persistent infection in two animals that survived challenge with the virus. Their results highlight the potential for sexual transmission of the virus in humans.

The ongoing 2022 monkeypox outbreak has been linked to sexual contact in patients with laboratory confirmed infection. As the virus can be transmitted through direct contact with bodily fluids and skin lesions, understanding the biology of monkeypox infection of the testes, and virus shedding in semen, has substantial public health implications.

Investigators at the U.S. Army Medical Research Institute of Infectious Diseases, or USAMRIID, performed a retrospective analysis of monkeypox virus infection in archival tissue samples from crab-eating macaques—a widely used nonhuman primate model for studying the disease and evaluating the efficacy of medical countermeasures, such as vaccines and treatments, against monkeypox.

“We examined tissue samples obtained during both the acute phase of the disease, when infection is at its peak, and the convalescent phase, when infection is gradually subsiding,” explained senior author Xiankun (Kevin) Zeng, Ph.D., of USAMRIID. “We detected monkeypox virus in interstitial cells and seminiferous tubules of the testes, as well as the epididymal lumina, which are the sites of sperm production and maturation.”

Importantly, said Zeng, the team also found preliminary evidence of persistent monkeypox virus infection in two convalescent crab-eating macaques that survived challenge with the virus. Using histological analysis to microscopically analyze the disease course in tissue samples, the USAMRIID team discovered that while monkeypox virus was cleared from most organs—and from healed skin lesions—during convalescence, it could be detected for up to 37 days post-exposure in the testes of the macaques.

USAMRIID investigators, led by Zeng, had previously demonstrated that Ebola, Marburg, Nipah, and Crimean-Congo hemorrhagic fever viruses can persist in certain organs of nonhuman primate survivors where the immune system is suppressed. These immune privileged sites, which are similar in humans, include the eyes, brain, and testes.

While close contact through sexual activity has been associated with the spread of monkeypox virus in the current global epidemic, it was unclear whether the virus replicated in the testes or was transmitted via semen.

“Our data provide evidence that monkeypox virus may be shed into semen during both acute and convalescent stages of the disease in crab-eating macaques,” said Zeng. “It seems plausible, therefore, that human transmission in convalescent male patients might occur via semen.” The authors also noted that persistent virus may be cleared over time.

Because this was a retrospective study using archival tissues, virus isolation in semen was not possible, said Jun Liu, Ph.D., the paper’s first author. Further studies are now needed to understand the origins, dynamics and implications of viral DNA shed in semen, as well as to confirm whether semen from convalescent monkeypox patients contains infectious virus—especially after skin lesions heal. 

In addition, according to the authors, the crab-eating macaque model may not fully reflect monkeypox in humans. The animals demonstrate a more severe and lethal disease than that observed in humans, and the incubation period in the animals is shorter. Furthermore, this study used samples from animals exposed to different viral isolates than the strain currently circulating.  

USAMRIID has decades of experience working with monkeypox and related high-threat pathogens. Among the Institute’s many contributions to the field are a novel respiratory model for monkeypox that closely approximates human exposure and clinical disease; the Phase 3 clinical trial supporting U.S. Food and Drug Administration licensure of the JYNNEOS (Bavarian Nordic) vaccine for preventing smallpox and monkeypox in humans; and initial screening and preclinical efficacy testing of TPOXX (SIGA Technologies), the first drug approved for treatment of smallpox. USAMRIID continues to develop monoclonal antibodies and other approaches to protect against orthopoxviruses.  

About the U.S. Army Medical Research Institute of Infectious Diseases:
Since 1969, USAMRIID has provided leading edge medical capabilities to deter and defend against current and emerging biological threat agents. The Institute is the only laboratory in the Department of Defense equipped to safely study highly hazardous viruses requiring maximum containment at Biosafety Level 4. Research conducted at USAMRIID leads to vaccines, drugs, diagnostics, and training programs that protect both Warfighters and civilians. The Institute's unique science and technology base serves not only to address current threats to our Armed Forces but is an essential element in the medical response to any future biological threats that may confront our nation. For more information, visit https://usamriid.health.mil/. 

Reference: 
Retrospective detection of monkeypox virus in the testes of nonhuman primate survivors. Nature Microbiology: 17 Oct. 2022. https://www.nature.com/articles/s41564-022-01259-w
DOI: 10.1038/s41564-022-01259-w

Authors:
Jun Liu, Eric M. Mucker, Jennifer L. Chapman, April M. Babka, Jamal M. Gordon, Ashely V. Bryan, Jo Lynne W. Raymond, Todd M. Bell, Paul R. Facemire, Arthur J. Goff, Aysegul Nalca, and Xiankun Zeng

https://www.eurekalert.org/news-releases/967977

After lifetime of blindness, newly sighted can immediately identify human locomotion

 Humans are highly sensitive to the bodily movement of other people. Our ability to comprehend body language is crucial to our social thriving, providing information on emotion and behavioral predictions through subtle cues.

When and how do we develop the ability to recognize human movement and distinguish it from other forms of movement? Newborns only 2 days old can tell apart random movement patterns and coordinated animal-like motion. But the ability to differentiate between the bodily movement of humans and other animals is reported to appear only approximately five months after birth. Many researchers therefore believe that babies learn to recognize human locomotion during these first months through repeated visual exposure.

A new study by MIT researchers suggests that a rethinking may be in order. The study is part of Project Prakash, a program dedicated to treating early-onset blindness in children and young adults that was founded by Pawan Sinha, a professor in MIT's Department of Brain and Cognitive Sciences (BCS). Surgeries conducted at Dr. Shroff's Charity Eye Hospital in New Delhi, India, allow patients to start seeing late in life. Alongside the project's humanitarian goal, patients suffering from significantly obstructing cataracts since birth also participate in studies on the development of sight. Such research among patients who gain sight late in life unlocks new methods for studying the development of visual processing.

In a paper published in Neuropsychologia, researchers from MIT, Project Prakash, and York University sought to establish whether the ability to identify human movement relies on extensive visual exposure. The study included two participants, 7 and 20 years old, both almost entirely blind since birth, who were able to perceive only light strong enough to pass through their dense cataracts. As part of the study, the participants watched videos displaying patterns of light representing the coordinated movements of walking humans, pigeons, and cats, as well as similar patterns of movement lacking the shape of these animals' body structure. They were then asked to describe what they saw.

The patients watched the videos in several instances before and after the cataract removal. Before the removal, the blind subjects could see the lights only when looking up close, centimeters away from the monitor. Yet they could not ascribe any meaning to these patterns, which seemed to them merely random movements of lights with no coherent pattern or overall structure.

Immediately after surgery, as the patients' clarity of sight improved, they could better make out visual details. In their very first minutes of exposure to unobstructed sight, the two patients identified the light patterns representing human locomotion. They both did so six out of eight times. They also successfully identified human movement patterns even when these were flipped upside down. At this early stage, however, they recognized only human locomotion with the configuration of a human body structure. Moreover, they did not recognize patterns of animal locomotion at all.

"Patients who had very limited exposure to human bodily movement before the cataract removal, could recognize it for the first time immediately after the removal, once their vision was good enough to see details. This result suggests that extensive visual exposure is not critical for the ability to identify human motion," says Shlomit Ben-Ami, a Project Prakash researcher and a former MIT postdoc now at Tel Aviv University, who spearheaded the study. "The fact that the participants could recognize human movement upside down strengthens the idea that visual experience may not be central to acquiring this visual capacity."

The researchers are exploring possible accounts for why the participants were able to identify human locomotion but not the movement of other animals. One hypothesis they are considering is that learning to interpret the bodily movement of other humans may be based partly on familiarity with one's own body movements and structure. This hypothesis may explain why after the surgery, the participants did not recognize animal locomotion but only human movement—and only as long as it had the configuration of a human body.

"We should be wary of jumping to conclusions about the underlying mechanism here," Ben-Ami says. "While the results are suggestive, they need to be verified with a larger participant pool. This study wasn't designed for answering which mechanism explains the process by which we learn to identify human movement. It is also important to remember that the patients, who were blind most of their lives, didn't go through the normal development of vision. So they may be able to utilize the knowledge of their bodily movements as a resource more efficiently than other people."

"This study addresses a very interesting question in vision: what are the starting dispensations in our developmental progressions, and how are they instantiated?" says Sinha, the study's senior author. "It is gratifying that Project Prakash has provided us an opportunity to grapple with this and many other questions about how the brain learns to do vision. I look forward to further work that can help test the intriguing findings thus far."

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Movement can help with the processing of visual information

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More information: Shlomit Ben-Ami et al, Human (but not animal) motion can be recognized at first sight—After treatment for congenital blindness, Neuropsychologia (2022). DOI: 10.1016/j.neuropsychologia.2022.108307

https://medicalxpress.com/news/2022-10-lifetime-newly-sighted-immediately-human.html

How virus attacks cat kidney, could jump to humans

 In a study published this week in the Proceedings of the National Academy of Sciences, virologists from the University of Pittsburgh Center for Vaccine Research reverse-engineered an elusive virus linked to chronic kidney disease in cats and described its mechanism of infection, outlining its potential to infect people.

The research suggested that the feline morbillivirus, or FeMV, uses the same mechanism of cell entry and infection as other viruses in the morbillivirus family, such as measles. However, unlike measles, FeMV appears to spread from host to host through urine in a similar way to the zoonotic Nipah virus harbored in bats, which causes annual deadly outbreaks in humans across Southeast Asia.

The study provides the first clear insight into this understudied virus and its potential trajectory from infecting animals to jumping into humans.

"Feline morbillivirus stayed under the radar for many years," said senior author Paul Duprex, Ph.D., director of the Center for Vaccine Research at Pitt's School of Medicine. "By understanding the genetics of a virus that was challenging to grow in the laboratory, we are now able to shine light on its connection to chronic kidney disease and better understand how we can stop transmission and potential spillover into human populations."

First discovered in stray cats in Hong Kong a decade ago, FeMV has since been found in domestic cats across Asia and Europe and identified and fully sequenced in the U.S. in 2016 by Duprex's research team when they worked in Boston. While previous studies have linked FeMV infections to chronic kidney disease in cats—one of the leading causes of death in older animals—the new study shows in unprecedented detail how the virus gets to the kidneys.

Similar to other members of the same viral family, FeMV enters cells by binding to a surface protein receptor called CD150. Related viruses, including measles, use CD150 as their primary entry receptor, and people who are vaccinated against measles are protected from getting infected with FeMV. The eradication of measles, however, might present an evolutionary opportunity for other morbilliviruses, such as FeMV, to seek new hosts and jump into unvaccinated people.

"That's why illuminating animal diseases proactively matters," said Duprex. "Preparedness is vital in heading off an epidemic."

By creating a genetically modified version of FeMV containing a fluorescent probe, researchers were able to track its spread throughout cells and organs, discovering that its transmission can be halted by inhibiting a class of protein-cleaving enzymes called cathepsins. Interestingly, cathepsins are mostly used by Nipah viruses but not the morbilliviruses, suggesting that FeMV is an evolutionary intermediate between the two viral families.

"It's important to understand the pathogens of animals because those can become the pathogens of people," said Duprex. "Learning about the viruses that infect cats is not only important for reducing the rates of kidney failure in our beloved pets, but also helps us understand something new about emerging infectious diseases and how they can spread across different animal species. There are about 85 million cats in the U.S. and over half a billion in the world. We live with them in close proximity, and their health matters."

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Emerging significance of gammaherpesvirus and morbillivirus infections in cats

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More information: Sham Nambulli et al, FeMV is a cathepsin-dependent unique morbillivirus infecting the kidneys of domestic cats, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2209405119

https://medicalxpress.com/news/2022-10-scientists-illuminate-virus-cat-kidney.html

Intuitive Q3 beats views

 Intuitive Surgical (NASDAQ:ISRG) reported on Tuesday third quarter earnings that beat analysts' forecasts and revenue that topped expectations.

Intuitive Surgical announced earnings per share of $1.19 on revenue of $1.56B. Analysts polled by Investing.com anticipated EPS of $1.12 on revenue of $1.51B.

Intuitive Surgical shares are down 5% from the beginning of the year, still down 47.60% from its 52 week high of $369.69 set on November 5, 2021.

https://www.investing.com/news/stock-market-news/intuitive-surgical-earnings-revenue-beat-in-q3-2915273

Intuitive Surgical started at Overweight by Barclays

 Target $235

https://finviz.com/quote.ashx?t=ISRG&p=d

Sleep brainwaves provide a powerful new tool for understanding disease

 A team led by researchers from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, in close collaboration with investigators at Mass General Hospital and Beth Israel Deaconess Medical Center has developed a powerful computational tool for understanding brain health and disease, providing an enhanced way of characterizing the activity of the brain during sleep. The researchers devised a new method that extracts tens of thousands of electrical events from the brainwaves of a sleeping person. Information from these waveforms is then used to create a picture of brain activity that seems to act like a fingerprint -- unique for each person and consistent from one night to the next. They then used their approach to identify new potential biomarkers in the brain activity of people with schizophrenia. Their findings are published in the journal, SLEEP. Postdoctoral fellow, Patrick Stokes, PhD, was the first author on the study and the senior author was Michael Prerau, PhD, associate neuroscientist and the director of the Neurophysiological Signal Processing Core in the Division of Sleep and Circadian Disorders at the Brigham.

"This work expands the way we can look at brain activity during sleep," said Prerau. "By moving beyond traditional notions that break up the complex continuum of sleep into specific categories and waveform classes, we can reveal new types of signals and dynamics that may be important for understanding brain health and disease."

Scientists typically study brain activity during sleep using the electroencephalogram, or EEG, which measures brainwaves at the scalp. Starting in the mid 1930s, the sleep EEG was first studied by looking at the traces of brainwaves drawn on a paper tape by a machine. Many important features of sleep are still based on what people almost a century ago could most easily observe in the complex waveform traces. Even the latest machine learning and signal processing algorithms for detecting sleep waveforms are judged against their ability to recreate human observation. In this study, the researchers asked: What can we learn if we expand our notion of sleep brainwaves beyond what was historically easy to identify by eye?

One particularly important set of sleep brainwave events are called sleep spindles. These spindles are short oscillation waveforms, usually lasting less than 1-2 seconds, that are linked to our ability to convert short-term memories to long-term memories. Changes in spindle activity have been linked with numerous disorders such as schizophrenia, autism, and Alzheimer's disease, as well as with natural aging. In this study, rather than looking for spindle activity according to the historical definition, the team developed a new approach to automatically extract tens of thousands of short spindle-like waveform events from the EEG data throughout the entire night. Next, instead of looking at the waveforms in terms of fixed sleep stages (i.e., Wake, REM, and non-REM stages 1-3) as standard sleep studies do, they characterized the full continuum of gradual changes that occur in the brain during sleep. Using all these data, the team created graphical representations called slow oscillation power and phase histograms, which provide a powerful visualization of the activity of all the waveforms as a function of continuous sleep depth and synchronized activity in the cortex. "This further demonstrates the richness of the information that traditional, manual scoring leaves on the table," said co-author Shaun Purcell, PhD, of the Department of Psychiatry at the Brigham.

When the team looked at a group of healthy participants, each with two nights of sleep recordings, the patterns observed appeared to be almost like fingerprints -- highly specific to each person with strong consistency across nights. These results suggest new ways in which brain activity differs from person to person, even within groups of healthy people selected as control groups. The researchers then compared the activity between the healthy subjects and a population of people with schizophrenia, a disorder that reduces spindle activity. Using their approach, the team not only saw the known differences in participants with schizophrenia, but also found differences in other spindle-like waveforms occurring at other frequencies in the brain. This suggests new potential EEG biomarkers of schizophrenia that could be useful in better understanding the mechanisms of the disorder and in the development of targeted treatments.

"This approach is really exciting," said co-author Dara Manoach, PhD, of the Department of Psychiatry at Massachusetts General Hospital. "We look forward to seeing how we can enhance our understanding, not only of schizophrenia, but also of other neurodevelopmental disorders characterized by differences in sleep, such as autism and pediatric epilepsy."

"We are just starting to understand the scope of neurodiversity that exists within the general population," said Prerau. "If we can more accurately characterize the individual differences observed in both neurological health and disease, we can work towards improved diagnostics and treatments."

Co-authors were Preetish Rath, Tom Possidente, Mingjian He, Shaun Purcell, Dara Manoach, and Robert Stickgold. Michael Prerau was the senior author.

This work was supported by the National Institute of Neurological Disorders and Stroke (R01NS096177) and the National Institute of Aging (R01AG054081 (MJP).

Story Source:

Materials provided by Brigham and Women's Hospital. Note: Content may be edited for style and length.

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Journal Reference:

1. Patrick A Stokes, Preetish Rath, Thomas Possidente, Mingjian He, Shaun Purcell, Dara S Manoach, Robert Stickgold, Michael J Prerau. Transient Oscillation Dynamics During Sleep Provide a Robust Basis for Electroencephalographic Phenotyping and Biomarker Identification. Sleep, 2022; DOI: 10.1093/sleep/zsac223

https://www.sciencedaily.com/releases/2022/10/221018131133.htm