Stories about: orphan disease

The ‘de-riskers’: Orphan drug acceleration

De-risking drug development for orphan diseasePerhaps counter-intuitively, rare diseases can present attractive business opportunities for pharmaceutical companies. As discussed previously on Vector, they generally offer:

1) a population of patients with a high, unmet need, greatly lowering the bar to FDA approval

2) a closely networked disease community, greatly lowering the bar to creating disease registries and mounting clinical trials

3) well-studied disease pathways.

Recoiling from expensive failures of would-be blockbuster drugs, companies like Pfizer, Novartis, GlaxoSmithKline, Sanofi, Shire and Roche are embracing rare diseases, despite their small market sizes, because of their much clearer path to clinic. But in the current risk-averse industry environment, some projects are stalling. Industry may need more incentive to jump in—and Cydan Development is basing its business model on providing it.

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10 trends to watch in pediatric medicine: Part 2

Sleuthing out pediatric trendsIn Part 1 last week, Vector took a look at digital health apps, telemedicine, genomics, phenomics and new behavioral diagnostics as transformative trends in pediatrics. This week, we complete our list. These posts will also appear as an article in the fall issue of Children’s Hospitals Today magazine.

6. New pharma research and development (R&D) models

Academic medical centers have always worked with the pharmaceutical industry but never so closely as now. In the old model, industry drove therapeutic development. A company might fund an academic project or supply reagents, but the relationship generally ended with the project (and publication of a paper).

Now, with drug pipelines drying up and R&D costs rising, Big Pharma is under pressure to change. New industry-academia collaborations are forging creative partnerships, altering how both parties do business. The new models are allowing hospital researchers to do what they’ve never done before: take the lead in R&D.

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Using DNA sequencing in medicine: The world starts to figure out how

It’s been more than a decade since the Human Genome Project cracked our genetic code. DNA sequencing is getting cheaper and cheaper. So why isn’t it being used every day in medicine?

The truth is that while we have the technology to blow apart a patient’s DNA and piece it back together, letter by letter, and compare it with normal “reference” DNA, doctors don’t really know what to do with this information. How much of it is really relevant or useful? Should they be giving it back to patients and their families, and how?

Handled badly, the information could do more harm than good. “We don’t want to scare patients for no reason, or for the wrong reason,” says Isaac Kohane, MD, PhD, who chairs the Children’s Hospital Informatics Program.

Seeking a set of best practices for safe, clinically useful genomic sequencing, Boston Children’s Hospital took a crowd-sourcing approach.

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First-ever drug trial reverses some signs of aging in progeria

Trial participant Megan Nighbor (now age 12) in 2008 (courtesy Progeria Research Foundation)

The children came from all over the world: 28 families from 16 countries, speaking over a dozen languages. They faced a grim prognosis: death at an average age of 13 from cardiovascular disease.  Not the congenital heart defects we so commonly see in babies coming to Boston Children’s Hospital, but the kind of disease you might find in an 80-year-old: atherosclerosis, heart attacks, strokes.

The children represented three-quarters of the then-known world population with Hutchinson-Gilford Progeria Syndrome, or progeria—a rare, fatal genetic condition in which children seem to age prematurely. When they began arriving at the Clinical Translational Study Unit at Boston Children’s in 2007, most had already lost body fat and hair, had the thin, tight skin typical of elderly people, and were suffering from hearing loss, osteoporosis, hardening of the arteries, stiff joints and failure to grow.

They came every four months, two flying in per week on the dime of the Progeria Research Foundation (PRF).

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Rebooting Fanconi anemia cells: You have to fix the broken code first

David Williams wants to turn cells from Fanconi anemia (FA) patients into stem-like iPS cells. To do that, though, he needs to get the patients' cells to reboot properly. (_rockinfree/Flickr)

About a decade ago, David Williams, MD, set out to solve a problem. The chief of Dana-Farber/Children’s Hospital Cancer Center’s Hematology/Oncology division wanted to treat Fanconi anemia (FA)—a rare, inherited bone marrow failure disease—using gene therapy. In the process, he’d be able to replace patients’ faulty bone marrow cells with ones corrected for the genetic defect that causes FA.

There was one big problem though. “The main bar to attempting gene therapy in FA is that you need to be able to collect a certain number of blood stem cells from a patient in order to be able to give enough corrected cells back,” he says. “In our early clinical trials, we were unable to provide enough corrected stem cells to reverse the bone marrow failure we see in these patients.”

One way around the supply issue would be to create the necessary blood stem cells from FA patients’ own cells by first reprogramming skin cells into what are called induced pluripotent stem (iPS) cells. Using one of several methods, scientist can reboot mature skin cells into an immature, stem cell-like state—essentially turning the cells’ biological clocks back to a time when they could grow into anything the body might need.

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Rare diseases are not rare — and treatments are coming

Eight percent of Americans name apples as their favorite fruit. About 5 percent of the world population owns a computer and 7 percent are on Facebook. Nine percent own a car. Only 2 percent of adults are natural blondes.

Yet 10 percent of people on this planet have a rare or “orphan” disease. In the U.S., that’s almost 30 million people.

Approximately 7,000 medical conditions have been identified as “rare” – defined by the Orphan Drug Act, passed in 1983, as affecting fewer than 200,000 people in the U.S. Some of these are relatively well known and well studied, such as sickle cell disease or amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease); each affects roughly 30,000 patients in the U.S. Others – like multiminicore myopathy, Diamond Blackfan Anemia or galactosemia – you’re unlikely to have heard of, because they affect only a few hundred or thousand people.

Most of these diseases affect children, often from birth, so at pediatric hospitals, patients suffering from something rare and understudied are actually very common.

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Orphan diseases: Bringing academia, industry, and government into the game

To make headway in translating the growing body of genomic knowledge into new treatments for orphan or rare diseases, we have to bring everyone – academia, industry, government, patients, etc. – into the game. (Navin Rajagopalan/Fotopedia)

“If you build it, he will come,” the ghosts of baseball players past tell a farmer in Field of Dreams. But it’s not that easy. To put people in the seats you have to have all of the right pieces: the right team, including players and managers; the right park, one that works for both the team and the fans; and a passion for being the best at the game.

In the field of rare diseases, not only are institutions like Children’s Hospital Boston stepping up to the plate, but industry and government are joining the game, bringing expertise, guidance and infrastructure. Together, they’re starting to turn basic biomedical discoveries – many made possible only through dedicated patients and their families – into lifesaving treatments.

The shape of the game came into clear view last week at the 2nd Annual Rare Disease Symposium at Children’s. This daylong event, hosted by Children’s Technology Innovation & Development Office (TIDO) and the Manton Center for Orphan Disease Research, united scientists, clinicians, regulators, funders and industry. It showcased not only the depth of the team Children’s has fielded for orphan disease work, but also facilities and support available through industrial and governmental partners to conduct translational research on orphan diseases.

Without a doubt, the word of the day was genomes.

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Children’s partnership with Pfizer: A new way to speed therapeutic development

Over the past nine months, Pfizer has built collaborations with a number of premiere academic medical centers, including Children’s Hospital Boston. Wednesday marked the launch of the Boston branch of Pfizer’s Centers for Therapeutic Innovation (CTI), fostering independent collaborations with seven Boston institutions. The CTI aims to facilitate and support joint drug discovery and development — from the conception of an idea through early clinical trials.

So why is Children’s Hospital Boston, the #1 pediatric hospital in the country with an annual research base of $225 million, entering into a partnership with Pfizer? Simply, Pfizer has complementary knowledge, resources and infrastructure to support a number of our therapeutic projects. Pfizer, and other companies, can help us move early-stage discoveries out of the lab and safely into the clinic more quickly than we could on our own, ultimately supporting our mission.

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Making bone make more bone

Femur bone cross sections from a wild type mouse and a high bone mass (HBM) mouse. The HBM mouse at right has a much larger bone cross section, with greater spacing between the dyes and evidence of trabecular bone in the marrow space.

Work your bones, get more bone. The link between exercise and bone density has been recognized for a long time. It works like this: As you work out, your muscles pull on your bones, causing strain. Cells embedded in the structure of your bones called osteocytes sense the strain and put out a call to other bone cells, osteoblasts, to start churning out proteins and minerals that make your bones denser and stronger. Which is why a history of load- or weight-bearing exercise can help prevent osteoporosis.

What if we could awaken osteocytes artificially, helping adults and children with brittle bone diseases make more of the bone they need? Scientists may be closing in on a way to do this, using a gene called Lrp5 that plays a key role in passing along the biochemical signals that translate strain into bone.

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New opportunities for Angelman

Chromosome 15. Image: Wikimedia Commons

Angelman syndrome (AS) is a rare, neurogenetic condition characterized by severe developmental delay, movement disorder, speech impairment (often with a complete lack of speech) and an unusually happy demeanor. Nearly every individual with AS faces at least two major challenges in their daily life: cognitive or intellectual disability, and movement disorder, usually in the form of ataxic (uncoordinated) gait, unsteadiness, jerky movements or tremors. Seizures are also common, and present a daunting health challenge.

Arising in one out of every 10,000 to 20,000 children from the loss of an enzyme on chromosome 15 called Ube3A, AS falls in the category of orphan diseases: ones that affect fewer than one in 200,000 Americans.  There is no cure for AS, but there are therapies and medications that can help the symptoms. Seizures can be controlled with the right medications, physical therapy can improve ataxia, and speech therapy helps improve communication skills.

Like nearly all orphan diseases, research on AS has historically not been well-funded, but orphan diseases have lately gained growing attention, especially at Children’s Hospital Boston.

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