27 Search Results for "Prescription"
Posted on by Dr. Francis Collins
First-term finals are nearly upon us and sadly a disturbing percentage of high school seniors are abusing stimulants Adderall (dextroamphetamine) and Ritalin (methylphenidate), which are prescribed for Attention Deficit Hyperactivity Disorder (ADHD). These drugs increase alertness, attention, and energy the same way cocaine does—by boosting the amount of the neurotransmitter dopamine.
Even though these drugs are legal, they’re quite dangerous if not used properly. Taking high doses can cause irregular heartbeat, heart failure, or seizures. High doses of these stimulants can lead to hostility or feelings of paranoia. So, rather than popping pills, it’s a lot safer—and smarter—to boost your grades the old-school way: by studying.
Posted on by Dr. Francis Collins
Gene editing has shown great promise as a non-heritable way to treat a wide range of conditions, including many genetic diseases and more recently, even COVID-19. But could a version of the CRISPR gene-editing tool also help deliver long-lasting pain relief without the risk of addiction associated with prescription opioid drugs?
In work recently published in the journal Science Translational Medicine, researchers demonstrated in mice that a modified version of the CRISPR system can be used to “turn off” a gene in critical neurons to block the transmission of pain signals . While much more study is needed and the approach is still far from being tested in people, the findings suggest that this new CRISPR-based strategy could form the basis for a whole new way to manage chronic pain.
This novel approach to treating chronic pain occurred to Ana Moreno, the study’s first author, when she was a Ph.D. student in the NIH-supported lab of Prashant Mali, University of California, San Diego. Mali had been studying a wide range of novel gene- and cell-based therapeutics. While reading up on both, Moreno landed on a paper about a mutation in a gene that encodes a pain-enhancing protein in spinal neurons called NaV1.7.
Moreno read that kids born with a loss-of-function mutation in this gene have a rare condition known as congenital insensitivity to pain (CIP). They literally don’t sense and respond to pain. Although these children often fail to recognize serious injuries because of the absence of pain to alert them, they have no other noticeable physical effects of the condition.
For Moreno, something clicked. What if it were possible to engineer a new kind of treatment—one designed to turn this gene down or fully off and stop people from feeling chronic pain?
Moreno also had an idea about how to do it. She’d been working on repressing or “turning off” genes using a version of CRISPR known as “dead” Cas9 . In CRISPR systems designed to edit DNA, the Cas9 enzyme is often likened to a pair of scissors. Its job is to cut DNA in just the right spot with the help of an RNA guide. However, CRISPR-dead Cas9 no longer has any ability to cut DNA. It simply sticks to its gene target and blocks its expression. Another advantage is that the system won’t lead to any permanent DNA changes, since any treatment based on CRISPR-dead Cas9 might be safely reversed.
After establishing that the technique worked in cells, Moreno and colleagues moved to studies of laboratory mice. They injected viral vectors carrying the CRISPR treatment into mice with different types of chronic pain, including inflammatory and chemotherapy-induced pain.
Moreno and colleagues determined that all the mice showed evidence of durable pain relief. Remarkably, the treatment also lasted for three months or more and, importantly, without any signs of side effects. The researchers are also exploring another approach to do the same thing using a different set of editing tools called zinc finger nucleases (ZFNs).
The researchers say that one of these approaches might one day work for people with a large number of chronic pain conditions that involve transmission of the pain signal through NaV1.7. That includes diabetic polyneuropathy, sciatica, and osteoarthritis. It also could provide relief for patients undergoing chemotherapy, along with those suffering from many other conditions. Moreno and Mali have co-founded the spinoff company Navega Therapeutics, San Diego, CA, to work on the preclinical steps necessary to help move their approach closer to the clinic.
Chronic pain is a devastating public health problem. While opioids are effective for acute pain, they can do more harm than good for many chronic pain conditions, and they are responsible for a nationwide crisis of addiction and drug overdose deaths . We cannot solve any of these problems without finding new ways to treat chronic pain. As we look to the future, it’s hopeful that innovative new therapeutics such as this gene-editing system could one day help to bring much needed relief.
 Long-lasting analgesia via targeted in situ repression of NaV1.7 in mice. Moreno AM, Alemán F, Catroli GF, Hunt M, Hu M, Dailamy A, Pla A, Woller SA, Palmer N, Parekh U, McDonald D, Roberts AJ, Goodwill V, Dryden I, Hevner RF, Delay L, Gonçalves Dos Santos G, Yaksh TL, Mali P. Sci Transl Med. 2021 Mar 10;13(584):eaay9056.
 Nuclease dead Cas9 is a programmable roadblock for DNA replication. Whinn KS, Kaur G, Lewis JS, Schauer GD, Mueller SH, Jergic S, Maynard H, Gan ZY, Naganbabu M, Bruchez MP, O’Donnell ME, Dixon NE, van Oijen AM, Ghodke H. Sci Rep. 2019 Sep 16;9(1):13292.
 Drug Overdose Deaths. Centers for Disease Control and Prevention.
Congenital insensitivity to pain (National Center for Advancing Translational Sciences/NIH)
Opioids (National Institute on Drug Abuse/NIH)
Mali Lab (University of California, San Diego)
Navega Therapeutics (San Diego, CA)
NIH Support: National Human Genome Research Institute; National Cancer Institute; National Institute of General Medical Sciences; National Institute of Neurological Disorders and Stroke
Posted on by Dr. Francis Collins
The past several months have shown that most people hospitalized with COVID-19 will get better. As inspiring as it is to see these patients breathe on their own and converse with their loved ones again, we are learning that many will leave the hospital still quite ill and in need of further care. But little has been published to offer a detailed demographic picture of those being discharged from our nation’s hospitals and the types of community-based care and monitoring that will be needed to keep them on the road to recovery.
A recent study in the journal EClinicalMedicine helps to fill in those gaps by chronicling the early COVID-19 experience of three prominent hospitals in the Boston area: Massachusetts General Hospital, Brigham and Women’s Hospital, and Newton-Wellesley Hospital. These data were reported from a patient registry of 247 middle-aged and older COVID-19 patients. The patients were admitted over three weeks last March into one of these hospitals, which are part of New England’s largest integrated health network.
The data confirm numerous previous reports that COVID-19 disproportionately affects people of color. The researchers, led by Jason H. Wasfy and Cian P. McCarthy, Massachusetts General Hospital and Harvard Medical School, Boston, found a large number of their patients were Hispanic (30 percent) or Black (10 percent). Wasfy said these numbers could be driven by many factors, including a low income, more family members living in one home, greater difficulty accessing healthcare, presence of chronic illness (health disparities), and serving as essential workers during the pandemic.
The researchers also tracked the patients after discharge for about 80 days. About a third of patients left the hospital for a post-acute care facility to continue their rehabilitation. After discharge, many required supplemental oxygen (15 percent), tube feeding (9 percent), or treatment with medications including antipsychotics and prescription painkillers (16 percent). About 10 percent were readmitted to the hospital within weeks or months of their initial discharge.
Wasfy and colleagues also found:
· Many patients undergoing treatment were enrolled in Medicaid (20 percent) or both Medicaid and Medicare (12 percent).
· A substantial number also were retired (36 percent) or unemployed (8.5 percent), highlighting the role of non-occupational spread. Many others worked in the hospitality industry, healthcare, or public transportation.
· A large proportion (42 percent) of hospitalized patients required intensive care. The good news is that most of them (86 percent) ultimately recovered enough to be discharged from the hospital. Tragically, 14 percent—34 of 247 people—died in the hospital.
These findings represent hospitals in just one notable American city hard hit early in the pandemic. But they spotlight the importance of public health efforts to prevent COVID-19 among the most vulnerable and reduce its most devastating social impacts. These are critical points, and NIH has recently begun supporting community engagement research efforts in areas hardest hit by COVID-19. With this support and access to needed post-discharge care, we aim to help more COVID survivors stay on the road to a full recovery.
 Early clinical and sociodemographic experience with patients hospitalized with COVID-19 at a large American healthcare system. McCarthy CP et al. EClinicalMedicine. August 19, 2020.
Coronavirus (COVID-19) (NIH)
Massachusetts General Hospital (Boston)
Brigham and Women’s Hospital (Boston)
Newton-Wellesley Hospital (Newton, MA)
Jason Wasfy (Massachusetts General Hospital)