Author: Nancy Fliesler

How the antidepressant ketamine rapidly awakens the brain, and why its effects vary more in women

(CREDIT: NATHALIE PICARD / BOSTON CHILDREN’S HOSPITAL)

In small doses, the anesthetic ketamine is a mildly hallucinogenic party drug known as “Special K.” In even smaller doses, ketamine relieves depression — abruptly and sometimes dramatically, steering some people away from suicidal thoughts. Studies indicate that ketamine works in 60 to 70 percent of people not helped by slower-acting SSRIs, the usual drugs for depression.

Two ketamine-like drugs are in the clinical pipeline, and, as of this week, one appears close to FDA approval. With no significant new antidepressant in more than 30 years, anticipation is high. Yet no one has pinned down how low-dose ketamine works. Studies have implicated various brain neurotransmitters and their receptors — serotonin, dopamine, glutamate, GABA receptors, opioid receptors — but findings have been contradictory.

“We felt it was time to figure this out once and for all,” says neuroscientist Takao Hensch, PhD.

Read Full Story | Leave a Comment

Blood stem cell transplants from any donor, without toxicity?

could stem cell transplants be made nontoxic?
(ADOBE STOCK)

Many blood disorders, immune disorders and metabolic disorders can be cured with a transplant of hematopoietic (blood-forming) stem cells, also known as bone marrow transplant. But patients must first receive high-dose, whole-body chemotherapy and/or radiation to deplete their own defective stem cells, providing space for the donor cells to engraft. These “conditioning” regimens are highly toxic: they wipe out the immune system, raising infection risk, and can cause anemia, infertility, other organ damage and cancers. And when the donor isn’t an exact match, patients’ immune systems must be suppressed for prolonged periods to prevent rejection.

As a result, most patients either don’t receive a transplant or must endure serious side effects. But if two new studies bear out in clinical trials, a far gentler conditioning treatment could enable stem-cell transplants for a much wider range of disorders, even possibly from unmatched donors.

Read Full Story | Leave a Comment

Children raised in institutions have impaired memory and executive functioning at age 16

long-term effects of child institutionalization

An estimated 8 million children worldwide live in institutions where they experience neglect and deprivation. Last fall, a study of children reared in Romanian orphanages reported high levels of mental health problems when they reached adolescence. In particular, they had more difficult behaviors such as rule-breaking, excessive arguing with authority figures, stealing or assaulting peers. But if they were placed early with carefully vetted foster families through the Bucharest Early Intervention Project (BEIP) , these problems were reduced.

A new BEIP study, published yesterday in the Proceedings of the National Academy of Sciences, examined cognitive functioning. It found that institutionalized children, at ages 8 and 16, also have impaired memory and executive functioning compared with peers placed early in foster homes.

Read Full Story | Leave a Comment

Using multiple data streams and artificial intelligence to ‘nowcast’ local flu outbreaks

(PHOTO: ADOBESTOCK)

Because influenza is so contagious, it’s been challenging to track and forecast flu activity in real time as people move about and travel. While the CDC continuously monitors patient visits for flu-like illness in the U.S., its information can lag by up to two weeks. A new study led by the Computational Health Informatics Program (CHIP) at Boston Children’s Hospital combined multiple approaches, providing what appear to be the most accurate local flu predictions to date.

Read Full Story | Leave a Comment

Overriding resistance to epigenetic inhibitors in neuroblastoma: Targeting PI3K

(IMAGE COURTESY NATIONAL CANCER INSTITUTE)

Children’s cancers pose unique challenges. They’re not caused by the same kinds of genetic mutations that cause adult cancers, and only a minority of their mutations can be targeted with drugs. In a recent study, Kimberly Stegmaier, MD, at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and her colleagues systematically deleted every gene in the genome in a number of childhood cancers. This led them to previously unknown — and targetable — genes that help drive tumor growth.

But Stegmaier is also interested in epigenetic regulators — proteins that help control the regulation of genes and contribute to many pediatric cancers. They’re a hot subject of research: Child cancers tend to arise in developing tissues, and epigenetic regulators are active during early development. Clinical trials are starting to test drugs that inhibit epigenetic cancer-promoting factors.

There’s a problem, though: Cancers often become resistant to targeted inhibitors, including epigenetic inhibitors. So, again using genome-wide approaches, Stegmaier set out to find ways to overcome this resistance.

Read Full Story | Leave a Comment

Newborn DNA sequencing finds actionable disease risks in nearly 10% of enrolled babies

BabySeq study sequenced the DNA of 159 newborns
(PHOTO: AdobeStock)

Current newborn screening tests a baby’s blood for several dozen known, treatable conditions. Can full-on DNA sequencing at birth add more benefit? Interpreting sequencing results is complex: having a genetic variant doesn’t always mean having the disease, and many of the conditions identified may not currently be treatable.

To explore what DNA sequencing might turn up, the BabySeq study, an NIH-funded project, was in launched in 2015. A team led by Ozge Ceyhan-Birsoy, PhD of Partners HealthCare and Alan H. Beggs, PhD, now reports the comprehensive results of whole-exome sequencing in 159 infants. Their analysis is published in the American Journal of Human Genetics.

Read Full Story | Leave a Comment

After 80 years, genetic causes of Diamond-Blackfan anemia come into view

Vijay Sankaran, MD and a patient with Diamond-Blackfan anemia
Hematologist Vijay Sankaran with Jack Farwell (PHOTO: MICHAEL GODERRE / BOSTON CHILDREN’S HOSPITAL)

In 1938, Louis K. Diamond, MD, and Kenneth Blackfan, MD, at Boston Children’s Hospital described a severe congenital anemia that they termed “hypoplastic” (literally, “underdeveloped”) because of the bone marrow’s inability to produce mature, functioning red blood cells. Eighty years later, the multiple genetic origins of this highly rare disease, now known as Diamond-Blackfan anemia, or DBA, are finally coming into view.

The largest study to date, published recently in the American Journal of Human Genetics, raises as many questions as it answers. But in the meantime, it provides a genetic explanation for nearly 80 percent of patients.

Read Full Story | Leave a Comment

New angles for blocking Shiga and ricin toxins, and new light on an iconic biological process

Shiga toxin producing E. coli
Shiga-toxin-producing E. coli (IMAGE: JANICE HANEY CARR / USCDC)

Min Dong, PhD, and his lab are world experts in toxins and how to combat them. They’ve figured out how Clostridium difficile’s most potent toxin gets into cells and zeroed in on the first new botulinum toxin identified since 1969. Now, they’ve set their sights on Shiga and ricin toxins, and not only identified new potential lines of defense, but also shed new light on a fundamental part of cell biology: glycosylation.

Read Full Story | Leave a Comment

Reviving fetal hemoglobin in sickle cell disease: First patient is symptom-free

Manny Johnson of Boston, 21, previously required monthly blood transfusions to keep his severe sickle cell disease under control. After receiving a new gene therapy treatment, he’s been symptom-free for six months.

Researchers at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center reported Manny’s case Saturday at the American Society of Hematology meeting in San Diego. Manny is their first patient, and an ongoing clinical trial will treat additional patients between ages 3 and 40.

Read Full Story | Leave a Comment

Microglia in the brain: Which are good and which are bad?

Timothy Hammond studying brain microglia in the Stevens Lab at Boston Children's Hospital
If we see microglia in brain disease, are they part of the problem, or part of the solution? asks Timothy Hammond. (PHOTOS: MICHAEL GODERRE / BOSTON CHILDREN’S HOSPITAL)

Microglia are known to be important to brain function. The immune cells have been found to protect the brain from injury and infection and are critical during brain development, helping circuits wire properly. They also seem to play a role in disease — showing up, for example, around brain plaques in people with Alzheimer’s.

It turns out microglia aren’t monolithic. They come in different flavors, and unlike the brain’s neurons, they’re always changing. Tim Hammond, PhD, a neuroscientist in the Stevens lab at Boston Children’s Hospital, showed this in an ambitious study, perhaps the most comprehensive survey of microglia ever conducted. Published last week in Immunity, the findings open a new chapter in brain exploration.

Read Full Story | Leave a Comment