Citizen science: Giving patients a voice in drug development

citizen science patient voice drug development

There’s a natural tension between wanting the FDA to ensure safety and efficacy before a drug enters the market and wanting to speed up what many view as a glacially slow approval process. The rare disease community tends to fall in the second camp, and has become increasingly vocal in calling for more clinical trials, more flexibility in their design and redefinition of what constitutes a benefit.

ALS advocates, for example, have called for a parallel track, “in which FDA provides an early approval based on limited data, and then continues the learning process in a confirmatory clinical trial and if needed, patient registries to collect additional data from patients receiving the drug outside the clinical trial…”

Recent legislation is encouraging patient engagement in drug development, especially for conditions with profound unmet medical needs. In its 2012 iteration, the Prescription Drug User Fees Act (PDUFA) introduced public meetings to get input from the patient community, captured in a series of informative white papers.

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Getting academic diagnostic discoveries to market: 6 tips from industry

diagnosticsdiagnostics (008) Loading of QIAsymphony platform“Wouldn’t it be great if we could come up with a noninvasive diagnostic assay to detect pancreatic cancer at an earlier, more treatable stage?” asked Lori Aro of Myriad Genetics. Her company has been trying to do so for years. So why hasn’t it happened?

Aro, senior director for new product planning at Myriad, outlined the business obstacles at a recent panel hosted by Boston Children’s Hospital’s Technology and Innovation Office (TIDO).

First, who are the target patients for a pancreatic cancer test? Skinny diabetics, patients with chronic pancreatitis, patients with hereditary cancer risk — or all three? “Those three patient types all sit in different doctor’s offices,” said Aro. Simultaneously reaching endocrinologists, gastroenterologists and high-risk patients would be an insurmountable challenge, Myriad concluded.

Second, the assay would likely need to be validated in all three patient populations, with confirmatory imaging. Could the test populations be large enough to make the results statistically significant?

Third, a new test wouldn’t change care, as there is no treatment for pancreatic cancer. In fact, no current data show that earlier diagnosis improves survival. So who would pay for it?

Aro’s story exemplifies just some of the challenges in developing a new diagnostic test.

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The genetics of early-onset psychosis: Could it aid understanding of schizophrenia?

psychosis schizophrenia
(Thomas Zapata/Wikimedia Commons)

At age six, Matthew (not his real name) began hearing voices coming out of the walls and the school intercom, telling him to hurt himself and others. He saw ghosts, aliens in trees and color footprints. Joseph Gonzalez-Heydrich, MD, a psychiatrist at Boston Children’s Hospital, put Matthew, at age 9, on antipsychotic medications, and the hallucinations stopped.

It’s rare for children so young to have psychotic symptoms. Intrigued, Gonzalez-Heydrich referred Matthew for genetic testing.

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Amblyopia detection: A long climb to market for the Pediatric Vision Scanner

David Hunter Pediatric Vision Scanner
(Photo: Bruce Hunter)

David Hunter, MD, PhD, ophthalmologist-in-chief at Boston Children’s Hospital, is also developer of StrabisPix and BabySee. The Pediatric Vision Scanner received FDA marketing clearance last month.

As a pediatric ophthalmologist, I do my best to assure that every young patient I examine will have a lifetime of perfect sight. The condition that I battle most commonly is amblyopia, or “lazy eye,” in which the eye is healthy but does not develop vision — simply because the brain doesn’t receive proper input when a child’s visual system is “learning” how to see.

When I can diagnose amblyopia early enough, I can treat it with an eye patch or eye drops to block the “good” eye, giving the eye with amblyopia time to catch up. But amblyopia does not fight fairly: about half of affected kids have no visible signs of the condition. As a result, amblyopia silently steals the sight of hundreds of thousands of children — many of whom will never get their vision back because treatment started too late.

It is this problem that inspired me to develop the Pediatric Vision Scanner (PVS).

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Another use for mTOR inhibitors: Preserving vanishing bones in Gorham-Stout syndrome

Gorham Stout rapamycin sirolimus
In Gorham-Stout, lymphatic vessels gone amok eat away at bone. Sirolimus appears to reverse this process.

The mTOR pathway is fundamental to nearly every cell in the body. It drives processes related to cell growth, protein production and metabolism, influencing everything from neurocognition to tumor growth. Because of this broad role, indications for drugs targeting the mTOR pathway are also remarkably broad.

Alexander Malloy, 14, is one of the first patients to benefit from a new use: curbing rapid bone loss in patients with a rare “vanishing bone disease,” or Gorham-Stout syndrome. It was discovered when Alex, who had mild scoliosis, started getting worse. To his parents’ shock, an MRI scan showed he was missing bones in his spine.

Gorham-Stout is actually the result of a rare vascular anomaly.

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Where science connects with care: A Q&A with Leonard Zon

Leonard Zon in the lab

Leonard Zon, MD, is founder and director of the Stem Cell Research Program at Boston Children’s Hospital and an investigator with the Howard Hughes Medical Institute and the Harvard Stem Cell Institute. His laboratory research focuses on stem cell therapies for patients with cancer and blood disorders, using a high-throughput, automated system for screening potential drugs in zebrafish. Zon was cofounder of Scholar Rock and Fate Therapeutics and founder and past president of the International Society for Stem Cell Research.

Your hospital just received a #1 ranking from U.S. News & World Report. What does this mean relative to your role there?

I’ve been at Boston Children’s Hospital for 25 years, and it’s really satisfying to be at the premier institution for clinical care. And we’re very lucky to have one of the premier stem cell programs in the world. I have a strong sense that my impact on society is as a physician-scientist, bringing basic discoveries to the clinic. We’re able to have a huge impact on finding new diagnoses and new therapies for our children.

What inspires you to do your job every day?

As a hematologist I take care of patients who have devastating diseases – a variety of blood diseases and cancer. When I see these children, I’m always wondering, could there be ways to treating them that haven’t been thought of before? Successfully treating a child gives them an entire lifetime of health.

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Hunting rare cancers to ground

rare cancers
(UGREEN 3S / Shutterstock)

As we’ve seen this week on Vector, some rare childhood cancers such as medulloblastoma and neuroblastoma are starting to give up their molecular secrets, raising the possibility (and in medulloblastoma’s case, the reality) of precision treatments. Many cancers, though, are so rare that there aren’t even cell lines in which to study them. Yet they could hold important insights. The first tumor suppressor gene, Rb, was discovered in retinoblastoma, a cancer affecting a mere 500 U.S. children each year.

Doctors often have no clear consensus for diagnosing and treating rare cancers, and outcomes tend to be poor in both children and adults. Andrew Hong, MD, a postdoctoral fellow in the Broad Institute’s Cancer Program and a pediatric oncologist at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, is part of a research team that wants to fix that.

Armed with recent advances in culture technology, the scientists aim to engineer cell lines for as many rare cancers as they can get samples for — and then interrogate them for therapeutic targets. A proof-of-concept published in Nature Communications last month finds a lot of potential in their approach. Read more on Broad Minded, the Broad Institute’s science blog.

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New cancer target, let-7, unifies theories on neuroblastoma’s origins

let7-arrows-target-shutterstock_368341574

Striking the nerve tissue, neuroblastoma is the most common cancer in infants and toddlers. Great strides have been made in its treatment, but advanced cases still are often fatal, and children who survive often face life-long physical and intellectual challenges related to their treatment.

A study published online by Nature last week, led by researchers at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, finds that a microRNA called let-7 is central in curbing neuroblastoma. The study unifies several theories about neuroblastoma and could bring focus to efforts to find a targeted, nontoxic alternative to chemotherapy.

The findings also have implications for other solid tumors in which let-7 is lost, such as Wilms tumor, lung, breast, ovarian and cervical cancers, says first author John Powers, PhD, of the Division of Pediatric Hematology/Oncology at Boston Children’s Hospital.

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Beyond appearances: Molecular genetics revises brain tumor classification and care

What a brain tumor looks like isn’t the best predictor of prognosis. (Jensflorian/Wikimedia Commons)
What a brain tumor looks like isn’t the best predictor of prognosis. (Jensflorian/Wikimedia Commons)

Scott PomeroyScott Pomeroy, MD, PhD, is Neurologist-in-Chief at Boston Children’s Hospital. He practices in the Brain Tumor Center and is a member of the F.M. Kirby Neurobiology Center.

For almost a century, brain tumors have been diagnosed based on their appearance under a microscope and classified by their resemblance to the brain cells from which they are derived. For example, astrocytoma ends with “-oma” to designate that it is a tumor derived from astrocytes. In some cases, especially in children, brain tumors resemble cells in the developing brain and are named for the cells from which they are presumed to arise, such as pineoblastoma for developing cells within the pineal gland or medulloblastoma for developing cells within the cerebellum or brainstem.

In June, the World Health Organization (WHO), which sets the worldwide standard, released an updated brain tumor classification scheme that, for the first time, includes molecular and genetic features.

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When antibiotics fail: A potential new angle on severe bacterial infection and sepsis

bacterial infection sepsisBacterial infections that don’t respond to antibiotics are of rising concern. And so is sepsis — the immune system’s last-ditch, failed attack on infection that ends up being lethal itself. Sepsis is the largest killer of newborns and children worldwide and, in the U.S. alone, kills a quarter of a million people each year. Like antibiotic-resistant infections, it has no good treatment.

Reporting this week in Nature, scientists in Boston Children’s Hospital’s Program in Cellular and Molecular Medicine (PCMM) describe new potential avenues for controlling both sepsis and the runaway bacterial infections that provoke it.

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