Bionic handball: A daughter’s take on deep brain stimulation

BaskingInSun_640In 2013, Dennis and his family traveled from Missoula to Portland so he could undergo Deep Brain Stimulation surgery for his Parkinson’s disease.

We’ve shared Dennis’ Parkinson’s story and the perspective from his wife Mary Ellen, as the primary caregiver.

Now, their daughter Daphne gives us a peek at what it was like for their family the night before surgery.

Tuesday, August 6, 2013

Bionic Handball

When you or a loved one is suffering from a disease, every cure or beneficial procedure seems to be put into a context of percentages. This becomes particularly true when dealing with surgery. Right now, I am hanging on to 1 in 1000.

1 in 1000 is the chance of something going seriously wrong during tomorrow’s surgery. Pretty nice odds when the lifetime chances of getting seriously hurt in a motor vehicle accident are 1 in 266. Really, getting through Portland traffic to get to the hospital may be more statistically dangerous than having deep brain stimulation! (Other interesting percentages: getting hit by an asteroid is 1 in 500,000, getting cancer is 1 in 7.)

Tomorrow morning Den will go in to surgery, the second DBS patient of the morning. When I asked the doctor, “What about alcohol after surgery?”, he replied, “You want recommendations? Oregon has some nice Pinot.”  It was established that Den can have a nice glass of celebration wine when he gets out of ICU.

Den will leave ICU with two U shaped transmitters in his forehead. About 10 days later he will go back into surgery to implant the power pack into his chest. It will then be programmed and turned on mid-September. So, tomorrow is the first part of a month long journey to finding some relief from Parkinson’s: in short,  we won’t know if the surgery worked for him until the device is programmed and turned on about a month from now.

In the time between tomorrow’s surgery and the chest implant, Den will have to rest his brain. He was told not to think too much and to take life very easy:  his brain needs to rest and heal. All questions about economics or geographical trivia will have to be answered upon his return to Missoula. I thought he could watch the E! Entertainment channel as much as possible, particularly any reality show with Kardashian in the title. Mom and he will, instead, head for the coast for the recovery period where he can be by the sea, which is probably a better idea.

Tomorrow feels hopeful. His doctor is one of the best and so is this health center. Den  is having such a hard time with Parkinson’s that we feel grateful we have this procedure as a possible chance to resume a more normal life. Den spent a fair amount of time with the doctor today asking if the wire from his chest to his brain could be longer so he could have full motion during handball. It can’t, which could provide a good excuse if he loses a handball game after recovery. As Den showed the doctor the full motion he needed for handball, I felt a surge of happiness: it has been a long time since he has talked about playing his favorite sport.

Thank you all for your encouragement, support, and hope.

2016 update from Daphne:

I clearly remember this time in our lives: the night before the surgery, our family (my parents, four kids and husband) went out to a chic, bustling restaurant in Portland. We laughed and talked about everything but the surgery — just gave a lot of “thankfuls” for having each other and life as it was so far.

The feeling before such a major surgery is surreal: dream-like, almost, in its intensity and its possibility.  After the surgery, we were relieved everything went well and felt quite hopeful about Den having some relief from Parkinson’s symptoms.

While it was not a cure-all for him, life after the surgery has certainly been better for him than before it, and I do believe it has given him more years to participate in activities he enjoys. Since his Parkinson’s diagnosis almost 15 years ago, Den has fought to define the role of Parkinson’s in his life and not have it define him: I think the surgery has given him more years to feel he is in control of the disease.

For this, and for his daily presence of support, love, and good humor, I am forever grateful.   

Headers in soccer are a leading cause of concussion

11-year old blond girl playing with a  soccer ballAmerican Football may still be the leading concussion injury for all sports in the US, but soccer caused the second highest number of concussions in high school sports.

Soccer is also the number one cause of concussions for girls in high school sports.

Furthermore, women soccer players sustain about 1.7 times more concussions than male soccer players.

The cause of this is unknown, but may be related to the aggressive style of play in women’s soccer, resulting in more body and ground contact.

Overall, injury statistics tell us that 30% of all soccer-related concussions are from attempting to head the ball.

This is actually not because of the ball hitting the head, but rather the opponent’s head or body hitting the player’s head.

74.2% of boys’ concussions are from heading the ball.  It also causes 58.1% of girls’ concussions, plus a higher percentage in women due to player to ground contact.

Nevertheless, 40% of all concussions in soccer are due to arm or elbow to head contact and 60% of all heading related injuries are concussions.

Limiting the number of headers and or the contact associated with headers by enforcing current rules or making rule modifications may make a significant impact on the concussion rate.

Soccer is a great sport and our goal is to do anything we can to make it safer so we can encourage future participation.

Marar M. McIlvain N. Fields S. and Comstock R. Epidemiology of Concussions Among United States High School Athletes in 20 Sports. Am J Sports Med. January 2012.

Jim Chesnutt


Jim Chesnutt, M.D. is the director of the OHSU concussion program, serves as Co-Director of the Oregon Concussion Awareness and Management Program, Medical Advisor to the Oregon School Activities Association (OSAA), and is a member of the Governor’s Task Force on Traumatic Brain Injury.

Living with a husband who has Parkinson’s disease

Dennis was diagnosed with Parkinson’s 15 years ago and underwent Deep Brain Stimulation at OHSU in 2013. Last week, we heard his story, from the patient perspective. Here, his wife Mary Ellen provides a look into the caregiver’s frame of mind.

Originally published on Summit For Parkinson’s, a group of Montanans giving back to the Parkinson’s community.

Screen Shot 2016-03-25 at 10.01.20 AMThe caregiver’s perspective

“How’s Dennis?” That is the typical question of friends and acquaintances wanting to show they care about the health of my husband. “Up and down,” I usually reply. But I am really thinking, “I wish I knew.”

It’s difficult to know how anyone is who has Parkinson’s. The days are not predictable. My husband and I  have lived with his Parkinson’s for ten years. He has what the experts term, “idiopathic Parkinson’s,” which, translated, appears to mean “Dennis appears to have Parkinson’s, but it’s just not typical.”

So given that Dennis has “idiopathic Parkinson’s,” I don’t know if what I am experiencing with his Parkinson’s is typical or not. That said, I do believe caregivers share a great deal in common no matter what the formal diagnosis of the partner may be.

Living with a Husband Who Has Parkinson’s

For the most part, living with Parkinson’s is like having a third person with you at all times. Imagine having someone with you who takes control randomly and changes his mind at will.  It’s stressful. The major issue I have found living with Parkinson’s is its unpredictability.

In terms of our lives, I am most challenged by my inability to plan.  I never know how Parkinson’s will impact my husband. Dennis can be doing something fairly normal, such as having dinner or watching television. Then, suddenly, he can’t walk. Sometimes his is even frozen in place. He can be ready to go to a football game one minute and unable to get out of the car the next. He can enter a party with enthusiasm looking energetic and lively and find that he has to leave the festivities a half hour later hardly able to navigate out the door. Our lives have become a “best guess” scenario in terms of how Dennis’ body will perform at any given time.

This unpredictability is often misunderstood by people who don’t know Parkinson’s symptoms or appreciate the complexity of the disease. I understand their confusion and sometimes disbelief. It is difficult to accept that a person with Parkinson’s who looks healthy enough one when he entered the room lacks the control to “buck-up,” “push through” or “hold on a minute.”

What Parkinson’s has Taught me

COMMUNICATION IS ESSENTIAL: In spite of the issues that often make living with Parkinson’s a nightmare for Dennis and for me, he and I daily talk about his feelings and mine. Because of this, we constantly make a point of communicating straight up. We don’t hide our feelings and opinions from each other. I don’t tell other people about what it’s like living with the disease that I don’t tell him directly. He doesn’t try to cover up his disappointment in what he can and can’t do. Because we communicate, we are able to laugh a lot about things such as breaking glasses or slopping food or typing on a computer. Laughter helps us both deal with frustration and anger and fear.

Styling at the Glastonbury Opera U.K. 2010.

Styling at the Glastonbury Opera U.K. 2010.

FLEXIBILITY IS A GIVEN: There is nothing that a person has planned that can’t be postponed or changed. Nothing.

PATIENCE IS MANDATORY: It’s a lot easier for a healthy person to do things for a person with physical challenges than to wait while they do it for themselves. I am healthy. I could play the role of superwoman. I don’t. I encourage Dennis do as much as he can for himself. If it takes him three hours to sweep the walk, so be it. If he needs salt, he gets up and gets it. Dennis has always taken pride in contributing to the well-being of our household. He deserves to participate. It is my belief that if I take over all the responsibilities for running our lives, I will eventually make him weaker and more dependent. This is not a good situation for either of us.

So, our “deal” is that when he is in dire need or is completely and totally frustrated and he needs my help, he tells me. I would call on him if I were experiencing the same thing. Otherwise, he takes care of things himself at his own pace which is on his Parkinson’s clock.

I find that when we are with friends or even just out in public, people are often so concerned that they jump up to help him. Some strangers have even grabbed his arm on occasion. When I see Dennis is in need, I just tell myself, “I must have patience.” Dennis deserves the right to be in control of his situation. I don’t intervene unless he requests it, or after I’ve consulted with him first. I notice I have begun treating all people with disabilities more patiently than I ever had before we began living with Parkinson’s. Now, when I see someone struggling to do something, I don’t just insist on helping. I ask. I wait. I am patient. It’s hard.

Meet Dennis: Husband, educator, Parkinson’s patient

In 2013, Dennis and his family traveled from Missoula to Portland so he could undergo Deep Brain Stimulation surgery for his Parkinson’s disease.

In honor of Parkinson’s Awareness Month, Dennis has agreed to share his Parkinson’s story.

Originally published on Summit For Parkinson’s, a group of Montanans giving back to the Parkinson’s community.

Screen Shot 2016-03-25 at 9.42.04 AMMy intimate experience with Parkinson’s disease began 20 years ago when my father, at age 74, was diagnosed and began his journey dealing with the progress of the disease.

I watched him decline from a six-foot four healthy senior citizen and former police officer to a man who was unable to walk without aids, was unable to care for his spouse without endangering himself.

Dad finally passed away due to the consequences of two broken hips from Parkinson’s related instability leading to treacherous falling incidents.

The complications associated with pain management and other medical issues along with having Parkinson’s overwhelmed him. He passed away 10 years ago at age 84. I was diagnosed with Parkinson’s within a month of his death at age 54. I would have been very happy to wait another 20 years to age 74, but such choices are not available.

My Parkinson’s developed almost exactly in the same progression as my Dad’s giving some credence to the genetic causality argument. At this point my wife and my family including the ever developing little support unit now totaling four grandchildren have supported me and cared for me in ways that make one certain that a diet of love and a lot of laughter and commitment to each other is essential when facing any progressive disease or for that matter any health problem.

It may have been due to my observation of my father’s physical decline but I became committed to fighting Parkinson’s by following a program of vigorous exercise. Exercise is given considerable attention through the literature, websites and to some extent by the various neurologists I consulted at the beginning of this journey. However it is not given enough emphasis compared to the medicinal approaches. The key to exercise in a realistic world depends on one’s own individual commitment and to the support and accommodation by others.

In my case, I continued to play handball, golf, bicycle, ski, swim, and dry fly fish when my condition allows. All of the debilitating aspects of Parkinson’s such as loss of agility and hand eye coordination, balance and body management and control in three dimensional environments can be managed somewhat and even pushed back by engaging in this variety of athletic activities.

Fishing in Alaska with my son, 2010

Fishing in Alaska with my son, 2010

I owe the deepest gratitude to those men in the Missoula handball community for their unwavering encouragement and demanding standards “that the game must be played right” for 10 years of hard exercise in the company of good hearted men that kept me going when lesser incentives might let one quit trying to go it alone.

In addition, those I have played golf with, swum with, bicycled with, skied with and fished with kept me on track as well. In such an active environment I lost 50 pounds and maintained a number of skills after 10 years.

I cannot explain how or why the exercise works as I can’t explain how I can wobble my way to the tee box and hit a solid drive or seven iron between tremors, or cast to a rising cutthroat between shakes, but it works. I’m sure it works because I have continuously maintained my exercise program. Those skills make everyday life manageable within the parameters set by the progression of the disease.

The medicinal choices available to those people afflicted with Parkinson’s are limited with no major breakthrough cure emerging at this time. Further research is essential and needs the support of massive financial and intellectual resources. Until the time a cure is found those with Parkinson’s must live well today and must be ready for tomorrow and that requires more than medications alone.

When I was diagnosed with Parkinson’s I was a Professor of Economics and Asian Studies at the University of Montana. Teaching was my passion and my career was on full overdrive with fascinating work in emergent China with the US State Department and the Foreign Ministry of China just getting underway. I also served as an expert witness Economist in civil and criminal litigation for 30 years at the national level, including working for the US Department of Justice.

At the end of my first four years with Parkinson’s I had to stop teaching on a regularly scheduled basis primarily due to the inability to manage the side effects of medication. I couldn’t teach without unduly distracting my students. To a person, the undergraduate and graduate students at the University of Montana gave me the most inspiring level of support and genuine accommodation anyone could ever hope for. I have nothing but respect for them and hope for the future based on their good hearts and souls.

Because of the progress of the disease, it became extremely difficult to travel internationally. The research and program development work in Asian Studies and Economics came to an end in the seventh year.  I received tremendous support and encouragement from a broad range of faculty colleagues who were colleagues in the broadest and noblest sense of the term.

I was able to keep my expert witness work viable by narrowing its scope progressively until the end of the 10th year. Expert testimony requires an extraordinary amount energy that must be sustained to maintain analytic rigor in changing markets and to prepare for depositions and court room testimony. Eventually Parkinson’s makes testifying in front of judges and juries for long periods of time physically impossible.

I emphasize the continuation of work during the development of Parkinson’s to ensure those who eventually face the same problem that they can effectively continue working as long as they are very careful to be highly realistic regarding their changing capacity. In my case, the extraordinary professionalism of lawyers, judges and particularly the amazing capacity of jurors to look past disability and find the value of solid analysis can never be underestimated. It is a tribute to the way our system of justice really works.

The story of my Parkinson’s journey has many more chapters to be written. However, the story so far is mostly about the importance of your mate, your family, your friends and colleagues plus the goodwill of fine decent people that appear out of thin air, most of whom you know for only moments, who graciously support your will to fight on. Because of their support a person must find the will to fight on.

Get back in the game with ImPACT concussion testing

Having worked in the high school setting as an athletic trainer for eight years before coming to the OHSU Sports Medicine department, I have found that concussion management is one of the most complex tasks for a high school athletic trainer to facilitate.

Between the on-the-field examination to determine if the athlete has a concussion, educating the coaching staff and parents on concussion management, following up with the school administration and staff regarding accommodations for the concussed athlete, and managing the athlete through the return-to-play process in collaboration with the team physician, an athletic trainer can find themselves very busy.Players on the field

One useful tool that assists with the return-to-play decision making process is the ImPACT concussion evaluation system.

This computer-based neurocognitive-testing program allows an athletic trainer and team physician to make a more objective return-to-play decision based on data specific to the concussed athlete.

To effectively utilize the ImPACT test, it is important that at the beginning of the playing season, each student athlete takes the baseline ImPACT test. The baseline test represents the athlete’s attention span, working memory, sustained and selective attention time, response variability, non-verbal problem solving, and reaction time.

If the athlete sustains a concussion during the playing season, the athletic trainer will conduct a physical exam of the athlete, a post-injury ImPACT test, and follow a graded return-to-play program before allowing the athlete to return to full competition. The post-injury ImPACT test reevaluates the same categories as the baseline, thus providing an objective measurement of the changes the athlete may be experiencing after the concussion.

The return-to-play process also includes being evaluated and cleared by the team physician or the athlete’s primary care provider.

The ImPACT test is a very useful tool to have in the toolbox to assess return to play readiness, but it is important to remember that it is just a tool that is most effective when combined with the physical exam and graded return-to-play process.

If you, or someone you know is interested in completing a baseline ImPACT test please contact the OHSU Sports Medicine clinic at 503-494-9992 with any questions or to set up an appointment. We offer baseline ImPACT testing and post concussive management by our Sports Medicine specialists as well as many other services and we look forward to serving you!


Ryan Rockwood, A.T.C. specializes in high school outreach, presents to local schools and businesses on concussion management, and is a member of the concussion management team at OHSU Sports Medicine.  


Research links infrequent daily computer use and common early signs of Alzheimer’s disease

A new study sheds light on a powerful tool that may detect signs of Alzheimer’s disease before patients show any symptoms of cognitive decline: the home computer.  

OHSU researchers have found a significant correlation between infrequent daily computer use and brain imaging signs commonly seen in early-stage Alzheimer’s patients. The researchers have been following a group of volunteers in Portland for nine years through a suite of embedded technology in their homes.Senior at computer

These tools allow the researchers to assess their mobility, sleep, socialization, computer use and medication intake. 

The purpose of this monitoring is to identify meaningful changes in everyday life that don’t involve the participants taking tests or going to doctor appointments.

Using an MRI scan, the researchers measured the volume of the hippocampus — a brain region integral to memory function — in adults aged 65 years and older who were cognitively intact and dementia-free.  

Diminished hippocampal volume is a well-known sign, or biomarker, of Alzheimer’s disease and the eventual development of dementia. 

The study, led by Lisa Silbert, M.D., with the OHSU Layton Center for Aging & Alzheimer’s Disease, found that an additional hour of computer use a day was associated with a .025 percent larger hippocampal volume. A smaller hippocampal volume is an indicator of increased risk for developing Alzheimer’s disease.

Silbert and colleagues hypothesize that the reason that patients with smaller hippocampal volumes may spend less time using their home computer is it requires the use of multiple cognitive domains, including executive function, attention and memory. 

The researchers will continue to follow these participants to see if their smaller hippocampal volume and decreased computer use predict future cognitive decline.

Learn more:
Journal of Alzheimer’s DiseaseLess daily computer use is related to smaller hippocampal volumes in cognitively intact elderly
The OregonianCould computer use keep Alzheimer’s at bay?
Portland Business Journal: Home computer use could help predict Alzheimer’s risk
Neuroscience News: Infrequent computer use may be an indicator of early cognitive decline

Men suffering from depression who have social support less likely to seek mental health treatment

Researchers, led by Alan Teo, M.D., assistant professor of psychiatry at OHSU, and researcher at the VA Portland Health Care System, sought to determine whether support from a loved one encourages people experiencing depression to seek treatment from a health provider or whether that support, by serving as informal treatment, inadvertently discourages people from seeking mental health services.Closeup of a thoughtful young man seen through a window

Their findings show that men experiencing moderate or severe depression who had social support from family or friends were likely to see a primary care or other non-mental health care providers, but only rarely saw a mental health specialist.

The less social support that men reported, the more likely they were to seek help from a mental health provider.

Women, on the other hand, were relatively consistent in their use of mental health services. The researchers studied a nationally representative sample of more than 1,000 middle-aged and older adults in the United States.

Social support can take the form of emotional (someone serving as a confidant), informational (a friend providing facts on depression) or instrumental (a family member driving someone to an appointment) help.

Dr. Alan Teo

Dr. Alan Teo

Depression is the leading cause of disability and a significant risk factor for suicide.

Fewer than half of severely depressed people receive drug or behavioral treatment.

Just one in 10 with persistent depression receive both appropriate medication and counseling, and older adults with depression are especially unlikely to use mental health services.

The study authors hope to raise awareness among general practitioners that they’re likely to encounter men with clinical depression who are unlikely to seek mental health treatment themselves. The researchers encourage proactive treatment with an antidepressant, psychotherapy, or collaboration with mental health providers.

The paper was published in the journal General Hospital Psychiatry.

Diabetes drug may prevent recurring strokes and heart attacks

Wayne Clark, M.D.

The OHSU Stroke Center was an integral part of an NIH-funded global study that has shown that a diabetes drug may prevent a second stroke or heart attack in patients with insulin resistance.

The study was conducted at 167 institutions in seven countries, with the Oregon Stroke Center enrolling the second highest number of participants across the globe.

Wayne Clark, M.D. was a co-author of the paper.

The following press release was originally published by the NIH on February 17, 2016:

NIH-funded global study suggests novel approach for preventing repeated cardiovascular events

Pioglitazone, a drug used for type 2 diabetes, may prevent recurrent stroke and heart attacks in people with insulin resistance but without diabetes.

The results of the Insulin Resistance Intervention after Stroke (IRIS) trial, presented at the International Stroke Conference 2016 in Los Angeles and published in the New England Journal of Medicine, suggest a potential new method to prevent stroke 20160217-ischemic-strokeand heart attack in high-risk patients who have already had one stroke or transient ischemic attack.

This large, international study was supported by the National Institutes of Health’s National Institute of Neurological Disorders and Stroke (NINDS).

The IRIS trial is the first study to provide evidence that a drug targeting cell metabolism may prevent secondary strokes and heart attacks even before diabetes develops.

Insulin regulates metabolism and keeps blood sugar levels from getting too high, along with many other processes, in the body. Insulin resistance is a condition in which the body produces insulin but does not use it effectively.

“This study represents a novel approach to prevent recurrent vascular events by reversing a specific metabolic abnormality thought to increase the risk for future heart attack or stroke,” said Walter J. Koroshetz, M.D., director of the NINDS.

Read more…

Discover how alcohol, gaming, and marijuana impact your brain

Indulging in pleasurable activities is sometimes characterized as a dichotomy of good or bad. But is it all or nothing when it comes to the brain? When are healthy pleasures susceptible to harmful effects?

Our 2016 Brain Awareness Season will delve into the brain science behind three very popular pastimes: alcohol, gaming, and marijuana.

Held at the Newmark Theater in downtown Portland (sometimes called “Brains on Broadway”), this series features nationally known neuroscience experts and authors.


Alcohol and the brain
Monday, February 22
7–8:30 p.m.

grant-head-banner600x600The positive health benefits of red wine have been popular news headlines for many years. In moderation, alcohol has been seen to improve cardiovascular health, immune system response, and even prevent gallstones.

On the other hand, the negative health and social impacts of alcoholism are apparent in just as much news coverage. Dr. Kathleen Grant will explore how behavioral neuroscience informs how, why, and when the risks of alcohol may outweigh the benefits.

Buy your tickets now

Gaming and the brain
Monday, February 29
7–8:30 p.m.

gazzaley-head-banner600x600The generation just coming of age has been exposed to more electronic technology than any one prior to it. Video games in particular have drawn scrutiny as influencing the obesity epidemic, attention deficits, and pronounced violence of our youth.

They also show promise as educational tools, memory enhancers, and improving high-level thinking. Dr. Adam Gazzaley will present the science behind your brain on games.

Buy your tickets now

Marijuana and the brain
Monday, March 7
7–8:30 p.m.

stella-head-banner600x600Oregon recently joined only three other states to legalize recreational marijuana. As consumption of the plant’s products becomes more a mainstream activity, its health benefits and risks will be at the forefront of policy discussions.

Dr. Nephi Stella will explain the role marijuana plays in cutting edge neuroscience research.

Buy your tickets now


The Season also includes the always popular Brain Fair and Teacher Workshop. Don’t miss these free opportunities to learn about the brain.

OHSU Brain Institute Brain Fair
Saturday, March 12, 2016
10 a.m.–5 p.m.brain-fair-03-1200x628

The OHSU Brain Fair is an annual event at the Oregon Museum of Science & Industry (OMSI). The Brain Fair is held each spring.

This year’s Brain Fair includes interactive exhibits, real human and animal brains, prizes and dozens of OHSU Brain Institute neuroscientists explaining and demonstrating their groundbreaking research in a way that will be fascinating for all ages.

No museum admission is required to attend.

Brain Awareness Teacher Workshop
Saturday, April 16, 2016

Let a teacher in your life know about this  special day for classroom teachers featuring presentations on the adolescent brain and early-life nutrition and a highly interactive resource fair.

Speakers include Bonnie Nagel, Ph.D. and Susan Bagby. M.D. who will touch on how addiction manifests itself  in the brains of youth, among other telling research.

Register now

Special delivery: Discovery of viral receptor bodes better gene therapy

There is much hope for gene therapy’s future potential to treat a number of human diseases. The use of adeno-associated virus (AAV) vectors to transport genetic material into cells has been critical to the initial success of experimental gene therapy treatments of hereditary diseases, including hemophilia B.  But in order to develop gene therapy cures for additional diseases and conditions, like diabetes and heart disease, it will be necessary to deliver the treatment to specific tissues. Achieving this required an understanding of how AAV enters cells. 


Michael Chapman, Ph.D.

Now, for the first time, researchers at OHSU and Stanford have identified the protein (KIAA0319L) to which AAV adheres on the outside of human cells and uses to gain entry, a discovery published in the journal Nature

The paper, “An essential receptor for adeno-associated virus infection,” is jointly authored by Michael Chapman, Ph.D., R.T. Jones Professor of Structural Biology, OHSU School of Medicine, and Jan Carette, Ph.D., Assistant Professor, Microbiology & Immunology, Stanford University School of MedicineMajor contributors to the study include Sirika Pillay, Ph.D., Stanford University School of Medicine, and Nancy Meyer, M.S., Research Associate, OHSU.  

The following post about the study originally appeared on Stanford Medicine’s blog, Scope.

Special delivery: Discovery of viral receptor bodes better gene therapy
Written by Bruce Goldman
Photo by Loco Steve

Photo by Loco Steve

Gene therapy, whereby a patient’s disorder is treated by inserting a new gene, replacing a defective one, or disabling a harmful one, suffered a setback in 1999, when Jesse Gelsinger, an 18-year-old with a genetic liver disease, died from immense inflammatory complications four days after receiving gene therapy for his condition during a clinical trial. It was quite a while before clinical trials in gene therapy resumed.

But what Stanford virologist Jan Carette, PhD, describes as “intense interest” in the field is once again in full bloom. Gene therapies for several inherited genetic disorders have been approved in Europe, and a gene-therapy approach for countering congenital blindness is close to approval in the United States.

That a virologist would be paying such close attention to this topic isn’t odd, as the most well-worked-out method for introducing genetic material to human cells involves the use of a domesticated virus.

If there’s one thing viruses are really good at, it’s infecting cells. Another viral trick is transferring their genes into cellular DNA — it’s part of their modus operandi: hijacking cells’ replicative machinery and diverting it to production of numerous copies of themselves. Scientists have become increasingly adept at taming viruses, tweaking them so they retain their ability to infect cells and insert genes, but no longer contain factors that wreck tissues or taunt the infected victim’s immune system into a rage destructive to virus and victim alike.

Adenovirus-associated virus — ubiquitous in people and not associated with any disease – makes a great workhorse. Properly bioengineered, it can infect all kinds of cells without replicating itself inside of them or triggering much of an immune response, instead obediently depositing medically relevant genes into the infected cells to repair a patient’s defective metabolic, enzymatic, or synthetic pathways.

Figuring out how to tailor this viral servant so it will invade cells more efficiently, or invade some kinds of cells and tissues but not others, would broaden gene therapy’s utility and appeal. In a series of experiments described in a study in Nature, Carette’s group, with collaborators from Oregon Health & Science University and the Netherlands, used a sophisticated method pioneered by Carette to bring that capability a step closer.

A virus can attach itself to a target cell by latching onto a molecule embedded in that cell’s surface. In the case of adenovirus-associated virus, that viral-receptor molecule is already known. (The molecule obviously is there for some constructive purpose, which doesn’t stop the invading virus from taking advantage of the mutual attraction.) Simply glomming on to the cell’s surface isn’t enough, though. To get to the all-important nucleus, where the genetic jewelry is ensconced, the virus has to penetrate the cell as well. Until now, the molecule on which adenovirus-associated virus hops a ride downtown was anybody’s guess.

In the new study, Carette and his colleagues identified, in human cells, precisely that transport molecule. This discovery could lead to ways of raising or lowering the molecule’s expression in different tissues so that therapeutic genes get delivered to their intended addresses, and nowhere else.


Read more:
Portland Business Journal: OHSU researchers reach major gene therapy breakthrough
MedCity News: Researchers in Oregon are changing the face of gene therapy with new breakthrough

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