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The Michael J. Fox Foundation (MJFF) has introduced a series of educational videos about Parkinson’s disease, as well as a video offering advice to those caring for people with the disorder. November is National Caregivers Month.
Called the Whiteboard Series, the short illustrated segments are designed to enhance understanding of Parkinson’s and current research activity, the MJFF said in a press release. It also is designed to motivate the Parkinson’s community to get involved.
Up to a million people in the United States live with Parkinson’s, according to the first video, and about 60,000 new cases are diagnosed annually. Although age increases the risk of developing the disease — average age at diagnosis is 60 — some patients are younger than 40.
The segment discusses the need for laboratory tests and other diagnostic tools, saying that physicians currently rely on medical histories and exams, looking for classic motor symptoms such as resting tremor, stiffness and slowness of movement. The video also points out that, beyond walking and balance problems, Parkinson’s can also cause constipation, sleep issues, cognitive changes, depression, and loss of the sense of smell.
While each patient has a unique case and mix of symptoms, all patients have in common the loss of dopamine cells, which coordinate movement and enable feelings of motivation and reward, the video explains.
While some researchers think Parkinson’s is likely caused by a combination of genetics and environmental factors, no straight line can be drawn between cause and effect. Still, according to the segment, genetics research offers the best opportunity to discover paths to treatment.
The video also discusses the need for individualized treatment regimens, and encourages patients to use the Foundation’s 360 Toolkit, which offers advice on living with Parkinson’s.
Another video briefly unspools the complexity of drug development. For example, the video states that it takes more than $1 billion and up to 30 years to bring to market a single central nervous system drug. Even after a series of research steps culminating in clinical trials, only one in 12 prospective drugs is ultimately proven safe and beneficial to patients. The video also discusses the foundation’s research investments and priorities.
The segment on genetics centers around the foundation’s belief that advances arising from genetics research offer some of the best chances of developing therapies to help Parkinson’s patients. It also includes stories from patients who have undergone genetic testing.
The final segment, narrated by a journalist who has Parkinson’s, urges patients to participate as research volunteers. Currently, fewer than one in 10 do. Because 85 percent of clinical trials face delays, and 30 percent don’t get off the ground, many more volunteers are needed, the segment states.
In a separate video called “Ask the MD: Caregiving in Parkinson’s Disease,” Rachel Dolhun, a neurologist and movement disorder specialist who is the foundation’s vice president of medical communications, offers advice for caregivers, including maintaining open lines of communication, staying organized, making sure the patient’s home is safe, and considering other living arrangements before patients can no longer be cared for safely at home.
Dolhun also offers self-care tips for those living with Parkinson’s patients, including maintaining independence, taking breaks, establishing strong support systems, knowing limitations, and prioritizing one’s own health.
The foundation funds research aimed at the development of improved therapies for Parkinson’s patients, as well as ultimately curing the disease.
I was working as a crisis clinician when the twin towers fell. My colleagues and I saw an increase in the number of people needing help with anxiety-related mental health issues. Sheldon Solomon, PhD, explained this phenomenon with his terror management theory – which is concerned with how humans manage threats to our survival, both real and imagined.
Parkinson’s disease (PD) threatens and terrorizes me. This “disease thief” invades my mind, body, and home — and there is nothing I can do to stop it. I live with the fear of knowing that it will show up each year and take something else from me.
This disease thief has taken my three careers: professional geologist/scientist, therapist, and professor. It took away my favorite hobby, rock collecting. I suffered significant losses of income, social networking, and personal identity. My careers represented a large part of how I saw myself in society.
I retrained and now use a computer to continue my connection with my former careers. While it’s not the same as face-to-face, I’m using some of the skills I’ve acquired over the years so I can still teach. Yet, as I continue to reshape my identity, I fear the disease thief lurking in the shadows waiting to invade my life again.
(Graphic art by Dr. C)
In the past, I actively practiced being centered and calm. Until recently, I’d never felt terrorized or anxious, except for a short time in active combat in Vietnam. Stress has a way of exaggerating emotions, and life has been quite stressful over the past few years. We moved into a new home, had to leave our pets behind, and had trouble finding quality neurologists to treat the unique form of PD that I have. At one time, it looked like everything would fall apart. I felt that my survival was at risk.
I tend to feel things intensely; I cry at movies and feel other people’s pain as if it were my own. I am an empath, and I wrote my PhD dissertation on advanced levels of empathy. PD changes the emotional filters and alters the perception of reality connected to those emotions. It’s another aspect of scenario looping breakdown.
Dealing with the disease thief requires terror management.
Following are the steps I take:
1. With intense emotion, good or bad, stop and breathe.
2. Do not act on the emotion.
3. Do not spin in thought around the emotion.
I begin these steps as soon as possible after the emotion hits. If I wait too long, the risk of emotional dysfunction increases. If I do nothing, emotional noise will rush in to fill the void. I follow the steps with meditation. When I am calm, I can rationally examine the emotive events.
Being terrorized by the disease thief is one example of exaggerated emotions. Many situations produce emotions, and with PD, emotions are exaggerated. My quality of life is linked to my ability to manage my emotions. It is part of my rehab plan, which includes mental attentiveness, recognizing triggers, rest, exercise, and avoidance of particular foods or chemicals. With this plan in place, I’m ready to confront the disease thief.
***
Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.
October 19, 2018 by Sarah Haurin, Duke Research Blog
Only cells expressing the HaloTag receptor can bind to the AMPA-repressing drug, ensuring virtually perfect cell-type specificity. Credit: Duke Research Blog
The brain is the body's most complex organ, and consequently the least understood. In fact, researchers like Michael Tadross, MD, PhD, wonder if the current research methods employed by neuroscientists are telling us as much as we think.
Current methods such as gene editing and pharmacology can reveal how certain genes and drugs affect the cells in a given area of the brain, but they're limited in that they don't account for differences among different cell types. With his research, Tadross has tried to target specific cell types to better understand mechanisms that cause neuropsychiatric disorders.
To do this, Tadross developed a method to ensure a drug injected into a region of the brain will only affect specific cell types. Tadross genetically engineered the cell type of interest so that a special receptor protein, called HaloTag, is expressed at the cell membrane. Additionally, the drug of interest is altered so that it is tethered to the molecule that binds with the HaloTag receptor. By connecting the drug to the Halo-Tag ligand, and engineering only the cell type of interest to express the specific Halo-Tag receptor, Tadross effectively limited the cells affected by the drug to just one type. He calls this method "Drugs Acutely Restricted by Tethering," or DART.
Tadross has been using the DART method to better understand the mechanisms underlying Parkinson's disease. Parkinson's is a neurological disease that affects a region of the brain called the striatum, causing tremors, slow movement, and rigid muscles, among other motor deficits.
Patients with Parkinson's show decreased levels of the neurotransmitter dopamine in the striatum. Consequently, treatments that involve restoring dopamine levels improve symptoms. For these reasons, Parkinson's has long been regarded as a disease caused by a deficit in dopamine.
With his technique, Tadross is challenging this assumption. In addition to death of dopaminergic neurons, Parkinson's is associated with an increase of the strength of synapses, or connections, between neurons that express AMPA receptors, which are the most common excitatory receptors in the brain.
In order to simulate the effects of Parkinson's, Tadross and his team induced the death of dopaminergic neurons in the striatum of mice. As expected, the mice displayed significant motor impairments consistent with Parkinson's. However, in addition to inducing the death of these neurons, Tadross engineered the AMPA-expressing cells to produce the Halo-Tag protein.
Tadross then treated the mice striatum with a common AMPA receptor blocker tethered to the Halo-Tag ligand. Amazingly, blocking the activity of these AMPA-expressing neurons, even in the absence of the dopaminergic neurons, reversed the effects of Parkinson's so that the previously affected mice moved normally.
Tadross's findings with the Parkinson's mice exemplifies how little we know about cause and effect in the brain. The key to designing effective treatments for neuropsychiatric diseases, and possibly other diseases outside the nervous system, may be in teasing out the relationship of specific types of cells to symptoms and targeting the disease that way.
The ingenious work of researchers like Tadross will undoubtedly help bring us closer to understanding how the brain truly works.
ONO-2160 is a new drug being developed for the treatment of Parkinson's Disease. It also includes carbidopa, which is the same as is included in Sinemet. ONO-2160 is an L-dopa pro-drug, which means that once absorbed it is converted into L-dopa.
An open study clinical trial was carried out on people with Parkinson's Disease in which ONO-2160 and carbidopa was compared to the use of L-dopa and carbidopa, which is what is in Sinemet.
Patients were primarily evaluated using the Unified Parkinson's Disease Rating Scale Part III, a Parkinson's disease symptom diary, and analysis of adverse events. Pharmacokinetic analysis of plasma levodopa concentration was also performed. ONO-2160 and carbidopa therapy stabilized the plasma concentration of L-dopa better than L-dopa with carbidopa. No adverse events with safety concerns were observed.
The combination of ONO-2160 and carbidopa produced a prolonged and stable plasma L-dopa concentration whilst also reducing the Parkinson's Disease symptom scores. The combination was well tolerated with no safety concerns. The results suggest an improved method of administering L-dopa.
Russell Kern, executive vice president and chief scientific officer of International Stem Cell Corp. (International Stem Cell Corp.)
International Stem Cell Corp. has given its Parkinson’s disease therapy to the 10th patient in an Australian clinical trial, the Carlsbad company said earlier this month.
The patient received brain cells derived from the company’s proprietary stem cell product, introduced into the brain. The surgery was performed at the Royal Melbourne Hospital in Melbourne, Australia, where a subsidiary is conducting the trial.
While similar transplants have been performed using fetal brain cells, International Stem Cell uses its own proprietary cells. So patients getting this experimental therapy are being carefully examined for any dangerous side effects.
The latest patient was the second of three groups of Parkinson’s patients. Each group has received varying doses of the cells. This group is getting 70 million cells, the highest dose yet given.
The last patient in the group is expected to be treated by the end of this year, the company said.
“Based on the available clinical data, we are confident that the therapy is safe, well-tolerated, and can potentially improve the quality of life of the patients," said Russell Kern, the company’s executive vice president and chief scientific officer, in the statement.
The early stage study is mainly meant to judge safety in treating the movement disorder. The company said earlier this year that there have been preliminary signs that treated patients are showing benefit. But this will need to be confirmed with more advanced studies.
International Stem Cell’s treatment is derived from unfertilized or parthenogenetic human egg cells. These are grown into neural stem cells, capable of becoming various kinds of cells in the brain. They have been immune-matched so there’s a reduced chance of being rejected.
After transplantation, the neural stem cells are intended to mature into types of cells that will relieve symptoms. Some are expected to become neurons that make the neurotransmitter dopamine; cells that are destroyed in Parkinson’s. Others are expected to become cells that support the dopamine-making neurons.
Another effort in San Diego County, Summit For Stem Cell, is attempting a somewhat similar therapy. One major difference is that the cells are derived from the patients to be treated, which makes them immune-compatible. These are grown into stem cells, then those cells are converted into dopamine-making neurons. Only these dopamine-making cells are transplanted.
More information on International Stem Cell’s Parkinson’s program is available on the company’s website at http://internationalstemcell.com.
For the first time, the Federal Trade Commission has cracked down onstem cell clinicsfor overzealous marketing claims, filing a complaint against two California clinics that promoted their treatments for everything from autism to Parkinson’s despite a lack of evidence.
As part of a proposed settlement announced Thursday, the FTC is requiring the clinics — Regenerative Medical Group and Telehealth Medical Group — and their owner, Dr. Bryn Jarald Henderson, to stop making such claims and to inform past and current patients about the settlement.
In the complaint, the FTC accused Henderson and his clinics of implying or directly saying that their treatments could help patients with a range of diseases even though there was no indication that was the case. The agency also cited the companies for describing their treatments as comparable to or better than approved or studied treatments.
The clinics, both in Orange, Calif., touted the “miracles” made possible by the amniotic stem cells they used. Ads and promotional materials claimed the cells could “reverse autism symptoms” and enabled a “101 year old Lady once blind for 7 years” to see again. The clinics also claimed the cells could treat cerebral palsy, Parkinson’s disease, and chronic kidney disease.
“Until recently, it was believed that damaged brain tissue is a permanent condition,” read one piece of marketing tied to treatment for stroke recovery. “Nowadays the re-growth of brain cells and improvements of neurological function has been documented. Stem Cell treatment acts as a form of medical time machine, reversing the damage that has already been made.”
As the FTC complaint states: “There are no human clinical studies in the scientific literature showing that amniotic stem cell therapy cures, treats, or mitigates diseases or health conditions in humans.” It also says that Henderson did not conduct any studies to show his therapies could do what he claimed.
As part of the proposed settlement, the defendants were ordered to pay $3.31 million — the amount the clinics generated in sales from 2014 to 2017 — but the FTC said that penalty will be suspended once Henderson pays $525,000 to the agency.
The clinics charged from $9,500 to $15,000 for the first round of treatments, according to the complaint, with follow-up “boosters” costing patients $5,000 to $8,000.
Even regulators have indicated that because of limited resources and the proliferation of the clinics, they have to focus their efforts on the worst actors in the industry.
In May, for example, the Food and Drug Administration and the Justice Department moved to stop two clinics from providing stem cell treatments to patients, alleging that they were endangering patient safety. But the clinics — one in Florida and one in California — were by then widely known by critics of the industry. A 2015 procedure at the Florida clinic led to three women going legally blind, and the California clinic was involved in making an experimental cancer treatment from a smallpox vaccine that is not commercially available.
Biologists from Tufts University have fine-tuned an environment for 3D test tube “mini-brains” so that they can function like a living nervous system for months.
Test tube brains may sound like something out of a dystopian science fiction or horror movie, but scientists are using them to understand Alzheimer's disease, Parkinson's disease, and traumatic brain injuries, and even detect these conditions early.
Now, according to research published in the American Chemical Society’s Biomaterials Science & Engineering journal this month, these mini-brains can survive for at least nine months when grown in a mixture of protein from silk and stem cells from patients with diseases like Alzheimer's and Parkinson's. Artificial mini-brains typically have a short life span, but these long-lasting brains allow scientists to observe the progression of neurological diseases in groups of cells over time so that they can pin down the earliest signs of disease onset.
To be clear: the goal of these “mini-brains” isn’t to replace a human brain. Rather, the purpose of these mini-brains is to understand how the human brain works and figure out how to treat neurological diseases. Ethical quandaries always arise when testing medication on humans and animals. Meanwhile, mini-brains have the advantage of being alive and able to exhibit “spontaneous electrical activity,” but they’re not conscious in the way that a living brain is .
David L. Kaplan, a biomedical engineering professor at Tufts University, said in a press release that the fine-tuned test tube environments of these mini brains doesn’t just help the brain live longer; it also helps them support various types of brain cells. "The silk-collagen scaffolds provide the right environment to produce cells with the genetic signatures and electrical signaling found in native neuronal tissues,” Kaplan said. Basically, they're not just bundles of nerve cells, but different types of specialized cells that would be found in a real human brain.
Tufts has been working for more than five years to develop mini-brains optimized for neurological research. Back in 2013, this research team was able to mimic the brain of a nine-week-old fetus out of stem cells taken from human skin. Then, in 2014, they tried shocking and banging these mini-brains in order to study concussions and traumatic brain injuries.
Brains are not the only organ that scientists have grown from just a handful of stem cells. In fact, scientists have created a human retina in a dish, lab-grown testiclesand vaginas, blood vessels, and a living layer of human skin. But the purpose of these lab-grown organs would be to transplant them into a living body in order to treat or repair certain conditions or injuries. For instance, artificial testicles could be used to help people with genital injuries conceive biological children.
October 18, 2018, University of Rochester Medical Center
Researchers at the University of Rochester Medical Center (URMC) have discovered a potentially new approach to deliver therapeutics more effectively to the brain. The research could have implications for the treatment of a wide range of diseases, including Alzheimer's, Parkinson's, ALS, and brain cancer.
"Improving the delivery of drugs to the central nervous system is a considerable clinical challenge," said Maiken Nedergaard M.D., D.M.Sc., co-director of the University of Rochester Medical Center (URMC) Center for Translational Neuromedicine and lead author of the article which appears today in the journal JCI Insight. "The findings of this study demonstrate that the brain's waste removal system could be harnessed to transport drugs quickly and efficiently into the brain."
Many promising therapies for diseases of the central nervous system have failed in clinical trials because of the difficulty in getting enough of the drugs into the brain to be effective. This is because the brain maintains its own closed environment that is protected by a complex system of molecular gateways—called the blood-brain barrier—that tightly control what can enter and exit the brain.
A prominent example of this challenge is efforts to use antibodies to treat the buildup of amyloid beta plaques that accumulate in the brains of people with Alzheimer's. Because antibodies are typically administered intravenously, the entry of these large proteins into the brain is thwarted by the blood-brain barrier and, as a result, it is estimated that only two percent actually enter the organ.
The new research taps into the power of the glymphatic system, the brain's unique process of removing waste that was first discovered by Nedergaard in 2012. The system consists of a plumbing system that piggybacks on the brain's blood vessels and pumps cerebral spinal fluid (CSF) through the brain's tissue, flushing away waste. Nedergaard's lab has also shown that the glymphatic system works primarily while we sleep, could be a key player in diseases like Alzheimer's, and is disrupted after traumatic brain injury.
In the study, the researchers took advantage of the mechanics of the glymphatic system to deliver drugs deep into the brain. In the experiments, which were conducted on mice, the researchers administered antibodies directly into CSF. They then injected the animals with hypertonic saline, a treatment frequently used to reduce intracranial pressure on patients with traumatic brain injury.
The saline triggers an ion imbalance which pulls CSF out of the brain. When this occurs, new CSF delivered by the glymphatic system flows in to take its place, carrying the antibodies with it into brain tissue. The researchers developed a new imaging system by customizing a macroscope to non-invasively observe the proliferation of the antibodies into the brains of the animals.
The researchers believe that this method could be used to not only deliver into the brain large proteins such as antibodies, but also small molecule drugs and viruses used for gene therapies.
October 18, 2018 by Nina Bai, University of California, San Francisco
One day after head injury (left), bright dye along the edge of the brain suggests damage to the meninges, or the brain’s protective lining. After 35 days (right), the dye no longer appears, indicating the meninges may have healed. Credit: Larry Latour, PhD, National Institute of Neurological Disorders and Stroke
A bump to the head from slipping on the stairs, falling off a skateboard, or running into an open cupboard door has long been seen as a temporary injury, something resolved with a little rest.
But a growing body of research suggests that, for some people, even concussions that seem mild can have serious, long-lasting consequences, including an increased risk of Parkinson's disease and dementia.
In the United States, nearly three million people every year visit the emergency room for traumatic brain injuries, with 70 percent to 90 percent sustaining so-called mild traumatic brain injuries (mTBI), more commonly known as concussions. These numbers don't account for the many people who suffer concussions but do not seek medical attention.
Researchers at UC San Francisco are among the scientists working to understand how concussions cause long-term damage – and how they might be treated.
Uncovering Long-term Risk
The danger of more severe traumatic brain injuries sustained in war or professional sports is well documented, though they still lack effective treatments. The new revelations concern mild head injuries that can happen on the playground or your morning commute.
A concussion is generally defined as a change in normal brain function in response to an external force to the head, and does not necessarily include loss of consciousness.
In two recent large-scale studies of over 300,000 people, UCSF researchers found that even a single concussion was associated with an increased risk of Parkinson's disease and dementia.
The studies looked at military veterans with different levels of traumatic brain injury, including the types of concussions that are sustained every day in civilian life, said Kristine Yaffe, MD, professor of psychiatry, neurology and epidemiology, whose lab conducted the studies. Earlier studies in civilian populations identified similar long-term effects from concussions.
In fact, among traumatic brain injuries seen in emergency rooms, most are the result of car accidents, although in older adults, two-thirds are from ground-level falls.
Even head injuries that don't show up on a CT scan or MRI – and many do not – can increase the risk for future neurological problems.
Searching for the Missing Link
UCSF researchers Daniel Lim, MD, PhD, and Geoffrey Manley, MD, PhD, both members of the UCSF Weill Institute for Neurosciences, are working on a blood test that could spot brain injuries right after they happen. Credit: Noah Berger
Now that scientists know there is a connection between concussion and increased risk for neurological decline – the challenge is untangling what occurs in between.
Researchers suggest several possible mechanisms that could link concussion and mental decline. Perhaps the concussion triggers a cascade that increases abnormal protein buildup in the brain, a common hallmark of neurodegenerative diseases.
The concussion might cause inflammation or vascular changes. Another theory is that the injury could make the brain more vulnerable overall, what the researchers call a loss of brain reserve.
More likely it's a combination of different things in different people. "In my opinion, it's going to be proven to be multifactorial," said Raquel Gardner, MD, assistant professor of neurology, who was the lead author on the Parkinson's study.
But the time between an injury and future mental decline may be many years.
"Most people who get Parkinson's or dementia get it late in life, so the lag between having a TBI early in life and getting a neurodegenerative disease could be decades," said Gardner.
Following patients for extended periods of time can be difficult, and the alternative, having patients report their own concussion history and cognitive changes, can be unreliable.
One way that UCSF scientists are trying to capture the changes leading to a neurodegenerative disease is by studying people who sustain TBI in later life and in whom changes may occur on a shorter timeline. A new study is enrolling geriatric patients with a partner who can attest to changes in the patient's neurological symptoms before and after a concussion and rule our pre-existing neurological disorder.
Researchers are also making progress on how to diagnose concussions early and, the ultimate challenge, how to counter their damage.
A Better Way to Diagnose
One big first step is understanding exactly who has a concussion – which isn't as simple as screening for the presence of a virus or bacteria.
But UCSF researchers Daniel Lim, MD, Ph.D., and Geoffrey Manley, MD, Ph.D., are working on a blood test that could spot brain injuries right after they happen.
The two are focused on using long noncoding RNAs (lncRNAs) – molecules that are remarkably tissue-specific and can leak out of a cell when it is injured. Distinctive lncRNAs found in the blood can be traced to broken bones, torn muscle, or injury to organs like the heart and kidney. Likewise, brain-specific lncRNAs in the blood would indicate a brain injury.
"The brain is making a whole panel of lncRNAs that occur nowhere else in the body," said Lim. "We realized that such exquisite brain-specificity makes lncRNAs attractive as biomarkers for concussion."
Currently, head injuries that show up on a CT scan can be diagnosed by protein biomarkers such as GFAP and UCH-L1, but those may not be sensitive enough to pick up concussions, according to Lim. He hopes lncRNAs will offer a more sensitive biomarker for concussion, one that may be even specific enough to locate the injury to particular regions of the brain.
With funding from a Weill Innovation Award, the researchers have collected blood samples from dozens of patients who have sustained different degrees of brain injury. The researchers are analyzing the samples for lncRNAs and identifying which ones are the most specific and abundant after brain injury.
Ultimately, their work could lead to a portable blood test that could immediately diagnose a concussion, perhaps on the field at a child's football game.
Major Gap in Care
For now, the options for someone diagnosed with a concussion are limited.
Researchers say it's important to avoid a second concussion before the first one heals, because repeated concussions multiply the damage. Cognitive rehabilitation exercises, like specially designed video games, may also help boost brain reserve.
Follow-up care to treat symptoms such as headaches, dizziness, depression and anxiety can help prevent lasting disability, according to Manley, professor of neurosurgery. Manley is the principal investigator of the multicenter TRACK-TBI (Transforming Research Clinical Knowledge in Traumatic Brain Injury) study, the largest precision medicine study of TBI to date, which is tracking thousands of people nationwide who visit the emergency room for head trauma.
TRACK-TBI has found that less than half of patients who visit the emergency room for concussion received any follow-up within three months, including educational materials and doctor's visits.
"Many of those who aren't being seen are suffering and need medical attention," he said. "It's a major gap in care that represents an important public health issue in this country."
In the coming years, TRACK-TBI will attempt to answer some crucial questions, such as the value of blood-based biomarkers and advanced MRI imaging techniques in diagnosis and the role of genetics. It will also test new phase II drugs in clinical trials.
In Mice, Clues to a Cure
There are glimmers of hope that the harm from concussions can be reversed.
In mice that have sustained concussions, treatment with a molecule called ISRIB (which stands for Integrated Stress Response InhiBitor) was able to fully reverse cognitive damage. Even more surprising, the treatment was effective when given months after the injury, which could potentially translate to years after injury in humans, and the reversals appear to be permanent. These studies were also supported by a Weill Innovation Award.
"We were blown away," said Susanna Rosi, Ph.D., who co-led the ISRIB study with the discoverer of the molecule, Peter Walter, Ph.D. Her team repeated the experiment three times and also tested different animal models of concussion, just to make sure, and saw the same results.
"Despite what trauma does to the brain, it seems there are reserves, at least in the rodent brain, that we can use to make the brain function again," said Rosi, who directs neurocognitive research at the Brain and Spinal Injury Center. The stunning results in mice offer hope for reversing the effects of TBI in humans.
ISRIB works by resetting a normal biological reaction that can go awry in brain injury.
Under stress, cells activate a stress response, which shuts down the cells' production of proteins as a temporary protective mechanism. A traumatic brain injury can activate the stress response chronically in brain cells, impairing the brain's ability to form new memories. ISRIB removes the block and appears to restore normal brain function.
It's still unclear how the cellular stress response is involved in neurodegenerative disease, though it's known to increase with normal aging, says Rosi.
Despite the unanswered questions, like if the ISRIB treatment effects will translate to humans, researchers say they are generally optimistic about the future of concussion treatment.
"People don't understand what a new field this is," said Yaffe. Her research is among those that have brought public awareness to the dangers of concussions in just the last few years.
"We have to be extremely positive that we have so many tools and resources we didn't have five years ago," said Rosi, naming high-resolution imaging, single-cell sequencing, and more precise biomarkers as important advances.
And a silver lining: concussion research may yield insights into ways to fight Parkinson's and dementia. "Unlike any other risk factor we know for neurodegenerative disease, TBI has a specific time stamp," said Gardner. "It may be a unique opportunity to intervene at the earliest possible stage."
