Regenerative Medicine: The Promise and Peril

Retinal pigment epithelial cells

Caption: Scanning electron micrograph of iPSC-derived retinal pigment epithelial cells growing on a nanofiber scaffold (blue).
Credit: Sheldon Miller, Arvydas Maminishkis, Robert Fariss, and Kapil Bharti, National Eye Institute/NIH

Stem cells derived from a person’s own body have the potential to replace tissue damaged by a wide array of diseases. Now, two reports published in the New England Journal of Medicine highlight the promise—and the peril—of this rapidly advancing area of regenerative medicine. Both groups took aim at the same disorder: age-related macular degeneration (AMD), a common, progressive form of vision loss. Unfortunately for several patients, the results couldn’t have been more different.

In the first case, researchers in Japan took cells from the skin of a female volunteer with AMD and used them to create induced pluripotent stem cells (iPSCs) in the lab. Those iPSCs were coaxed into differentiating into cells that closely resemble those found near the macula, a tiny area in the center of the eye’s retina that is damaged in AMD. The lab-grown tissue, made of retinal pigment epithelial cells, was then transplanted into one of the woman’s eyes. While there was hope that there might be actual visual improvement, the main goal of this first in human clinical research project was to assess safety. The patient’s vision remained stable in the treated eye, no adverse events occurred, and the transplanted cells remained viable for more than a year.

Exciting stuff, but, as the second report shows, it is imperative that all human tests of regenerative approaches be designed and carried out with the utmost care and scientific rigor. In that instance, three elderly women with AMD each paid $5,000 to a Florida clinic to be injected in both eyes with a slurry of cells, including stem cells isolated from their own abdominal fat. The sad result? All of the women suffered severe and irreversible vision loss that left them legally or, in one case, completely blind.

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Clinical Trials: Sharing of Data and Living Up to Our End of the Bargain

Discussing clinical trials

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Today we took a huge step forward in our efforts to make sure that data from biomedical research is shared widely and rapidly. The NIH, in collaboration with our fine colleagues at the U.S. Food and Drug Administration (FDA), and with the valuable input from scientists, patients and other members of the public, has announced the HHS regulation and NIH policy to ensure that information about clinical trials is widely shared. In this blog I want to talk about what this will mean for patients, providers, and researchers. I also want to reflect a bit on how the new regulation and policy fit into our overall efforts to improve clinical trials and data sharing.

Clinical trials are essential for the translation of research advances to new approaches to prevention and treatment. Volunteers who take part in clinical trials often do so with no assurance of personal benefit, but with the expectation that their involvement will add to the growing body of knowledge about health and disease, and thus may help others someday. For that to be realized, all trial results information needs to be publicly reported in a timely fashion—and yet we know that doesn’t always happen. Today’s announcements aim to change that. The HHS regulation issued today, called a “final rule”, describes requirements for registering certain clinical trials and submitting summary results information from these trials to ClinicalTrials.gov, a database managed by NIH’s National Library of Medicine (NLM).

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Gene Drive Research Takes Aim at Malaria

Mosquitoes and a Double HelixMalaria has afflicted humans for millennia. Even today, the mosquito-borne, parasitic disease claims more than a half-million lives annually [1]. Now, in a study that has raised both hope and concern, researchers have taken aim at this ancient scourge by using one of modern science’s most powerful new technologies—the CRISPR/Cas9 gene-editing tool—to turn mosquitoes from dangerous malaria vectors into allies against infection [2].

The secret behind this new strategy is the “gene drive,” which involves engineering an organism’s genome in a way that intentionally spreads, or drives, a trait through its population much faster than is possible by normal Mendelian inheritance. The concept of gene drive has been around since the late 1960s [3]; but until the recent arrival of highly precise gene editing tools like CRISPR/Cas9, the approach was largely theoretical. In the new work, researchers inserted into a precise location in the mosquito chromosome, a recombinant DNA segment designed to block transmission of malaria parasites. Importantly, this segment also contained a gene drive designed to ensure the trait was inherited with extreme efficiency. And efficient it was! When the gene-drive engineered mosquitoes were mated with normal mosquitoes in the lab, they passed on the malaria-blocking trait to 99.5 percent of their offspring (as opposed to 50 percent for Mendelian inheritance).

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Honoring Our Promise: Clinical Trial Data Sharing

Clinical Trials Data Sharing Word CloudWhen people enroll in clinical trials to test new drugs, devices, or other interventions, they’re often informed that such research may not benefit them directly. But they’re also told what’s learned in those clinical trials may help others, both now and in the future. To honor these participants’ selfless commitment to advancing biomedical science, researchers have an ethical obligation to share the results of clinical trials in a swift and transparent manner.

But that’s not the only reason why sharing data from clinical trials is so important. Prompt dissemination of clinical trial results is essential for guiding future research. Furthermore, resources can be wasted and people may even stand to be harmed if the results of clinical trials are not fully disclosed in a timely manner. Without access to complete information about previous clinical trials—including data that are negative or inconclusive, researchers may launch similar studies that put participants at needless risk or expose them to ineffective interventions. And, if conclusions are distorted by failure to report results, incomplete knowledge can eventually make its way into clinical guidelines and, thereby, affect the care of a great many patients [1].

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Print-and-Fold Origami Microscope for 50 cents

Using the Foldscope

Caption: Here I am checking out the Foldscope at the White House Maker Faire on June 18. Very cool!
Credit: Manu Prakash, Stanford

When Stanford University bioengineer Manu Prakash traveled to a mosquito-infested rainforest in Thailand a couple of years ago, he visited a clinic with a sophisticated, $100,000 microscope that sat unused in a locked room. It was then Prakash realized that what global health workers really need is an ultra-low cost, simple-to-use, portable microscope that could be deployed in the field to diagnose disease—and he took it upon himself to develop one!

The result is the Foldscope, a ‘use and throwaway’ microscope that Prakash demonstrated last week at the first-ever Maker Faire at the White House. While I saw many amazing inventions and met many incredible inventors at this event, I came away particularly impressed by the practicality of this device and the ingenuity of its maker.

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