Wednesday, June 8, 2022
CureVac to Acquire Frame Cancer Therapeutics, Adding Novel Antigen Discovery Platform
CureVac N.V. (NASDAQ:CVAC), a global biopharmaceutical company developing a new class of transformative medicines based on messenger ribonucleic acid ("mRNA"), today announced its acquisition of Frame Cancer Therapeutics, a private company focused on advanced genomics and bioinformatics to identify both unique and shared neoantigens across different cancer types.
"The addition of Frame's technology and talent to CureVac's oncology research complements our ability to identify and validate promising neoantigens for our mRNA cancer vaccine programs," said Franz-Werner Haas, Chief Executive Officer of CureVac. "The bioinformatics platform developed by Frame's researchers has the potential to identify a broad panel of neoantigens that go beyond conventional neoantigens and could strongly increase the likelihood of developing highly effective cancer vaccines. We are excited to join forces with the innovative Frame Cancer Therapeutics team and combine their bioinformatics capabilities with our own mRNA expertise to potentially deliver a new class of cancer vaccines."
Frame's FramePro platform identifies structural changes within the cancer genome that give rise to new open reading frames. These new open reading frames result in novel proteins that are absent in healthy tissues and can thereby be recognized as foreign by the immune system. Although these genetic changes are highly specific to individuals, the resulting neoantigenic proteins may be shared among many patients, potentially enabling development of more broadly applicable cancer vaccines.
Bad dreams could be early warning of Parkinson's
Older adults who start to experience bad dreams or nightmares could be exhibiting the earliest signs of Parkinson's disease, say researchers at the University of Birmingham.
A new study, published in eClinicalMedicine, showed that in a cohort of older men, individuals experiencing frequent bad dreams were twice as likely to be later diagnosed with Parkinson's as those who did not.
Previous studies have shown that people with Parkinson's disease experience nightmares and bad dreams more frequently than adults in the general population, but using nightmares as a risk indicator for Parkinson's has not previously been considered.
Lead author, Dr Abidemi Otaiku, of the University's Centre for Human Brain Health, said: "Although it can be really beneficial to diagnose Parkinson's disease early, there are very few risk indicators and many of these require expensive hospital tests or are very common and non-specific, such as diabetes.
"While we need to carry out further research in this area, identifying the significance of bad dreams and nightmares could indicate that individuals who experience changes to their dreams in older age -- without any obvious trigger -- should seek medical advice."
The team used data from a large cohort study from the USA, which contained data over a period of 12 years from 3818 older men living independently. At the beginning of the study, the men completed a range of questionnaires, one of which included a question about sleep quality.
Participants reporting bad dreams at least once per week were then followed up at the end of the study to see whether they were more likely to be diagnosed with Parkinson's disease.
During the follow-up period, 91 cases of Parkinson's were diagnosed. The researchers found that participants experiencing frequent bad dreams were twice as likely to develop the disease compared to those who did not. Most of the diagnoses happened in the first five years of the study. Participants with frequent bad dreams during this period were more than three times as likely to go on to develop Parkinson's.
The results suggest that older adults who will one day be diagnosed with Parkinson's are likely to begin experiencing bad drams and nightmares a few years before developing the characteristic features of Parkinson's, including tremors, stiffness and slowness of movement.
The study also shows that our dreams can reveal important information about our brain structure and function and may prove to be an important target for neuroscience research.
The researchers plan to use electroencephalography (EEG) to look at the biological reasons for dream changes. They will also look at replicating the findings in larger and more diverse cohorts and explore possible links between dreams and other neurodegenerative diseases such as Alzheimer's.
Story Source:
Materials provided by University of Birmingham. Note: Content may be edited for style and length.
Journal Reference:
- Dr Abidemi I. Otaiku. Distressing dreams and risk of Parkinson's disease: A population-based cohort study. eClinicalMedicine, 2022; 101474 DOI: 10.1016/j.eclinm.2022.101474
3 distinct brain circuits in the thalamus contribute to Parkinson's symptoms
Parkinson's disease is best-known as a disorder of movement. Patients often experience tremors, loss of balance, and difficulty initiating movement. The disease also has lesser-known symptoms that are nonmotor, including depression.
In a study of a small region of the thalamus, MIT neuroscientists have now identified three distinct circuits that influence the development of both motor and nonmotor symptoms of Parkinson's. Furthermore, they found that by manipulating these circuits, they could reverse Parkinson's symptoms in mice.
The findings suggest that those circuits could be good targets for new drugs that could help combat many of the symptoms of Parkinson's disease, the researchers say.
"We know that the thalamus is important in Parkinson's disease, but a key question is how can you put together a circuit that that can explain many different things happening in Parkinson's disease. Understanding different symptoms at a circuit level can help guide us in the development of better therapeutics," says Guoping Feng, the James W. and Patricia T. Poitras Professor in Brain and Cognitive Sciences at MIT, a member of the Broad Institute of Harvard and MIT, and the associate director of the McGovern Institute for Brain Research at MIT.
Feng is the senior author of the study, which appears today in Nature. Ying Zhang, a J. Douglas Tan Postdoctoral Fellow at the McGovern Institute, and Dheeraj Roy, a NIH K99 Awardee and a McGovern Fellow at the Broad Institute, are the lead authors of the paper.
Tracing circuits
The thalamus consists of several different regions that perform a variety of functions. Many of these, including the parafascicular (PF) thalamus, help to control movement. Degeneration of these structures is often seen in patients with Parkinson's disease, which is thought to contribute to their motor symptoms.
In this study, the MIT team set out to try to trace how the PF thalamus is connected to other brain regions, in hopes of learning more about its functions. They found that neurons of the PF thalamus project to three different parts of the basal ganglia, a cluster of structures involved in motor control and other functions: the caudate putamen (CPu), the subthalamic nucleus (STN), and the nucleus accumbens (NAc).
"We started with showing these different circuits, and we demonstrated that they're mostly nonoverlapping, which strongly suggests that they have distinct functions," Roy says.
Further studies revealed those functions. The circuit that projects to the CPu appears to be involved in general locomotion, and functions to dampen movement. When the researchers inhibited this circuit, mice spent more time moving around the cage they were in.
The circuit that extends into the STN, on the other hand, is important for motor learning -- the ability to learn a new motor skill through practice. The researchers found that this circuit is necessary for a task in which the mice learn to balance on a rod that spins with increasing speed.
Lastly, the researchers found that, unlike the others, the circuit that connects the PF thalamus to the NAc is not involved in motor activity. Instead, it appears to be linked to motivation. Inhibiting this circuit generates depression-like behaviors in healthy mice, and they will no longer seek a reward such as sugar water.
Druggable targets
Once the researchers established the functions of these three circuits, they decided to explore how they might be affected in Parkinson's disease. To do that, they used a mouse model of Parkinson's, in which dopamine-producing neurons in the midbrain are lost.
They found that in this Parkinson's model, the connection between the PF thalamus and the CPu was enhanced, and that this led to a decrease in overall movement. Additionally, the connections from the PF thalamus to the STN were weakened, which made it more difficult for the mice to learn the accelerating rod task.
Lastly, the researchers showed that in the Parkinson's model, connections from the PF thalamus to the NAc were also interrupted, and that this led to depression-like symptoms in the mice, including loss of motivation.
Using chemogenetics or optogenetics, which allows them to control neuronal activity with a drug or light, the researchers found that they could manipulate each of these three circuits and in doing so, reverse each set of Parkinson's symptoms. Then, they decided to look for molecular targets that might be "druggable," and found that each of the three PF thalamus regions have cells that express different types of cholinergic receptors, which are activated by the neurotransmitter acetylcholine. By blocking or activating those receptors, depending on the circuit, they were also able to reverse the Parkinson's symptoms.
"We found three distinct cholinergic receptors that can be expressed in these three different PF circuits, and if we use antagonists or agonists to modulate these three different PF populations, we can rescue movement, motor learning, and also depression-like behavior in PD mice," Zhang says.
Parkinson's patients are usually treated with L-dopa, a precursor of dopamine. While this drug helps patients regain motor control, it doesn't help with motor learning or any nonmotor symptoms, and over time, patients become resistant to it.
The researchers hope that the circuits they characterized in this study could be targets for new Parkinson's therapies. The types of neurons that they identified in the circuits of the mouse brain are also found in the nonhuman primate brain, and the researchers are now using RNA sequencing to find genes that are expressed specifically in those cells.
"RNA-sequencing technology will allow us to do a much more detailed molecular analysis in a cell-type specific way," Feng says. "There may be better druggable targets in these cells, and once you know the specific cell types you want to modulate, you can identify all kinds of potential targets in them."
The research was funded, in part, by the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics in Neuroscience at MIT, the Stanley Center for Psychiatric Research at the Broad Institute, the James and Patricia Poitras Center for Psychiatric Disorders Research at MIT, the National Institutes of Health BRAIN Initiative, and the National Institute of Mental Health.
Story Source:
Materials provided by Massachusetts Institute of Technology. Original written by Anne Trafton. Note: Content may be edited for style and length.
Journal Reference:
- Ying Zhang, Dheeraj S. Roy, Yi Zhu, Yefei Chen, Tomomi Aida, Yuanyuan Hou, Chenjie Shen, Nicholas E. Lea, Margaret E. Schroeder, Keith M. Skaggs, Heather A. Sullivan, Kyle B. Fischer, Edward M. Callaway, Ian R. Wickersham, Ji Dai, Xiao-Ming Li, Zhonghua Lu, Guoping Feng. Targeting thalamic circuits rescues motor and mood deficits in PD mice. Nature, 2022; DOI: 10.1038/s41586-022-04806-x
Having had COVID-19 may negatively impact your performance at work
Individuals who contract COVID‐19 often experience memory, attention, and concentration problems, even after recovering from the initial illness. A new study from the University of Waterloo shows individuals who had contracted CCOVID‐19 reported significantly more cognitive failures at work.
“COVID-19 is going to be an ongoing part of life, at least for the foreseeable future,” said James Beck, an associate professor in Waterloo’s Psychology department. “It is now common for people to catch COVID-19, recover, and then return to work. Yet, in our study, people who had contracted COVID-19 reported more difficulties at work, relative to people who had never caught COVID.”
Beck and his graduate student, Arden Flow, collected data from a sample of 94 full-time working adults who either had or had not contracted COVID‐19 at least one month prior to the study. Both groups were matched on key demographic characteristics.
“Relative to the group who had never had COVID-19, the group who had contracted COVID-19 reported more cognitive failures at work, which are defined as problems with memory, attention, and action,” Beck said.
A second finding of the work is that cognitive failures were associated with decreased self-ratings of job performance, as well as increased intentions to voluntarily leave one’s current job.
“These results may have important implications for managers and organizations more broadly,” Beck said. “Individuals returning to work after contracting COVID-19 may experience difficulties returning to their pre-COVID-19 level of performance, and accommodations may be necessary. These accommodations might include reducing workloads, extending deadlines, or providing flexible work arrangements.”
The study, The effects of contracting Covid‐19 on cognitive failures at work: implications for task performance and turnover intentions, authored by Beck and Flow, was recently published in the journal Scientific Reports.