Failed cancer drug may extend life in children with progeria

child with progeria and damage to cell nucleus
Image: Wikimedia Commons. (Source: The Cell Nucleus and Aging: Tantalizing Clues and Hopeful Promises. Scaffidi P, Gordon L, Misteli T. PLoS Biology Vol. 3/11/2005, e395 doi:10.1371/journal.pbio.0030395)

Hutchinson-Guilford Progeria Syndrome, better known as progeria, is a highly rare genetic disease of premature aging. It takes a cruel toll: Children begin losing body fat and hair, develop the thin, tight skin typical of elderly people and suffer from hearing loss, osteoporosis, hardening of the arteries, stiff joints and failure to grow. They die at an average age of 14½, typically from heart disease resembling that of old age.

An observational study published yesterday in the Journal of the American Medical Association suggests that a drug called lonafarnib, originally developed as a potential cancer treatment, can extend these children’s lives.

Read Full Story | Leave a Comment

Families and data scientists build insights on Phelan-McDermid syndrome

querying stacks of data

This is the third year that Jacob Works has made the trip down to Boston Children’s Hospital from Maine. With research assistant Haley Medeiros, he looks at pictures, answers questions, manipulates blocks and mimes actions like knocking on a door. His father, Travis, and another research assistant look on through a window.

“At first, we had to practically bribe him with an iPad with every task,” Travis says. “This year he’s more excited, because he understands more and is more confident and able to share more.”

Jacob, 11, was diagnosed in 2011 with Phelan-McDermid Syndrome, a rare genetic condition that typically causes children to be born “floppy,” with low muscle tone, and to have little or no speech, developmental delay and, often, autism-like behaviors. At the time, Jacob was one of about 800 known cases. But through chromosomal microarray testing, introduced in just the past decade for children with autism symptoms, more cases are being picked up.

Read Full Story | Leave a Comment

Science Seen: New microscope reveals biological life as you’ve never seen it before

Various images of cells captured by a new microscope reported in Science
A new microscope allows us to see how cells behave in 3D and real time inside living organisms.

Astronomers developed a “guide star” adaptive optics technique to obtain the most crystal-clear and precise telescopic images of distant galaxies, stars and planets. Now a team of scientists, led by Nobel laureate Eric Betzig, PhD, are borrowing the very same trick. They’ve combined it with lattice light-sheet to create a new microscope that’s able to capture real-time, incredibly detailed and accurate images, along with three-dimensional videos of biology on the cellular and sub-cellular level.

The work — a collaboration between researchers at Howard Hughes Medical Institute, Boston Children’s Hospital and Harvard Medical School —  is detailed in a new paper just published in Science.

“For the first time, we are seeing life itself at all levels inside whole, living organisms,” said Tom Kirchhausen, PhD, co-author on the new study, who is a senior investigator in the Program in Cellular and Molecular Medicine at Boston Children’s Hospital and a professor of cell biology and pediatrics at Harvard Medical School (HMS).

“Every time we’ve done an experiment with this microscope, we’ve observed something novel — and generated new ideas and hypotheses to test,” Kirchhausen said in a news story by HMS. “It can be used to study almost any problem in a biological system or organism I can think of.”

Read Full Story | Leave a Comment

News Note: A fresh perspective on RNA with big implications for drug development 

RNA-based drugs are the future of therapeuticsRibonucleic acid, or RNA, has long been underappreciated for its role in gene expression. Until recent years, RNA has been thought of merely as a messenger, shuttling DNA’s instructions to the genetic machinery that synthesizes proteins.

But new discoveries of RNA functions, modifications and its ability to transcribe sections of the genome that were previously considered “junk DNA” has led to the discovery of a huge number of new druggable targets.

These new insights into RNA’s complex purposes have largely been uncovered through ever-increasingly sensitive and affordable sequencing methods. As a result, RNA-based drugs now stand to greatly extend our ability to treat diseases beyond the scope of what’s possible with small molecules and biologics.

Although several RND-based drug approaches have already been established, some barriers still prevent these strategies from working broadly. In a review paper for Nature Structural and Molecular Biology, Judy Lieberman, MD, PhD, of the Program in Cellular and Molecular Medicine of Boston Children’s Hospital, lays out where RNA-based drug development currently stands.

Lieberman, who has helped pioneer the RNA-based drug revolution herself, was the first scientist to show in an animal disease model that small, double-stranded RNAs could be used as drugs and leveraged to knock down genes in cells.

Read Lieberman’s review: “Tapping the RNA world for therapeutics.”

Read Full Story | Leave a Comment

Snaps from the lab: Developing better autism interventions

How can we better understand and support people with autism? And how can we tell if an intervention is working? Those are among the questions being asked in the Faja Laboratory, where Susan Faja, PhD, and her team study social and cognitive development in children, teens and young adults with autism spectrum disorder (ASD), using a variety of tools.

Originally on Snapchat, this video walks through some of these studies, including:

  • Individual Development of Executive Attention (IDEA), looking at executive functioning in 2- to 6-year-olds with autism, developmental disability or no developmental concerns. Executive functions include the ability to plan, manage complex or conflicting information, problem-solve and shift between different rules in different situations. By observing young children while they play hands-on tabletop games, Faja’s team is trying to find out: do kids with autism have problems with executive functioning early on, or do problems emerge later as a result of autism itself? The study is an extension of the ongoing GAMES project for 7- to 11-year-olds, in which children play video games designed to boost their executive functions. Faja is also looking to teach parents to use the games with their children at home.
  • Autism Biomarkers Consortium for Clinical Trials (ABC-CT), a multi-institution study that’s seeking objective, reliable measurements of social function and communication in people with autism. “Language, IQ and social assessments are not so sensitive when you’re looking for changes in autism symptoms, especially subtle ones,” says Faja. So her team is using physiologic measures — like EEGs to measure brain activity and eye-tracking technology to measure visual attention — and correlating them with behavioral and cognitive assessments. The ultimate goal is to validate a set of tools that can be used in clinical trials — and in day-to-day practice — to objectively measure and predict how children with ASD will respond to treatment.​
  • Competence in Romance and Understanding Sexual Health (CRUSH), a new study, will enroll young adults with autism and their parents. The goal is to develop curriculum around dating and sexual health that meets the needs of the ASD population, starting with interviews to determine their needs and interests. No evidence-based curricula currently exist for adults on the spectrum, says Faja.

Learn more about current and future projects in the Faja Lab.

Read Full Story | Leave a Comment

Mutant ferrets and kids with microcephaly shed light on brain evolution

ASPM, ferrets, microcephaly and brain evolution
Fawn Gracey illustration

Mouse brains are tiny and smooth. Ferret brains are larger and convoluted. And ferrets, members of the weasel family, could provide the missing link in understanding how we humans acquired our big brains.

Children with microcephaly, whose brains are abnormally small, have a part in the story too. Microcephaly is notorious for its link to the Zika virus, but it can also be caused by mutations in various genes. Some of these genes have been shown to be essential for growth of the cerebral cortex, the part of our brain that handles higher-order thinking.

Reporting in Nature today, a team led by Christopher A. Walsh, MD, PhD, of Boston Children’s Hospital and Byoung-Il Bae, PhD, at Yale University, inactivated the most common recessive microcephaly gene, ASPM, in ferrets. This replicated microcephaly and allowed the team to study what regulates brain size.

“I’m trained as a neurologist, and study kids with developmental brain diseases,” said Walsh in a press release from the Howard Hughes Medical Institute, which gave him a boost to his usual budget to support this work. “I never thought I’d be peering into the evolutionary history of humankind.”

Read Full Story | Leave a Comment

For biomedicine startups, the road to commercialization is paved with mentors and winds through Boston

the road for biomedicine startups

Marina Freytsis, PhD, supports the Technology and Innovation Development Office (TIDO) at Boston Children’s Hospital in seeking industry partnerships for Boston Children’s technologies and intellectual property.

Last week, Boston Children’s Hospital’s Technology and Innovation Development Office (TIDO) had the privilege of hosting a Boston Biomedical Innovation Center (B-BIC) panel discussion on the path from academia to entrepreneurship. We heard from Jeffrey Arnold (an angel investor), Jonathan Thon (an academic-turned-CEO) and Pamela Silver (an entrepreneurial professor).

My top five takeaways for budding entrepreneurs:

Read Full Story | Leave a Comment

A new tactic for antibiotic-resistant pneumonia: Making neutrophils stronger, but fewer in number

bacterial pneumonia with neutrophils

Antibiotic resistance is a growing threat in bacterial pneumonia. While treatments that stimulate the immune system can help the body fight the invaders, these treatments can also cause inflammation that damages and weakens lung tissue.

Now, research in Science Translational Medicine suggests a way to have the best of both worlds: enhanced bacterial killing with reduced inflammation.

Read Full Story | Leave a Comment

Two-drug approach halts lung tumors by starving them metabolically

(Illustration: Fawn Gracey)

Non-small-cell lung cancer is the leading cause of cancer death in the U.S. Roughly 1 in 4 cases are driven by the mutant KRAS oncogene. Though scientists have tried for more than three decades to target KRAS with drugs, they’ve had little success.

In a new study led by Nada Kalaany, PhD, and colleagues at Boston Children’s Hospital took a different approach, looking at what these deadly lung tumors need metabolically to live and grow. Reporting in the Proceedings of the National Academy of Sciences (PNAS), they show that a combination of two existing drugs can effectively starve tumors in a mouse model.

Read Full Story | Leave a Comment

Zeroing in on the fetal-to-adult hemoglobin switch and a new way to combat sickle cell disease

Normal red blood cell vs. sickle-shaped blood cell, which is found in sickle cell disease
Normal red blood cell vs. sickle-shaped blood cell.

It’s been known for more than 40 years that in rare individuals, lingering production of the fetal form of hemoglobin — the oxygen-transporting protein found in red blood cells — can reduce the severity of certain inherited blood disorders, most notably sickle cell disease and thalassemia. Typically, however, a protein called BCL11A switches off fetal hemoglobin production past infancy, but exactly how this happens has not been well understood until now.

In a new paper in Cell, researchers at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center have revealed how BCL11A controls the switch in the body’s production of fetal hemoglobin to adult hemoglobin. It does so by binding to a DNA sequence — made up of the bases T-G-A-C-C-A — that lies just in front of the fetal hemoglobin genes.

Another approach to curing sickle cell disease is already being evaluated in a new clinical trial at Dana-Farber/Boston Children’s. The novel gene therapy restores fetal hemoglobin production by genetically suppressing BCL11A, which prevents it from blocking fetal hemoglobin production. Learn more.

“Genetically modifying this TGACCA segment could be another possible strategy to cure sickle cell disease by blocking BCL11A’s ability to bind to this DNA site and switch off fetal hemoglobin production,” says Stuart Orkin, MD, senior author on the study.

Read Full Story | Leave a Comment