Category Archives: Genetic Medicine

PASADENA, Calif., April 25, 2022 /PRNewswire/ -- Alexandria Real Estate Equities, Inc. (NYSE:ARE) announced financial and operating results for the first quarter ended March 31, 2022.

Key highlights

Operating results

1Q22

1Q21

Total revenues:

In millions

$

615.1

$

479.8

Growth

28.2%

Net (loss) income attributable to Alexandria's common stockholders diluted

In millions

$

(151.7)

$

6.1

Per share

$

(0.96)

$

0.04

Funds from operations attributable to Alexandria's common stockholders diluted, as adjusted

In millions

$

324.6

$

263.0

Per share

$

2.05

$

1.91

Continued strong leasing volume in 1Q22, after a historic year of leasing in 2021

1Q22

Total leasing activity RSF

2,463,438

Leasing of development and redevelopment space RSF

1,439,696

Lease renewals and re-leasing of space:

RSF (included in total leasing activity above)

864,077

Rental rate increases

32.2%

Rental rate increases (cash basis)

16.5%

Excluding short-term renewals executed to allow Bristol-Myers Squibb Company ("BMS") to expand and consolidate into our Alexandria Point development project, described further below:

Rental rate increases

39.8%

Rental rate increases (cash basis)

23.2%

Continued strong net operating income and internal growth

A REIT industry-leading high-quality tenant roster with high-quality revenues and cash flows, strong margins, and operational excellence

Percentage of total annual rental revenue in effect from investment-grade or publicly traded large cap tenants

50%

Occupancy of operating properties in North America

94.7%

Occupancy of operating properties in North America (excluding vacancy at recently acquired properties)

98.6%

(1)

Operating margin

71%

Adjusted EBITDA margin

71%

Weighted-average remaining lease term:

All tenants

7.3

years

Top 20 tenants

10.5

years

(1)

Excludes 1.6 million RSF, or 3.9%, of vacancy at recently acquired properties representing lease-up opportunities that are expected to provide incremental annual rental revenue. Refer to "Occupancy" in our Supplemental Information.

100 Binney Street achieves $1 billion valuation milestone in recapitalization

During 1Q22, we completed the sale of a 70% interest in 100 Binney Street in our Cambridge/Inner Suburbs submarket of Greater Boston for a sales price of $713.2 million, or $2,353 per RSF, at capitalization rates of 3.6% and 3.5% (cash basis), representing an excess of $413.6million above our book value of the 70% interest sold. The sales price at 100% represents a property valuation of $1.02 billion. Proceeds from this sale will be reinvested into our highly leased value-creation pipeline and acquisitions with development and redevelopment opportunities.

Continued high demand drives visibility for future growth aggregating $665 million of incremental annual rental revenue

Our highly leased value-creation pipeline of current and key near-term projects that are under construction or that will commence construction in the next six quarters is expected to generate greater than $665 million of incremental annual rental revenue, primarily commencing from 2Q22 through 1Q25.

Strong and flexible balance sheet with significant liquidity

Continued dividend strategy to share growth in cash flows with stockholders

Common stock dividend declared for 1Q22 of $1.15 per common share, aggregating $4.54 per common share for the twelve months ended March 31, 2022, up 24 cents, or 6%, over the twelve months ended March 31, 2021. Our FFO payout ratio of 57% for the three months ended March31, 2022 allows us to continue to share growth in cash flows from operating activities with our stockholders while also retaining a significant portion for reinvestment.

Key items included in operating results

Key items included in net (loss) income attributable to Alexandria's common stockholders:

(In millions, except per share amounts)

Amount

Per Share Diluted

1Q22

1Q21

1Q22

1Q21

Unrealized losses on non-real estate investments

$ (263.4)

$ (46.3)

$ (1.67)

$ (0.34)

Significant realized gains on non-real estate investments

22.9

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Alexandria Real Estate Equities, Inc., at the Vanguard of the Life Science Industry, Reports: 1Q22 Net Loss per Share - Diluted of $0.96; 1Q22 FFO per...

MONDAY, April 25, 2022 (HealthDay News) -- It's known that certain chronic health conditions up the odds of death from COVID-19. Now, new research identifies another risk factor.

Shorter telomeres are associated with an increased likelihood of death from COVID-19, particularly in older women, researchers say.

Telomeres are protective caps on the end of chromosomes (DNA) that shorten with age. Previous research has linked shorter telomeres with a number of age-related diseases, including cancer and osteoarthritis, and a higher risk of infections.

"Our findings implicate telomere length in COVID-19 mortality and highlight its potential as a predictor of death and severe outcome, particularly in older women," said study co-author Ana Virseda-Berdices, of Health Institute Carlos III in Madrid, Spain.

Virseda-Berdices and colleagues examined how telomere length affects COVID-19 severity. The study included more than 600 adults hospitalized with COVID during the first wave of the pandemic, March to September 2020. Telomere length was measured in patient blood samples taken within 20 days of COVID diagnosis or hospitalization.

The 533 patients who survived had an average age of 67, compared with an average age of 78 among the 75 patients who died from COVID.

Among all patients, shorter telomeres were significantly associated with a higher risk death from COVID-19 at 30 and 90 days after hospital discharge.

Further analyses by age and gender showed that longer telomeres were associated with a 70% lower risk of dying from COVID in all women at 30 days, and a 76% reduced risk of dying from the disease at 90 days.

In women 65 and older, longer telomeres were associated with a 78% lower risk of death from COVID-19 at 30 days, and 81% reduced risk at 90 days.

There were no significant differences in telomere length between men who survived COVID-19 and those who died of the disease, according to the study.

The findings were scheduled for presentation this week at the European Congress of Clinical Microbiology and Infectious Diseases, in Lisbon, Portugal. The meeting ends Tuesday.

"While we do not know the reasons for the strong association found in women, it's possible that the lack of association between telomere length and COVID-19 mortality in men could be due to increased comorbidities and risk factors in men that masked the effect," Virseda-Berdices said in a meeting news release.

"Female patients tend to present with less severe disease and are more likely to survive COVID-19, probably due to fewer lifestyle risk factors and comorbidities than men. Besides aging, telomere dysfunction is also associated with smoking, poor diet, higher body mass index and other factors that promote oxidative stress, chronic inflammation and cancer," Virseda-Berdices added.

The study was observational and does not prove cause and effect, the researchers noted. Research presented at meetings is usually considered preliminary until published in a peer-reviewed medical journal.

More information

There's more on telomeres at the U.S. National Human Genome Research Institute.

SOURCE: European Congress of Clinical Microbiology and Infectious Diseases, news release, April 21, 2022

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Genetic Sign of Aging Linked to Risk of Fatal COVID - HealthDay News

Recently, President Joe Biden announced a new federal goal of reducing the cancer death rate by at least 50% over the next 25 years. Its an audacious goal, and one that I applaud.

According to the CDC, over the past 20 years, cancer death rates have gone down 27%, from 196.5 to 144.1 deaths per 100,000 population. Thats the good news. Now the bad: In 2022, you are no more likely to survive five years with an advanced solid cancer like pancreas or lung cancer than you were when my 1955 model 41D Buick Special rolled off the assembly line in Detroit.

Despite that sobering update on where we really are, I was very encouraged by a few of President Bidens comments. His administration has rightfully targeted the real potential of combining existing drugs for more effective cancer treatments. This has been underutilized, but has great potential if correctly applied.

As Biden noted, we need to be able to determine which treatment combinations work best for a particular person. As it stands, Biden said, we know far too little about why a treatment works in some patients and not in others with the same exact diagnosed cancer.

The presidents realizations are laudable and dovetail nicely with the successes weve had using human tumor testing to select the best chemotherapy drugs and combinations for each patient.

As the president said, drugs that work for one patient may not work for another, even if both patients have exactly the same diagnosis. This is why each patient should be tested to select the most effective and least toxic drug regimen for that individual before initiating treatment. It is an approach that the cancer industry now must adopt.

In order to determine the best combination or sequence of drugs, I believe the cancer industry should apply human tumor explant analyses like our ex vivo analysis of programmed cell death. This provides a dynamic assessment of cancer cell response using each patients living cancer cells to select chemotherapy drugs. While the concept may seem new to some, we have successfully applied this technique in over 10,000 patientsmany with difficult-to-treat cancersand doubled their chance of response.

One reason this works, as the President has noted, is because each cancer patient is unique and the response to therapy is very different from one person to the next. When patients are treated without testing, the treating physicians must rely on general guidelines and protocols that cannot capture each patients individual features.

Ex vivo analysis of programmed cell death is distinctly different from the tests offered by most medical centers that rely upon DNA profiles known as genomic analyses. These use the patients chromosomal material to look for mutations and other changes in each patients gene makeup that might guide drug selection. Although the concept is appealing, in reality, only a minority of patients have genetic changes that can actually be used for therapy.

Each human cancer reflects all of its genes, both mutated and normal, acting together to create what we recognize as a malignant tumor. Only functional analyses can capture each patients tumor in real time and provide insights that can inform drug selection and treatment decisions.

In one study we conducted in metastatic lung cancer where the average response rate is 30% with traditional, generic treatment, patients had a 64.5% (p<0.001) response rate when they received drugs that were selected for them in the laboratory, pushing their survivals from months to years.

The role of the laboratory and functional profiling is to ensure that the most effective, least toxic treatments are selected the first time. This improves the likelihood of response and can help avoid toxic treatment choices when other milder drug combinations appear effective.

The broad application of this technology has the potential to improve patient outcomes, curtail costs, limit futile care and streamline drug development. We agree with President Biden that we need to change the way we treat cancer. Human tumor explant analyses may be just the answer the president is seeking.

Photo: Julio C. Valencia via the National Cancer Institute

The rest is here:
Targeted drug combinations are the next big advance in cancer treatment - MedCity News

Mr. and Mrs. Smith, we finally have an answer for you. The couple, whose real names we are protecting for privacy, looked at me anxiously. I had been evaluating their young daughter, Sally, in my role as a medical geneticist at the Childrens Hospital at Montefiore in the Bronx, a borough of New York City. For years, the Smiths had been searching to learn why Sally was suffering from epilepsy, why she didnt seem to understand them and why she wasnt speaking at 6 years of age. In 2021, they ended up in my clinic.

I decided to send a sample of Sallys blood for whole-exome sequencing, a test that could identify a change in one of her genes that might be responsible for her symptoms. A few weeks later I had the answer.

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Sally has an extremely rare disorder that youve probably never heard of, I told them. Its so rare that it doesnt even have a real name yet. Its called NAA10-related disorder. The family looked at me with blank stares. I took a deep breath and continued.

The NAA10 gene codes for an enzyme that modifies critical proteins, enabling them to function properly. A single change in Sallys NAA10 gene would cause the enzyme to be made incorrectly, resulting in intellectual disability and seizures. The NAA10 gene is located on the X chromosome, which is one of two sex chromosomes in humans.

Males typically carry an X and a Y chromosome, while females usually have two X chromosomes; as a result, boys are usually more severely affected and girls have a less predictable course. I explained to the family that only about 50 other people with NAA10-related disorder have been reported across the globe. They then asked me about treatment. I replied sadly, none. I could see them struggling to wrap their heads around this.

They asked further questions about what might happen to Sally: Will she learn to speak? Will she be able to learn? Will she grow old? I told them that there is not enough experience to accurately predict what Sallys future will look like. Feeling useless, I said, Here is a patient support group that might be helpful. And with nothing more to offer, I added: Ill see you in a year.

Moments like this a long-awaited answer that is met with more bewilderment than relief are not uncommon in the practice of medical genetics. Most people expect that after a long, frustrating search, finding the underlying diagnosis will provide answers and a path forward. But sometimes, in cases like Sallys, the answer simply begets more questions.

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Weve faced these difficult questions as two researchers with decades of experience in rare genetic diseases. One of us is a medical geneticist whose clinical work focuses on the diagnosis and management of individuals with rare genetic disorders; the other is a neuroscientist working to determine how rare genetic diseases impact brain function and possible ways to correct them.

They are called rare diseases, but approximately 350 million people worldwide are living with one.

Most so-called rare diseases are poorly understood and have no treatment. The National Institutes of Health has estimated that there are about 7,000 rare diseases, defined as ones affecting fewer than 200,000 Americans. Many rare diseases, however, are like NAA10-related disorders and affect only a handful of individuals.

Major advances in the precision and speed of gene sequencing technology followed by dramatic reductions in the costs of testing have radically changed how medical genetics clinics function. Next-generation genetic sequencing, which was so expensive just a decade ago that it was used only after all other testing options had been exhausted, is now the go-to test in most clinics.

But while sequencing can provide confirmation of a suspected, well-understood condition, it frequently results in a situation like that faced by the Smiths, where the testing result shows an incredibly rare disorder with little known about it.

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The speed and ease with which modern gene sequencing can generate a diagnosis stand in sharp contrast to the prolonged effort required to understand how the genetic variant causes disease. Humans all have the same 20,000-plus genes, which govern the traits that make us characteristically human, such as a large brain, 10 fingers and round pupils. Changes, or variants, in these genes determine our uniqueness. So while we all have genes that tell our bodies to make hair, variants in these genes can make hair that is straight or curly, brown or red. Some genetic variants, however, change the gene product so significantly that they result in disease.

Unraveling the natural history of a rare condition requires years of focused attention by clinicians and scientists. Researchers like us also work to piece together the complex puzzle of how a rare genetic difference can alter metabolic pathways in the brain, as well as other organs that might be affected.

Over time, a fuller picture of the rare disorder begins to emerge. The role of the gene in normal cells or commoner diseases unfolds, as well as possible therapies. For instance, potential treatments might involve replacing or modifying a gene that isnt properly functioning, infusing a vital enzyme that an individuals body isnt making or prescribing a specialized diet or medications. But before one can determine how to treat a genetic disease, researchers first need to determine what is altered and not working normally. Only after this is understood can we begin to envision treatment.

To provide our patients and their families with more answers, we here at the Albert Einstein College of Medicine have begun a program in which we build what we call Gene Teams. These consist of parents or caregivers, their childs physician and interested scientists and their trainees. These researchers are typically working on deciphering the genes function, its encoded protein or the role the gene or protein plays inside of cells.

We bring all the team members together, and the childs physician outlines what is known about the clinical condition, followed by the parents sharing their childs story. The scientists and their trainees then provide an accessible tutorial to the families about what the gene and its associated protein do in cells. Whenever possible our team also discusses ways by which the condition could be treated.

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These tutorials are the first encounters in ongoing relationships. Remarkably, three different families who were empowered by their Gene Team experience have gone on to establish foundations focused on their childs disease, and they have built networks to other families affected by the same rare condition worldwide. These are the STAR Foundation for SLC17A5, the KARES Foundation for KDM5C and the CACNA1A Foundation. The scientists, too, after the team meetings, have often gone on to build major research projects, some focused on the exact variant observed in the affected child.

We as scientists and our trainees have also been transformed by our involvement with the Gene Teams. Working directly with the families brings real-life experience to our laboratory work and inspires us and other researchers to remember that our work matters not only for expanding scientific knowledge but also for helping families in need.

We have learned that the blank stare experienced in the doctors office following diagnosis of a rare disease can be transformed by empowering families not only with greater knowledge of the involved gene, but also with an understanding that they are not alone and that there can be a more hopeful path forward.

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Why diagnosis isnt the answer when it comes to the rarest of diseases - EastMojo

image:Development of the fetal brain involves the creation and migration of billions of neurons during the course of pregnancy. view more

Credit: Veronika Mertens

The making of a human brain remains a mostly mysterious process that races from an embryonic neural tube to more than 100 billion interconnected neurons in the brain of a newborn. To achieve this marvel of biological engineering, the developing fetal brain must grow, on average, at a rate of roughly 250,000 nerve cells per minute throughout the course of a pregnancy.

These nerve cells are often generated far from where they will eventually reside and function in the new brain, a migration that, while much investigated in animal models using chemical or biological tracers, has never been studied directly in humans. Until now.

In a new paper, published online April 20, 2022 in Nature, scientists at University of California San Diego School of Medicine and Rady Childrens Institute of Genomic Medicine describe novel methods for inferring the movement of human brain cells during fetal development by studying healthy adult individuals who have recently passed away from natural causes.

Every time a cell divides into two daughter cells, by chance, there arise one or more new mutations, which leave a trail of breadcrumbs that can be read out by modern DNA sequencers, said senior author Joseph Gleeson, MD, Rady Professor of Neuroscience at UC San Diego School of Medicine and director of neuroscience research at the Rady Childrens Institute for Genomic Medicine.

By developing methods to read these mutations across the brain, we are able to reveal key insights into how the human brain forms, in comparison with other species.

Although there are 3 billion DNA bases and more than 30 trillion cells in the human body Gleeson and colleagues focused their efforts on just a few hundred DNA mutations that likely arose during the first few cell divisions after fertilization of the embryo or during early development of the brain. By tracking these mutations throughout the brain in deceased individuals, they were able to reconstruct development of the human brain for the first time.

To understand the type of cells displaying these breadcrumb mutations, they developed methods to isolate each of the major cell types in the brain. For instance, by profiling the mutations in excitatory neurons compared with inhibitory neurons, they confirmed the long-held suspicion that these two cell types are generated in different germinal zones of the brain, and then later mix together in the cerebral cortex, the outermost layer of the organ.

However, they also discovered that the mutations found in the left and right sides of the brain were different from one another, suggesting that at least in humans the two cerebral hemispheres separate during development much earlier than previously suspected.

The results have implications for certain human diseases, like intractable epilepsies, where patients show spontaneous convulsive seizures and require surgery to remove an epileptic brain focus, said Martin W. Breuss, PhD, former project scientist at UC San Diego and now an assistant professor at the University of Colorado School of Medicine.

Breuss is co-first author with Xiaoxu Yang, PhD, postdoctoral scholar and Johannes C. M. Schlachetzki, MD, project scientist, both at UC San Diego; and Danny Antaki, PhD, a former postdoctoral scholar at UC San Diego, now at Twist Biosciences.

This study, the authors said, solves the mystery as to why these foci are almost always restricted to one hemisphere of the brain. Applying these results to other neurological conditions could help scientists understand more mysteries of the brain.

Co-authors include: Xin Xu, Changuk Chung, Guoliang Chai, Valentina Stanley, Qiong Song, Traci F. Newmeyer, An Nguyen, Beibei Cao, Jennifer McEvoy-Venneri and Brett R. Copeland, all at UC San Diego and Rady Childrens Institute for Genomic Medicine; Addison J. Lana, Sydney OBrien, Marten A. Hoeksema, Alexi Nott, Martina P. Pasilla, Scott T. Barton, and Christopher K. Glass, all at UC San Diego; Shareef Nahas, Lucitia Van Der Kraan and Yan Ding, Rady Childrens Institute for Genomic Medicine and the NIMH Brain Somatic Mosaicism Network.

Funding for this research came, in part, from the Howard Hughes Medical Institute, the National Institute of Mental Health (grants MH108898, RO1 MH124890, R21 AG070462), the National Institute on Aging (grants RF1 AGO6106-02, R01 AGO56511-02, R01 NS096170-04) and the UC San Diego IGM Genomics Center (S10 OD026929).

To see a video abstract of the research, visit http://www.youtube.com/watch?v=WfrvSYi9M6A.

# # #

20-Apr-2022

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For neurons, where they begin isn't necessarily where they end - EurekAlert

The goal of reaching an era of individualized precision medicine will first require a closer look at the broader population.

The big picture: Large clinical trials and massive databases of de-identified genetic and other health information sometimes from generations of populations are offering scientists and doctors data to decipher why certain individuals have a higher risk of disease or different responses to treatments.

What's happening: There are many institutions gathering this data, including...

What's new: The COVID-19 pandemic led various groups to collectively create large-scale studies to seek safe and effective COVID treatments as rapidly as possible, such as the U.K.'s Recovery trial on more than 47,000 participants and the WHO's Solidarity Therapeutics Trial on 14,200 randomized hospitalized patients globally.

Growing awareness of the problems caused by a lack of diversity in clinical trials and in most genetic databases has led to other changes.

Reality check: Personalized medicine continues to face serious challenges, and has sometimes resulted in deadly missed targets. But many hope accumulating data from large, more diverse trials will help alleviate those issues.

Between the lines: Large cohort studies are one of the key "strategies to be able to understand the risk factors associated with cancer and with other diseases," says Marcia Cruz-Correa, physician-scientist at the University of Puerto Rico Comprehensive Cancer Center.

The bottom line: These massive datasets are expected to help tease out the biological and socioeconomic factors of disease, Oh says. "They're all tied together."

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The power of massive databases and trials to unlock precision medicine - Axios