Posted on by James K. Gilman, MD, NIH Clinical Center
Here at the NIH Clinical Center, we are proud to be considered a world-renowned research hospital that provides hope through pioneering clinical research to improve human health. But what you may not know is that our doctors are constantly partnering with public and private sectors to come up with innovative technologies that will help to advance health outcomes.
I’m excited to bring to you a story that is perfect example of the ingenuity of our NIH doctors working with global strategic partners to create potentially life-saving technologies. This story begins during the COVID-19 pandemic with the global shortage of ventilators to help patients breathe. Hospitals had a profound need for inexpensive, easy-to-use, rapidly mass-produced resuscitation devices that could be quickly distributed in areas of critical need.
Through strategic partnerships, our Clinical Center doctors learned about and joined an international group of engineers, physicians, respiratory therapists, and patient advocates using their engineering skills to create a ventilator that was functional, affordable, and intuitive. After several iterations and bench testing, they devised a user-friendly ventilator.
Then, with the assistance of 3D-printing technology, they improved the original design and did something pretty incredible: the team created the smallest single-patient ventilator seen to date. The device is just 2.4 centimeters (about 1 inch) in diameter with a length of 7.4 centimeters (about 3 inches).
A typical ventilator in a hospital obviously is much larger and has a bellows system. It fills with oxygen and then forces it into the lungs followed by the patient passively exhaling. These systems have multiple moving parts, valves, hoses, and electronic or mechanical controls to manage all aspects of the oxygen flow into the lungs.
But our miniature, 3D-printed ventilator is single use, disposable, and has no moving parts. It’s based on principles of fluidics to ventilate patients by automatically oscillating between forced inspiration and assisted expiration as airway pressure changes. It requires only a continuous supply of pressurized oxygen.
The possibilities of this 3D-printed miniature ventilator are broad. The ventilators could be easily used in emergency transport, potentially treating battlefield casualties or responding to disasters and mass casualty events like earthquakes.
While refining a concept is important, the key is converting it to actual use, which our doctors are doing admirably in their preclinical and clinical studies. NIH’s William Pritchard, Andrew Mannes, Brad Wood, John Karanian, Ivane Bakhutashvili, Matthew Starost, David Eckstein, and medical student Sheridan Reed studied and have already tested the ventilators in swine with acute lung injury, a common severe outcome in a number of respiratory threats including COVID-19.
In the study, the doctors tested three versions of the device built to correspond to mild, moderate, and severe lung injury. The respirators provided adequate support for moderate and mild lung injuries, and the doctors recall how amazing it was initially to witness a 190-pound swine ventilated by this miniature ventilator.
The doctors believe that the 3D-printed miniature ventilator is a potential “game changer” from start to finish since it is lifesaving, small, simple to use, can be easily and inexpensively printed and stored, and does not require additional maintenance. They recently published their preclinical trial results in the journal Science Translational Medicine .
The NIH team is preparing to initiate first-in-human trials here at the Clinical Center in the coming months. Perhaps, in the not-too-distant future, a device designed to help people breathe could fit into your pocket next to your phone and keys.
 In-line miniature 3D-printed pressure-cycled ventilator maintains respiratory homeostasis in swine with induced acute pulmonary injury. Pritchard WF, Karanian JW, Jung C, Bakhutashvili I, Reed SL, Starost MF, Froelke BR, Barnes TR, Stevenson D, Mendoza A, Eckstein DJ, Wood BJ, Walsh BK, Mannes AJ. Sci Transl Med. 2022 Oct 12;14(666):eabm8351.
Clinical Center (NIH)
Andrew Mannes (Clinical Center)
Bradford Wood (Clinical Center)
David Eckstein (Clinical Center)
Note: Dr. Lawrence Tabak, who performs the duties of the NIH Director, has asked the heads of NIH’s Institutes and Centers (ICs) to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the 21st in the series of NIH IC guest posts that will run until a new permanent NIH director is in place.
Posted on by Lawrence Tabak, D.D.S., Ph.D.
Opioid use disorders (OUD) now threaten the health and lives of far too many young and adult Americans. While getting treatment is a key first step to recovery, overcoming an opioid addiction often comes with brutal withdrawal symptoms, including bad bouts of insomnia that are often untreatable with traditional prescription sleep medications. These medications act as sedatives, making them unsafe for people in OUD recovery.
But now, researchers have found that an approved drug for insomnia that works differently than other sleep medications could offer some needed help for the sleeplessness that affects those overcoming an opioid addiction . The drug, known as suvorexant (Belsomra ®), was provided in a study to people during and immediately after tapering off opioids, and it allowed them to sleep significantly more during this week-long period. Suvorexant also helped to reduce their opioid withdrawal and craving.
This study, which received support from NIH’s Helping to End Addiction Long-term (HEAL) Initiative certainly offers promising news. The Food and Drug Administration (FDA) approved suvorexant to treat insomnia in 2014, and it is available for off-label use to help people overcoming an OUD.
The good news, however, comes with a major caveat. This early clinical trial had relatively small enrollment numbers, and larger studies are definitely needed to follow up and confirm the initial results.
The latest findings, published in the journal Science Translational Medicine, come from a team at Johns Hopkins University School of Medicine, Baltimore, led by Andrew Huhn. He and colleagues recognized sleep disturbances as a severe problem during recovery. They wondered whether suvorexant might help.
Suvorexant doesn’t actively sedate people like other sleeping medications. Suvorexant works by targeting orexin, a biochemical made in the brain that helps keep you awake . Interestingly, orexin signals also have been implicated in opioid withdrawal symptoms, sleep disturbances, and drug-seeking behaviors.
Thirty-eight people entered the Hopkins study, and 26 completed it. Their average age was about 40, with close to equal numbers of white and Black participants. Most were male, and all were undergoing supervised withdrawal treatment with buprenorphine/naloxone, which is used in combination as a medication-assisted treatment for OUD.
To find out if suvorexant helped, the researchers measured total sleep time nightly using wireless devices that recorded brain activity and movement in people taking either 20 milligrams or 40 milligrams of suvorexant versus a placebo. The researchers also used standard methods to assess symptoms of opioid withdrawal, along with suvorexant’s potential for abuse.
The data showed that people taking suvorexant over four days while tapering off opioids slept about 90 minutes longer per night on average. They also continued to sleep for an extra hour a night on average in the four days following the tapering period. The researchers note that these increases in sleep duration far exceed the American Academy of Sleep Medicine’s threshold for clinically meaningful improvement.
The researchers also didn’t see any differences in adverse events between those taking suvorexant versus a placebo. They also note that the main side effect of suvorexant in general is feeling sleepy the next day as the drug wears off slowly. There also wasn’t any evidence that suvorexant might come with a risk for drug abuse.
However, because the study was small, it lacked the needed statistical power to determine meaningful differences between the two doses of suvorexant. The study also didn’t include many women. But overall, the evidence that suvorexant or even other medications that target orexin could improve OUD treatment appears quite promising.
The NIH’s HEAL Initiative has launched over 600 research projects across the country. These studies cover a range of science and health care needs. But a common thread running through these projects is a desire to enhance the evidence base for lifesaving OUD interventions. Another is a commitment to discover better ways to help people recover from an OUD, and these latest data on suvorexant show this commitment in action.
 Suvorexant ameliorated sleep disturbance, opioid withdrawal, and craving during a buprenorphine taper. Huhn AS, Finan PH, Gamaldo CE, Hammond AS, Umbricht A, Bergeria CL, Strain EC, Dunn KE. Sci Transl Med. 2022 Jun 22;14(650):eabn8238.
 The hypocretin/orexin system. Ebrahim IO, et al. J R Soc Med. 2002 May;95(5):227-30.
SAMHSA’s National Helpline (Substance Abuse and Mental Health Services Administration, Rockville, MD)
Opioids (National Institute on Drug Abuse/NIH)
Andrew Huhn (Johns Hopkins School of Medicine, Baltimore)
NIH Support: National Institute on Drug Abuse
By 2050, the World Health Organization estimates that more than 700 million people—or one in every 10 people around the globe—will have disabling hearing loss. In the United States alone, hearing loss affects an estimated 30 million people . Hearing loss can be frustrating, isolating, and even dangerous. It is also associated with dementia, depression, anxiety, reduced mobility, and falls.
Although hearing technologies, such as hearing aids, have improved, not everyone has equal access to these advancements. In fact, though hearing aids and other assistive devices can significantly improve quality of life, only one in four U.S. adults who could benefit from these devices has ever used one. Why? People commonly report encountering economic barriers, such as the high cost of hearing aids and limited access to hearing health care. For some, the reasons are more personal. They may not believe that hearing aids are effective, or they may worry about a perceived negative association with aging. .
As the lead federal agency supporting research initiatives to prevent, detect, and treat hearing loss, NIH’s National Institute on Deafness and Other Communication Disorders (NIDCD) conducts and funds research that identifies ways to break down barriers to hearing health care. Decades of NIDCD research informed a recent landmark announcement by the Food and Drug Administration (FDA) creating a new category of over-the-counter (OTC) hearing aids. When the regulation takes effect (expected in 2022), millions of people who have trouble hearing will be able to purchase less expensive hearing aids without a medical exam, prescription, or fitting by an audiologist.
This exciting development has been on the horizon at NIDCD for some time. Back in 2009, NIDCD’s Working Group on Accessible and Affordable Hearing Health Care for Adults with Mild to Moderate Hearing Loss created a blueprint for research priorities.
The working group’s blueprint led to NIDCD funding of more than 60 research projects spanning the landscape of accessible and affordable hearing health care issues. One study showed that people with hearing loss can independently adjust the settings  on their hearing devices in response to changing acoustic environments and, when given the ability to control their own hearing aid settings, they were generally more satisfied with the sound of the devices than with the audiologist fit .
In 2017, the first randomized, double-blind, placebo-controlled clinical trial comparing an over-the-counter delivery model  of hearing aids with traditional fitting by an audiologist also found that hearing aid users in both groups reported similar benefits. A 2019 follow-up study  confirmed these results, supporting the viability of a direct-to-consumer service delivery model. A small-business research grant funded by NIDCD led to the first FDA-approved self-fitting hearing aid.
Meanwhile, in 2016, NIDCD co-sponsored a consensus report from the National Academies of Sciences, Engineering, and Medicine (NASEM). The report, Hearing Health Care for Adults: Priorities for Improving Access and Affordability, which was developed by an independent expert panel, recommended that the FDA create and regulate a new category of over-the-counter hearing devices to improve access to affordable hearing aids for adults with perceived mild-to-moderate hearing loss. These devices will not be intended for children or for adults with more severe hearing loss.
In sum, this targeted portfolio of NIDCD-funded research—together with the research blueprint and the NASEM consensus report—provided a critical foundation for the 2021 FDA rule creating the new class of OTC hearing aids. As a result of these research and policy efforts, this FDA rule will make some types of hearing aids less expensive and easier to obtain, potentially improving the health, safety, and well-being of millions of Americans.
Transforming hearing health care for adults in the U.S. remains a public health priority. The NIH applauds the scientists who provided critical evidence leading to the new category of hearing aids, and NIDCD encourages them to redouble their efforts. Gaps in hearing health care access remain to be closed.
The NIDCD actively solicits applications for research projects to fill these gaps and continue identifying barriers to care and ways to improve access. The NIDCD will also continue to help the public understand the importance of hearing health care with resources on its website, such as Hearing: A Gateway to Our World video and the Adult Hearing Health Care webpage.
 Hearing loss prevalence in the United States. Lin F, Niparko J, Ferrucci L. Arch Intern Med. 2011 Nov 14;171(20):1851-1852.
 Research drives more accessible, affordable hearing care. Tucci DL, King K. The Hearing Journal. May 2020.
 A “Goldilocks” approach to hearing aid self-fitting: Ear-canal output and speech intelligibility index. Mackersie C, Boothroyd A, Lithgow, A. Ear and Hearing. Jan 2019.
 Self-adjusted amplification parameters produce large between-subject variability and preserve speech intelligibility. Nelson PB, Perry TT, Gregan M, VanTasell, D. Trends in Hearing. 7 Sep 2018.
 The effects of service-delivery model and purchase price on hearing-aid outcomes in older adults: A randomized double-blind placebo-controlled clinical trial. Humes LE, Rogers SE, Quigley TM, Main AK, Kinney DL, Herring C. American Journal of Audiology. 1 Mar 2017.
 A follow-up clinical trial evaluating the consumer-decides service delivery model. Humes LE, Kinney DL, Main AK, Rogers SE. American Journal of Audiology. 15 Mar 2019.
Adult Hearing Health Care (NIDCD)
[Note: Acting NIH Director Lawrence Tabak has asked the heads of NIH’s Institutes and Centers (ICs) to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the ninth in the series of NIH IC guest posts that will run until a new permanent NIH director is in place.]
Posted on by Dr. Francis Collins
With Omicron now on so many people’s minds, public health officials and virologists around the world are laser focused on tracking the spread of this concerning SARS-CoV-2 variant and using every possible means to determine the effectiveness of our COVID-19 vaccines against it. Ultimately, the answer will depend on what happens in the real world. But it will also help to have a ready laboratory means for gauging how well a vaccine works, without having to wait many months for the results in the field.
With this latter idea in mind, I’m happy to share results of an NIH-funded effort to understand the immune responses associated with vaccine-acquired protection against SARS-CoV-2 . The findings, based on the analysis of blood samples from more than 1,000 people who received the Moderna mRNA vaccine, show that antibody levels do correlate, albeit somewhat imperfectly, with how well a vaccine works to prevent infection.
Such measures of immunity, known as “correlates of protection,” have potential to support the approval of new or updated vaccines more rapidly. They’re also useful to show how well a vaccine will work in groups that weren’t represented in a vaccine’s initial testing, such as children, pregnant women, and those with certain health conditions.
The latest study, published in the journal Science, comes from a team of researchers led by Peter Gilbert, Fred Hutchinson Cancer Research Center, Seattle; David Montefiori, Duke University, Durham, NC; and Adrian McDermott, NIH’s Vaccine Research Center, National Institute of Allergy and Infectious Diseases.
The team started with existing data from the Coronavirus Efficacy (COVE) trial. This phase 3 study, conducted in 30,000 U.S. adults, found the Moderna vaccine was safe and about 94 percent effective in protecting people from symptomatic infection with SARS-CoV-2 .
The researchers wanted to understand the underlying immune responses that afforded that impressive level of COVID-19 protection. They also sought to develop a means to measure those responses in the lab and quickly show how well a vaccine works.
To learn more, Gilbert’s team conducted tests on blood samples from COVE participants at the time of their second vaccine dose and again four weeks later. Two of the tests measured concentrations of binding antibodies (bAbs) that latch onto spike proteins that adorn the coronavirus surface. Two others measured the concentration of more broadly protective neutralizing antibodies (nAbs), which block SARS-CoV-2 from infecting human cells via ACE2 receptors found on their surfaces.
Each of the four tests showed antibody levels that were consistently higher in vaccine recipients who did not develop COVID-19 than in those who did. That is consistent with expectations. But these data also allowed the researchers to identify the specific antibody levels associated with various levels of protection from disease.
For those with the highest antibody levels, the vaccine offered an estimated 98 percent protection. Those with levels about 1,000 times lower still were well protected, but their vaccine efficacy was reduced to about 78 percent.
Based on any of the antibodies tested, the estimated COVID-19 risk was about 10 times lower for vaccine recipients with antibodies in the top 10 percent of values compared to those with antibodies that weren’t detectable. Overall, the findings suggest that tests for antibody levels can be applied to make predictions about an mRNA vaccine’s efficacy and may be used to guide modifications to the current vaccine regimen.
To understand the significance of this finding, consider that for a two-dose vaccine like Moderna or Pfizer, a trial using such correlates of protection might generate sufficient data in as little as two months . As a result, such a trial might show whether a vaccine was meeting its benchmarks in 3 to 5 months. By comparison, even a rapid clinical trial done the standard way would take at least seven months to complete. Importantly also, trials relying on such correlates of protection require many fewer participants.
Since all four tests performed equally well, the researchers say it’s conceivable that a single antibody assay might be sufficient to predict how effective a vaccine will be in a clinical trial. Of course, such trials would require subsequent real-world studies to verify that the predicted vaccine efficacy matches actual immune protection.
It should be noted that the Food and Drug Administration (FDA) would need to approve the use of such correlates of protection before their adoption in any vaccine trial. But, to date, the totality of evidence on neutralizing antibody responses as correlates of protection—for which this COVE trial data is a major contributor—is impressive.
Neutralizing antibody levels are also now being considered for use in future coronavirus vaccine trials. Indeed, for the EUA of Pfizer’s mRNA vaccine for 5-to-11-year-olds, the FDA accepted pre-specified success criteria based on neutralizing antibody responses in this age group being as good as those observed in 16- to 25-year-olds .
Antibody levels also have been taken into consideration for decisions about booster shots. However, it’s important to note that antibody levels are not precise enough to help in deciding whether or not any particular individual needs a COVID-19 booster. Those recommendations are based on how much time has passed since the original immunization.
Getting a booster is a really good idea heading into the holidays. The Delta variant remains very much the dominant strain in the U.S., and we need to slow its spread. Most experts think the vaccines and boosters will also provide some protection against the Omicron variant—though the evidence we need is still a week or two away. The Centers for Disease Control and Prevention (CDC) recommends a COVID-19 booster for everyone ages 18 and up at least six months after your second dose of mRNA vaccine or two months after receiving the single dose of the Johnson & Johnson vaccine . You may choose to get the same vaccine or a different one. And, there is a place near you that is offering the shot.
 Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial.
Gilbert PB, Montefiori DC, McDermott AB, Fong Y, Benkeser D, Deng W, Zhou H, Houchens CR, Martins K, Jayashankar L, Castellino F, Flach B, Lin BC, O’Connell S, McDanal C, Eaton A, Sarzotti-Kelsoe M, Lu Y, Yu C, Borate B, van der Laan LWP, Hejazi NS, Huynh C, Miller J, El Sahly HM, Baden LR, Baron M, De La Cruz L, Gay C, Kalams S, Kelley CF, Andrasik MP, Kublin JG, Corey L, Neuzil KM, Carpp LN, Pajon R, Follmann D, Donis RO, Koup RA; Immune Assays Team§; Moderna, Inc. Team§; Coronavirus Vaccine Prevention Network (CoVPN)/Coronavirus Efficacy (COVE) Team§; United States Government (USG)/CoVPN Biostatistics Team§. Science. 2021 Nov 23:eab3435.
 Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, McGettigan J, Khetan S, Segall N, Solis J, Brosz A, Fierro C, Schwartz H, Neuzil K, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Mascola J, Polakowski L, Ledgerwood J, Graham BS, Bennett H, Pajon R, Knightly C, Leav B, Deng W, Zhou H, Han S, Ivarsson M, Miller J, Zaks T; COVE Study Group. N Engl J Med. 2021 Feb 4;384(5):403-416.
 A government-led effort to identify correlates of protection for COVID-19 vaccines. Koup RA, Donis RO, Gilbert PB, Li AW, Shah NA, Houchens CR. Nat Med. 2021 Sep;27(9):1493-1494.
 Evaluation of the BNT162b2 Covid-19 vaccine in children 5 to 11 years of age. Walter EB, Talaat KR, Sabharwal C, Gurtman A, Lockhart S, Paulsen GC, Barnett ED, Muñoz FM, Maldonado Y, Pahud BA, Domachowske JB, Simões EAF, Sarwar UN, Kitchin N, Cunliffe L, Rojo P, Kuchar E, Rämet M, Munjal I, Perez JL, Frenck RW Jr, Lagkadinou E, Swanson KA, Ma H, Xu X, Koury K, Mather S, Belanger TJ, Cooper D, Türeci Ö, Dormitzer PR, Şahin U, Jansen KU, Gruber WC; C4591007 Clinical Trial Group. N Engl J Med. 2021 Nov 9:NEJMoa2116298.
 COVID-19 vaccine booster shots. Centers for Disease Control and Prevention. Nov 29, 2021.
COVID-19 Research (NIH)
Combat COVID (U.S. Department of Health and Human Services)
Peter Gilbert (Fred Hutchison Cancer Research Center)
David Montefiori (Duke University, Durham, NC)
Adrian McDermott (National Institute of Allergy and Infectious Diseases/NIH)
NIH Support: National Institute of Allergy and Infectious Diseases
Posted on by Dr. Francis Collins
About 20,000 people in the U.S. live with hemophilia A. It’s a rare X-linked genetic disorder that affects predominantly males and causes their blood to clot poorly when healing wounds. For some, routine daily activities can turn into painful medical emergencies to stop internal bleeding, all because of changes in a single gene that disables an essential clotting protein.
Now, results of an early-stage clinical trial, published recently in the New England Journal of Medicine, demonstrate that gene therapy is within reach to produce the essential clotting factor in people with hemophilia A. The results show that, in most of the 18 adult participants, a refined gene therapy strategy produced lasting expression of factor VIII (FVIII), the missing clotting factor in hemophilia A . In fact, gene therapy helped most participants reduce—or, in some cases, completely eliminate—bleeding events.
Currently, the most-common treatment option for males with hemophilia A is intravenous infusion of FVIII concentrate. Though infused FVIII becomes immediately available in the bloodstream, these treatments aren’t a cure and must be repeated, often weekly or every other day, to prevent or control bleeding.
Gene therapy, however, represents a possible cure for hemophilia A. Earlier clinical trials reported some success using benign adeno-associated viruses (AAVs) as the vector to deliver the therapeutic FVIII gene to cells in the liver, where the clotting protein is made. But after a year, those trial participants had a marked decline in FVIII expression. Follow-up studies then found that the decline continued over time, thought to be at least in part because of an immune response to the AAV vector.
In the new study, an NIH-funded team led by Lindsey George and Katherine High of the Children’s Hospital of Philadelphia and the University of Pennsylvania, tested their refined delivery system. High is also currently with Asklepios BioPharmaceutical, Inc., Chapel Hill, NC. (Back in the 1970s, she and I were medical students in the same class at the University of North Carolina.) The study was also supported by Spark Therapeutics, Philadelphia.
Trial participants received a single infusion of the novel recombinant AAV-based gene therapy called SPK-8011. It is specifically designed to produce FVIII expression in the liver. In this phase 1/2 clinical trial, which evaluates the safety and initial efficacy of a treatment, participants received one of four different doses of SPK-8011. Most also received steroids to prevent or treat the presumed counterproductive immune response to the therapy.
The researchers followed participants for a year after the experimental treatment, and all enrolled in a follow-up trial for continued observation. During this time, researchers detected no major safety concerns, though several patients had increases in blood levels of a liver enzyme.
The great news is all participants produced the missing FVIII after gene therapy. Twelve of the 16 participants were followed for more than two years and had no apparent decrease in clotting factor activity. This is especially noteworthy because it offers the first demonstration of multiyear stable and durable FVIII expression in individuals with hemophilia A following gene transfer.
Even more encouraging, the men in the trial had more than a 92 percent reduction in bleeding episodes on average. Before treatment, most of the men had 8.5 bleeding episodes per year. After treatment, those events dropped to an average of less than one per year. However, two study participants lost FVIII expression within a year of treatment, presumably due to an immune response to the therapeutic AAV. This finding shows that, while steroids help, they don’t always prevent loss of a therapeutic gene’s expression.
Overall, the findings suggest that AAV-based gene therapy can lead to the durable production of FVIII over several years and significantly reduce bleeding events. The researchers are now exploring possibly more effective ways to control the immune response to AAV in expansion of this phase 1/2 investigation before pursuing a larger phase 3 trial. They’re continuing to monitor participants closely to establish safety and efficacy in the months and years to come.
On a related note, the recently announced Bespoke Gene Therapy Consortium (BGTC), a partnership between NIH and industry, will expand the refined gene therapy approach demonstrated here to more rare and ultrarare diseases. That should make these latest findings extremely encouraging news for the millions of people born with other rare genetic conditions caused by known alterations to a single gene.
 Multiyear Factor VIII expression after AAV Gene transfer for Hemophilia A. George LA, Monahan PE, Eyster ME, Sullivan SK, Ragni MV, Croteau SE, Rasko JEJ, Recht M, Samelson-Jones BJ, MacDougall A, Jaworski K, Noble R, Curran M, Kuranda K, Mingozzi F, Chang T, Reape KZ, Anguela XM, High KA. N Engl J Med. 2021 Nov 18;385(21):1961-1973.
Hemophilia A (National Center for Advancing Translational Sciences/NIH)
FAQ About Rare Diseases (National Center for Advancing Translational Sciences/NIH)
Lindsey George (University of Pennsylvania, Philadelphia)
Katherine High (University of Pennsylvania)
NIH Support: National Heart, Lung, and Blood Institute