Showing posts with label cognitive function. Show all posts
Showing posts with label cognitive function. Show all posts
Tuesday, November 27, 2012
Down syndrome and sleep
The Down Syndrome Research Group at the University of Arizona conducts research to further our understanding and treatment of the cognitive dysfunction associated with Down syndrome.
Part of our research studies sleep, which is very important for learning. Sleep can be a problem for people with Down syndrome. Our laboratory is one of the few places in the world that studies sleep in people with Down syndrome.
One of our studies may determine how obstructive sleep apnea affects learning and behavior in people with Down syndrome. We anticipate illuminating links between sleep and cognitive deficits, thereby enhancing the possibilities for treating sleep disruption.
Our study has also had an impact on the public's awareness that people with Down syndrome may have problems sleeping. We offered a family in Phoenix an opportunity for their son to take part in the sleep study. As a result, he is now receiving treatment that has changed his life.
His mother, Leticia Avena, wrote about the impact of the study on her son's life:
"As a little boy, Isaiah would snore loudly and he always seemed tired and grumpy. His ENT suggested removing his tonsils and adenoids. After the surgery, we noticed some improvement with the snoring and breathing, but he was still tired and irritable."
After we tested Isaiah's sleep patterns with a method of monitoring the quantity and quality of sleep called polysomnography, we recommended that the Avena family follow up with his pediatrician and have a formal sleep study done.
"Isaiah was diagnosed with sleep apnea and prescribed a continuous positive airway pressure (cPAP) machine. Who would have thought that a little machine like that could make such a big difference!" his mother wrote.
"He no longer snores, he's happier and more alert, and we've been able to cut back on his medication for ADHD. We are very grateful to the DSRG. They have made a big difference in Isaiah's life, which has made our lives better, too."
The Down Syndrome Research Group also provides opportunities for people with Down syndrome to intern in our lab.
Sherine Rocha, a 20-year old woman with Down syndrome, is one of our interns. Her volunteer work helps support several research studies already under way in the lab, including one that develops tools to assess people's cognitive abilities. These tools will be used in studies to tell if a therapy has worked. Sherine and her family were excited to hear that possible treatments are being tested right now.
Success stories like these inspire us. In December 2011, the Down Syndrome Research Group and the UA College of Science established DSA CARES (Down Syndrome Arizona! - Clinical Care, Advocacy, Research and Education) to continue our research and to develop partnerships with the community.
Sherine and Isaiah are just two of the individuals with Down syndrome who have already participated and benefited from DSA CARES. This partnership is critical for obtaining the resources needed to support Arizonans with Down syndrome for years to come.
Our ultimate goal is helping everyone with Down syndrome maximize their potential.
About the scientists
Lynn Nadel is a University of Arizona Regents' Professor of psychology and a faculty member in the Cognitive Science Program. He is an expert in the functioning of the hippocampus, a part of the brain involved in memory that is the major target of neurological interventions in Down syndrome.
Jamie Edgin is a University of Arizona assistant professor of psychology and affiliated faculty of the Sonoran University Center for Excellence in Developmental Disabilities. She studies memory in typical development and in neurodevelopmental disorders such as Down syndrome.
Experience Science
• UA Down Syndrome Research Group: dsrg.arizona.edu
• Arizona Public Media story on sleep in Down syndrome: https://www.azpm.org/p/top-health/2011/6/27/1830-sleep-and-down-syndrome
• KJZZ radio interview: archive.kjzz.org/news/arizona /archives/201009 /Down_Testing
How to participate
To take part in these studies, contact Jamie Edgin at 520-626-0244 or jedgin@email.arizona.edu
Tuesday, July 17, 2012
Friday, March 16, 2012
Down Syndrome Research and Treatment Foundation's plus15 campaign
I'm writing from the plus15 campaign, which is the Down Syndrome Research and Treatment Foundation's campaign to spread the word about Down syndrome cognition research. DSRTF supports research to improve learning, memory, and speech in people with Down syndrome, with the goal of greater independence and increased cognitive ability for our loved ones.
We're excited about World Down Syndrome Day and have planned a few ways to celebrate. We wanted to reach out and let you know, in the hope that you might share our excitement and pass the word along to your community.
Here's what we have going on:
- 3-to-1 donation matching on 3/21. Give to DSRTF on 3/21, and your donation will be matched 3:1, thanks to the generous support of one of our funders. This is an incredible one-day opportunity to maximize your donation to DSRTF. Please mark your calendars and give! $15 becomes $60, $25 becomes $100, and every bit counts. You can donate here: http://www.dsrtf.org/donate
- Webinar. In honor of World Down Syndrome Day, DSRTF is hosting a special webinar with Dr. Roger Reeves of Johns Hopkins University. As you may know, Dr. Reeves is a leading researcher in the area of Down syndrome, having studied it for over 25 years. DSRTF is a proud supporter of Dr. Reeves’ work, and we hope you will join us for this one-hour webinar about Down syndrome cognition research on Wednesday, March 21 at 10:00 AM PT/1:00 PM ET. Sign up here: http://plus15.webex.com/mw0306ld/mywebex/default.do?siteurl=plus15
- plus15's World Map. What would an increase in cognitive ability mean to you and your loved one with Down syndrome? plus15 is creating a world map — available here: http://www.dsrtf.org/plus15/3-21map — with testimonies, photos and videos to show the world, and our legislators, the importance of cognition research in providing greater opportunity to those with DS. To participate, send your first name, city/state, a video or a photo, and a note that completes the following sentence: "A 15 percent increase in cognition means that my (son/daughter, etc.) could _____________." Upload to our Facebook page at http://www.facebook.com/plus15 or send it via e-mail to julie@dsrtf.org. Together we'll put Down syndrome on the map.
Grassroots support is essential to efforts like ours, and we count on word of mouth — or in this case, word of blog — to help spread the word about what we do.
Friday, January 13, 2012
Patients with Down Syndrome Not Benefitted by Alzheimer's Drug
from Third Age:
Patients with both Down syndrome and Alzheimer’s disease are not benefitted by a popular drug used to treat cognitive decline, a new study shows. According to HealthDay News, researchers from King’s College London found that the brain function of people older than 40 years with Down syndrome was not helped by taking memantine.
The results came as disappointing to researchers, who had been excited about the positive results found in mice with Down syndrome.
To test the effectiveness of memantine, 88 people with Down syndrome received the drug for one year, while another 85 people received a placebo. Some study participants had Alzheimer’s while some did not.
Overall brain function declined in both groups regardless of whether or not they were taking the drug.
In fact, memantine was not only ineffective, it was dangerous. Eleven percent of people in the group that took the medication experienced serious adverse side effects, compared to just seven percent of people in the placebo group. Five people from the memantine group eventually died of these complications.
Still, researchers were pleased that their work would contribute to the ongoing field of study involving Down syndrome and Alzheimer’s. According to HealthDay, the issue is particularly important as nearly 40 percent of people with Down syndrome will be diagnosed with dementia once they pass the age of 60.
“Memantine is not an effective treatment in this group of patients,” said study author Clive Ballard. “We believe that this robust finding will have implications for clinical practice and research strategy in the future. Specifically, therapies that are beneficial for people with Alzheimer’s disease are not necessarily effective for the treatment of cognitive impairment or dementia in the context of Down syndrome.”
The results came as disappointing to researchers, who had been excited about the positive results found in mice with Down syndrome.
To test the effectiveness of memantine, 88 people with Down syndrome received the drug for one year, while another 85 people received a placebo. Some study participants had Alzheimer’s while some did not.
Overall brain function declined in both groups regardless of whether or not they were taking the drug.
In fact, memantine was not only ineffective, it was dangerous. Eleven percent of people in the group that took the medication experienced serious adverse side effects, compared to just seven percent of people in the placebo group. Five people from the memantine group eventually died of these complications.
Still, researchers were pleased that their work would contribute to the ongoing field of study involving Down syndrome and Alzheimer’s. According to HealthDay, the issue is particularly important as nearly 40 percent of people with Down syndrome will be diagnosed with dementia once they pass the age of 60.
“Memantine is not an effective treatment in this group of patients,” said study author Clive Ballard. “We believe that this robust finding will have implications for clinical practice and research strategy in the future. Specifically, therapies that are beneficial for people with Alzheimer’s disease are not necessarily effective for the treatment of cognitive impairment or dementia in the context of Down syndrome.”
Wednesday, December 7, 2011
Neuron Finding Lifts Hopes for Down Syndrome Drug
from Psychiatric News:
Down syndrome is usually due to each cell in the human body having three copies, rather than two copies, of chromosome 21. This heartbreaking illness leads not just to a spate of physical abnormalities and cognitive dysfunction, but often to early-onset Alzheimer’s disease.
A pivotal brain region affected by Down syndrome is the hippocampus. Now scientists at Stanford University School of Medicine have made two important findings about what occurs in that region in a mouse model of Down syndrome, which purportedly translates to people with the syndrome.
One is a loss of two types of neurotransmitter-producing neurons in the hippocampus—acetylcholine-producing neurons and norepinephrine-producing neurons. The other is that this loss is linked with the overexpression of the amyloid precursor protein gene in the hippo-campus. Mutations in this gene, which is located on chromosome 21, are known to lead to early-onset Alzheimer’s, and it may be that early onset of Alzheimer’s pathology in people with Down syndrome is due in part to overexpression of the amyloid precursor protein gene.
These findings have provocative therapeutic implications for people with Down syndrome, the scientists also pointed out online September 27 in Biological Psychiatry. For instance, although the amyloid precursor protein gene should be a primary therapeutic target in Down syndrome, there are no safe and effective medications on the market to reduce the gene’s expression. In contrast, since a paucity of norepinephrine-producing neurons in the hippo-campus also seems to contribute to Down syndrome, medications that enhance norepinephrine levels in the brain and are already on the market to treat attention-deficit/hyperactivity disorder might be of therapeutic benefit to individuals with Down syndrome.
Moreover, such medications might also subdue the action of the amyloid precursor protein gene in such individuals, they speculated.
“We are indeed working on this group of drugs—drugs that are able to increase norepinephrine levels and that have already been approved by the Food and Drug Administration—in our mouse models,” Ahmad Salehi, M.D., Ph.D., a clinical associate professor of psychiatry at Stanford and the study’s senior investigator, told Psychiatric News. “This strategy could speed up the development of a treatment for cognitive function in Down syndrome enormously.”
The scientists’ discovery of a paucity of acetylcholine-producing neurons in the hippocampus of an animal model of Down syndrome holds therapeutic promise, the researchers noted. In fact, other researchers reported eight years ago that the Alzheimer’s drug donepezil, which slows the break down of acetylcholine in the brain, might improve cognitive scores and expressive language in children and adults with Down syndrome.
Yet if donepezil improves cognitive function and language in these individuals, is there reason to believe that medications that increase norepinephrine would be superior to donepezil in that regard? Asalehi believes there is. “I think using norepinephrine-ergic drugs would be far superior to cholinergic ones for the following reasons: The norepinephrine system has some regulatory effects on the cholinergic one. It has been shown that lesions in the former lead to increased severity of cholinergic deficits; most adults with Down syndrome will show Alzheimer’s-related pathology, particularly amyloid plaques. There are new studies showing that increasing norepinephrine levels in mouse models of Alzheimer’s significantly reduce amyloid accumulation. These findings suggest that using norepinephrine-ergic drugs might not only restore cognition in kids with Down syndrome, but also reduce Alzheimer’s-related pathology in adults with the syndrome.”
“Studies such as this one help to further our overall understanding of central nervous system function and in particular differences seen in individuals with Down syndrome,” Melanie Manning, M.D., director of the Center for Down Syndrome at Stanford’s Lucile Packard Children’s Hospital, told Psychiatric News.
“Many of the families of individuals with Down syndrome follow results from research studies such as this one with great interest. They express a desire to learn more about potential clinical applications that lie ahead.”
The research was funded by the Mental Illness Research, Education, and Clinical Center Department of Veterans Affairs; Down Syndrome Research and Treatment Foundation; Thrasher Foundation; and Alzheimer’s Association.
Ahmad Salehi, M.D., Ph.D.:
An abstract of “Neurobiological Elements of Cognitive Dysfunction in Down Syndrome: Exploring the Role of APP” is posted at <www.biologicalpsychiatryjournal.com/article/S0006-3223(11)00822-5/abstract>.
Wednesday, November 30, 2011
Statistically significant: Vinh Nguyen's contribution to DS research
When the statistician for UC Irvine’s innovative Down syndrome program retired last year, its researchers were left in a bind. The group is studying ways to prevent or delay the onset of Alzheimer’s-type dementia in people with Down syndrome, including examining possible links between seizures and cognitive decline.
“We were mid-study when we found ourselves with no statistician and little budget with which to pay one,” explains program manager Eric Doran.
Statistical analysis for the project was critical and especially difficult. Some of the subjects’ dementia had progressed to the point that they could no longer be tested on performance-based cognitive measures. They couldn’t respond to questions, making it hard for clinicians to evaluate them. But that resulted in missing data. How, then, could the team accurately quantify change over time and see whether seizures might play a role?
Enter Vinh Nguyen, then a doctoral student in statistics at the Donald Bren School of Information & Computer Sciences and now the new head of the UCI Center for Statistical Consulting, which aims to help researchers across campus and Orange County with such challenges. He proposed a model to gauge how quickly people were becoming untestable, instead of how fast they declined. Rather than including test scores – which would have been zero for those who couldn’t be quizzed – Nguyen designed a variable to show when they became unable to respond.
“My part of it was to help them find a way to look at patients with and without seizures, to see if those with seizures might have a shorter time before they became untestable,” he says. “That’s what we found.”Although the findings are preliminary, without his involvement they wouldn’t have been possible. The work resulted in a paper that has been accepted for publication in the Journal of Alzheimer’s Disease. Nguyen, as of October an assistant professor-in-residence of statistics, is a co-author.
“We’re very fortunate to have Vinh’s assistance,” Doran says. “Quite frankly, some of the statistical analysis he’s doing goes well beyond the skill level of even the most seasoned investigators. Vinh was able to pick up where our previous statistician left off, and he was pretty ingenious. His creative look at the data enabled us to complete our analysis.”
Nguyen was glad to help: “I’m excited to be involved in studies that not only advance science but also make a meaningful impact in people’s lives.”
“It’s a huge benefit to the university because it’s free, and it’s a huge benefit to the statistics graduate program because it gives our master’s and Ph.D. students a chance to exercise their knowledge and training in real-world applications,” Nguyen says. “Learning how to communicate, how to collaborate with folks outside your field – you can’t just lecture about that.
It’s got to be a hands-on experience.”
Colleagues say Nguyen, 26 – whose research interests include survival analysis, robust statistical methods, sequential clinical trials and prediction – was the right choice to run the center.
“It’s a big set of responsibilities for someone so young, but he’s got the ability and maturity level to succeed,” says associate professor of statistics Dan Gillen, who directs statistics research at the Institute for Memory Impairments & Neurological Disorders. It was Gillen who introduced Nguyen, whom he was advising on his doctoral thesis, to the Down syndrome team. “Vinh understands the role of statistics across multiple branches of science, and he’s extremely good at translating a seemingly vague hypothesis into a precise statistical framework.”
A native of Vietnam, Nguyen immigrated to the United States at age 5 and grew up in Garden Grove. A true-blue Anteater, he earned all his degrees at UCI, graduating magna cum laude with a B.S. in mathematics and a B.A. in economics, then obtaining an M.S. and a Ph.D. in statistics. In 2010, he received an Achievement Rewards for College Scientists scholar award, which recognizes UCI’s academically superior doctoral students who exhibit outstanding promise as scientists, researchers and public leaders.
“I feel very fortunate to be here,” Nguyen says. “I’m honored to be given this opportunity to lead the center and help it grow, and to work in a field and a setting that allow me to apply my knowledge.”
Wednesday, August 3, 2011
A drug for Down syndrome
from the New York Times:
Early in the evening of June 25, 1995, hours after the birth of his first and only child, the course of Dr. Alberto Costa’s life and work took an abrupt turn. Still recovering from a traumatic delivery that required an emergency Caesarean section, Costa’s wife, Daisy, lay in bed, groggy from sedation. Into their dimly lighted room at Methodist Hospital in Houston walked the clinical geneticist. He took Costa aside to deliver some unfortunate news. The baby girl, he said, appeared to have Down syndrome, the most common genetic cause of cognitive disabilities, or what used to be called “mental retardation.”
Photograph from Alberto Costa
Tyche in kindergarten when she was 5, learning how to write her name.
Costa, himself a physician and neuroscientist, had only a basic knowledge of Down syndrome. Yet there in the hospital room, he debated the diagnosis with the geneticist. The baby’s heart did not have any of the defects often associated with Down syndrome, he argued, and her head circumference was normal. She just didn’t look like a typical Down syndrome baby. And after all, it would take a couple weeks before a definitive examination would show whether she had been born with three copies of all or most of the genes on the 21st chromosome, instead of the usual two.
Costa had dreamed that a child of his might grow up to become a mathematician. He had even prevailed upon Daisy to name their daughter Tyche, after the Greek goddess of fortune or chance, and in honor of the Renaissance astronomer Tycho Brahe. Now he asked the geneticist what the chances were that Tyche (pronounced Tishy) really had Down syndrome.
“In my experience,” he said, “close to a hundred percent.”
Costa and his wife had been trying to have a baby for a couple of years. Daisy’s first pregnancy ended in a miscarriage, which they knew can occur because of a genetic disorder in the fetus. When Daisy became pregnant a second time, Costa insisted they get a chorionic villus sampling, an invasive prenatal genetic test. But the procedure caused a miscarriage. (The test showed that the fetus was genetically normal.) Costa vowed that if there was a third pregnancy — this one — they would conduct no prenatal tests.
Now, with Tyche bundled peacefully in a bassinet at the foot of Daisy’s bed, and Daisy asleep, Costa sat up through most of the night crying. He had gone into the research side of medicine in part to avoid scenes like this — parents devastated by a diagnosis. But by morning, he found himself doing what any father of a newborn might: hovering by the crib, holding his daughter’s hand and marveling at her beauty.
“From that day, we bonded immediately,” he told me during one of our many talks over the last year. “All I could think is, She’s my baby, she’s a lovely girl and what can I do to help her? Obviously I was a physician and a neuroscientist who studies the brain. Here was this new life in front of me and holding my finger and looking straight in my eyes. How could I not think in terms of helping that kid?”
With no experience in the study of Down syndrome, Costa took a short walk the next day to a library affiliated with Baylor College of Medicine, where he worked as a research associate in neuroscience.
Reading the latest studies, he learned that the prognosis was not nearly as dire as it was once considered.
Life expectancies had grown, education reforms had produced marked gains in functioning and — of particular interest to Costa — a mouse model of the disorder had recently been developed, opening the door to experimentation. He soon made a decision: he would devote himself to the study of Down syndrome.
In 2006, using mice with the equivalent of Down syndrome, Costa published one of the first studies ever to show that a drug could normalize the growth and survival of new brain cells in the hippocampus, a structure deep within the brain that is essential for memory and spatial navigation. In people with Down syndrome, the slower pace of neuron growth in the hippocampus is suspected to play a key role in cognitive deficits. Follow-up studies by other researchers reached conflicting results as to whether the drug Costa had tested, the antidepressant Prozac, could produce practical gains on learning tests to match its ability to boost brain-cell growth. Undeterred, Costa moved on to another treatment strategy. In 2007 he published a study that showed that giving mice with Down syndrome the Alzheimer’s drug memantine could improve their memory.
Now Costa has taken the next step: he is completing the first randomized clinical trial ever to take a drug that worked in mice with Down and apply it to humans with the disease, a milestone in the history of Down-syndrome research.
“In my experience,” he said, “close to a hundred percent.”
Costa and his wife had been trying to have a baby for a couple of years. Daisy’s first pregnancy ended in a miscarriage, which they knew can occur because of a genetic disorder in the fetus. When Daisy became pregnant a second time, Costa insisted they get a chorionic villus sampling, an invasive prenatal genetic test. But the procedure caused a miscarriage. (The test showed that the fetus was genetically normal.) Costa vowed that if there was a third pregnancy — this one — they would conduct no prenatal tests.
Now, with Tyche bundled peacefully in a bassinet at the foot of Daisy’s bed, and Daisy asleep, Costa sat up through most of the night crying. He had gone into the research side of medicine in part to avoid scenes like this — parents devastated by a diagnosis. But by morning, he found himself doing what any father of a newborn might: hovering by the crib, holding his daughter’s hand and marveling at her beauty.
“From that day, we bonded immediately,” he told me during one of our many talks over the last year. “All I could think is, She’s my baby, she’s a lovely girl and what can I do to help her? Obviously I was a physician and a neuroscientist who studies the brain. Here was this new life in front of me and holding my finger and looking straight in my eyes. How could I not think in terms of helping that kid?”
With no experience in the study of Down syndrome, Costa took a short walk the next day to a library affiliated with Baylor College of Medicine, where he worked as a research associate in neuroscience.
Reading the latest studies, he learned that the prognosis was not nearly as dire as it was once considered.
Life expectancies had grown, education reforms had produced marked gains in functioning and — of particular interest to Costa — a mouse model of the disorder had recently been developed, opening the door to experimentation. He soon made a decision: he would devote himself to the study of Down syndrome.
In 2006, using mice with the equivalent of Down syndrome, Costa published one of the first studies ever to show that a drug could normalize the growth and survival of new brain cells in the hippocampus, a structure deep within the brain that is essential for memory and spatial navigation. In people with Down syndrome, the slower pace of neuron growth in the hippocampus is suspected to play a key role in cognitive deficits. Follow-up studies by other researchers reached conflicting results as to whether the drug Costa had tested, the antidepressant Prozac, could produce practical gains on learning tests to match its ability to boost brain-cell growth. Undeterred, Costa moved on to another treatment strategy. In 2007 he published a study that showed that giving mice with Down syndrome the Alzheimer’s drug memantine could improve their memory.
Now Costa has taken the next step: he is completing the first randomized clinical trial ever to take a drug that worked in mice with Down and apply it to humans with the disease, a milestone in the history of Down-syndrome research.
“This was a disorder for which it was believed there was no hope, no treatment, and people thought, Why waste your time?” says Craig C. Garner, a professor of psychiatry and behavioral sciences and co-director of the Center for Research and Treatment of Down Syndrome at Stanford University. “The last 10 years have seen a revolution in neuroscience, so that we now realize that the brain is amazingly plastic, very flexible, and systems can be repaired.”
But the effects of that revolution on Down research may yet be cut short. A competing set of scientists are on the cusp of achieving an entirely different kind of medical response to Down syndrome: rather than treat it, they promise to prevent it. They have developed noninvasive, prenatal blood tests which would allow for routine testing for Down syndrome in the first trimester of a pregnancy, raising the specter that many more parents would terminate an affected pregnancy. Some predict that one of the new tests could be available to the public within the year.
Costa, like others working on drug treatments, fears that the imminent approval of those tests might undercut support for treatment research, and even raises the possibility that children like Tyche will be among the last of a generation to be born with Down syndrome.
“It’s like we’re in a race against the people who are promoting those early screening methods,” Costa, who is 48, told me. “These tests are going to be quite accessible. At that point, one would expect a precipitous drop in the rate of birth of children with Down syndrome. If we’re not quick enough to offer alternatives, this field might collapse.”
So recently was the genetic cause of Down syndrome established that just this past March, Costa actually met the widow of the French scientist, Jérôme Lejeune, who made the discovery in 1959. The scene of their meeting was a Paris conference, named in honor of Lejeune, where neuroscientists from around the world discussed progress into treatments for Down and related diseases. Such a conference would have been inconceivable when Costa entered the field 15 years ago.
“If you think about most genetic diseases, they’re usually caused by one gene, and in fact one mutation at one amino acid,” says Roger Reeves, a professor at the Institute for Genetic Medicine at the Johns Hopkins University School of Medicine. “But with Down syndrome, you have an extra copy of all 500 or so genes on Chromosome 21.” In the first two decades after Lejeune’s discovery, the very idea of grappling with those hundreds of triplicated genes scared off scientists from any serious effort to find a treatment for what they were soon calling “trisomy 21.” It just seemed impossibly complex. “The turning point,” Reeves says, “came when Muriel Davisson made her mouse.”
Davisson, now semiretired from Jackson Laboratory in Bar Harbor, Me., spent the 1980s developing a mouse, known as Ts65Dn, that had many of the traits associated with Down syndrome, including, incredibly, the distinctive facial characteristics associated with the disease and the same slightly uncoordinated gait.
Five years after publishing news of her mouse, Davisson received an e-mail from a young neuroscientist named Alberto Costa. Her work, he told her, opened the door for him to conduct meaningful new drug research.
“It was an epiphany, that, oh, this is a field where I can apply a lot that I’ve learned,” Costa says. “Science is usually unforgiving with people who try to change career paths, but it was a risk I was willing to take.” Having earned his Ph.D. studying the electrical and chemical basis of communication between brain cells, “I figured, O.K., if there is something that can be done in this field, it’s going to be done at that level of neuronal electrophysiology.” After months of reading the latest studies, Costa knew he needed Davisson’s mice.
“He twisted my arm till I took him into my lab,” Davisson says with a laugh. “I didn’t have funding. He wrote a grant to get the funding. He is very enthusiastic.” She also found out that he was a “perfectionist, and not very tolerant of people who aren’t perfectionists. He doesn’t do experiments without being sure he’s doing them right. When he makes a finding, you know that it’s real.”
Costa, like others working on drug treatments, fears that the imminent approval of those tests might undercut support for treatment research, and even raises the possibility that children like Tyche will be among the last of a generation to be born with Down syndrome.
“It’s like we’re in a race against the people who are promoting those early screening methods,” Costa, who is 48, told me. “These tests are going to be quite accessible. At that point, one would expect a precipitous drop in the rate of birth of children with Down syndrome. If we’re not quick enough to offer alternatives, this field might collapse.”
So recently was the genetic cause of Down syndrome established that just this past March, Costa actually met the widow of the French scientist, Jérôme Lejeune, who made the discovery in 1959. The scene of their meeting was a Paris conference, named in honor of Lejeune, where neuroscientists from around the world discussed progress into treatments for Down and related diseases. Such a conference would have been inconceivable when Costa entered the field 15 years ago.
“If you think about most genetic diseases, they’re usually caused by one gene, and in fact one mutation at one amino acid,” says Roger Reeves, a professor at the Institute for Genetic Medicine at the Johns Hopkins University School of Medicine. “But with Down syndrome, you have an extra copy of all 500 or so genes on Chromosome 21.” In the first two decades after Lejeune’s discovery, the very idea of grappling with those hundreds of triplicated genes scared off scientists from any serious effort to find a treatment for what they were soon calling “trisomy 21.” It just seemed impossibly complex. “The turning point,” Reeves says, “came when Muriel Davisson made her mouse.”
Davisson, now semiretired from Jackson Laboratory in Bar Harbor, Me., spent the 1980s developing a mouse, known as Ts65Dn, that had many of the traits associated with Down syndrome, including, incredibly, the distinctive facial characteristics associated with the disease and the same slightly uncoordinated gait.
Five years after publishing news of her mouse, Davisson received an e-mail from a young neuroscientist named Alberto Costa. Her work, he told her, opened the door for him to conduct meaningful new drug research.
“It was an epiphany, that, oh, this is a field where I can apply a lot that I’ve learned,” Costa says. “Science is usually unforgiving with people who try to change career paths, but it was a risk I was willing to take.” Having earned his Ph.D. studying the electrical and chemical basis of communication between brain cells, “I figured, O.K., if there is something that can be done in this field, it’s going to be done at that level of neuronal electrophysiology.” After months of reading the latest studies, Costa knew he needed Davisson’s mice.
“He twisted my arm till I took him into my lab,” Davisson says with a laugh. “I didn’t have funding. He wrote a grant to get the funding. He is very enthusiastic.” She also found out that he was a “perfectionist, and not very tolerant of people who aren’t perfectionists. He doesn’t do experiments without being sure he’s doing them right. When he makes a finding, you know that it’s real.”
Using Davisson’s mice, Costa’s 2006 study with Prozac produced cellular changes in the brain. In 2007, Craig Garner at Stanford took the next step, reporting behavioral improvements in Ts65Dn mice after weeks of drug treatment. (Earlier this year, a company he co-founded to pursue that strategy received funding from a venture-capital firm.) Four months later, Costa published his memantine study, showing that a single injection of the drug produced behavioral benefits within minutes, enabling Down-equivalent mice to learn as well as standard mice.
Memantine works, Costa hypothesizes, not by boosting the growth of brain cells but by normalizing how existing cells use the neurotransmitter glutamate. Because people with Down syndrome have three copies of all or most of the genes on Chromosome 21 instead of just two, they have about 50 percent more of any proteins encoded in that chromosome. One result, Costa has shown, is that the NMDA receptors of Ts65Dn mice are “hyperactive” — they overreact to stimuli. By responding to too many things, they learn too little; the signal is lost amid the noise. But giving memantine to quiet the noisy NMDA receptors, Costa has found, makes the brain cells react almost normally.
Other drugs that work on different systems in the brain have also shown benefits in the Ts65Dn mouse. In 2009, Dr. William C. Mobley, chairman of neurosciences at the University of California, San Diego, and one of the most active and visible researchers in the field, co-wrote a study showing that a combination of drugs designed to raise norepinephrine levels in the brain normalized the mice’s learning abilities. Most recently, last year the Nobel laureate Paul Greengard of Rockefeller University showed that memory and learning could be normalized in Ts65Dn mice by lowering levels of beta amyloid, the protein goop that has long been known to clog the brains of people with Alzheimer’s disease.
“There’s been a sea change in our ability to understand and treat Down syndrome,” Mobley says.
“There’s just been an explosion of information. As recently as the year 2000, no drug company would possibly have thought about developing therapies for Down syndrome. I am now in contact with no less than four companies that are pursuing treatments.”
Costa’s current memantine study began by testing memory and spatial learning in 40 young adults with Down syndrome. Daily, for 16 weeks, half received memantine pills, the other half a placebo. This fall, Costa will present preliminary results at a scientific meeting in Illinois on whether taking the drug made those with Down, in a word, smarter.
A half-hour from his office and laboratory at the University of Colorado-Denver School of Medicine, where he is an associate professor of medicine and neuroscience, Costa pulled into a parking space in front of his modest two-bedroom apartment. The figure of a girl in green dashed toward the car — and then vanished.
“Tyche,” Costa called to his daughter, “where’d you go?”
We both stepped out to look for her. I found her standing in front of another car, a Subaru Forester, waiting to get in. Dressed in a lime-colored shirt and skirt, the bangs of her mahogany hair framed by a hair band, Tyche stood just 4 feet 6 inches tall, with a round face, broad nose and heavy-lidded eyes.
Seeing my puzzled look, Costa explained that they also owned the Subaru — which he usually drove with Tyche. He led her to the Toyota we’d arrived in, where she sat down in the back seat. As Costa drove us to his office, I asked what she thought of her father’s work.
“He’s the greatest scientist,” she said, in a slurred, high-pitched voice. Then she added with a laugh, “And he builds evil machines.”
“That’s from watching too many cartoons,” Costa said. “Her favorite is ‘Phineas and Ferb.’ Of course, there’s an evil scientist in it who builds all kinds of machines.”
Other drugs that work on different systems in the brain have also shown benefits in the Ts65Dn mouse. In 2009, Dr. William C. Mobley, chairman of neurosciences at the University of California, San Diego, and one of the most active and visible researchers in the field, co-wrote a study showing that a combination of drugs designed to raise norepinephrine levels in the brain normalized the mice’s learning abilities. Most recently, last year the Nobel laureate Paul Greengard of Rockefeller University showed that memory and learning could be normalized in Ts65Dn mice by lowering levels of beta amyloid, the protein goop that has long been known to clog the brains of people with Alzheimer’s disease.
“There’s been a sea change in our ability to understand and treat Down syndrome,” Mobley says.
“There’s just been an explosion of information. As recently as the year 2000, no drug company would possibly have thought about developing therapies for Down syndrome. I am now in contact with no less than four companies that are pursuing treatments.”
Costa’s current memantine study began by testing memory and spatial learning in 40 young adults with Down syndrome. Daily, for 16 weeks, half received memantine pills, the other half a placebo. This fall, Costa will present preliminary results at a scientific meeting in Illinois on whether taking the drug made those with Down, in a word, smarter.
A half-hour from his office and laboratory at the University of Colorado-Denver School of Medicine, where he is an associate professor of medicine and neuroscience, Costa pulled into a parking space in front of his modest two-bedroom apartment. The figure of a girl in green dashed toward the car — and then vanished.
“Tyche,” Costa called to his daughter, “where’d you go?”
We both stepped out to look for her. I found her standing in front of another car, a Subaru Forester, waiting to get in. Dressed in a lime-colored shirt and skirt, the bangs of her mahogany hair framed by a hair band, Tyche stood just 4 feet 6 inches tall, with a round face, broad nose and heavy-lidded eyes.
Seeing my puzzled look, Costa explained that they also owned the Subaru — which he usually drove with Tyche. He led her to the Toyota we’d arrived in, where she sat down in the back seat. As Costa drove us to his office, I asked what she thought of her father’s work.
“He’s the greatest scientist,” she said, in a slurred, high-pitched voice. Then she added with a laugh, “And he builds evil machines.”
“That’s from watching too many cartoons,” Costa said. “Her favorite is ‘Phineas and Ferb.’ Of course, there’s an evil scientist in it who builds all kinds of machines.”
“Like the Smell-inator,” added Tyche, who turned 16 in June.
Back at Costa’s office, Tyche demonstrated to me what people with Down can be capable of even without medication. (Because she’s not an adult, Tyche is ineligible to participate in her father’s study.)
On the whiteboard at the front of the room, Costa wrote out an algebra problem for her to solve: 8x2 - 7 = 505.
“She’s one of only two people with Down syndrome who I’ve ever known to be capable of doing algebra,” Costa said. “Normally we give her a problem before she goes to bed.” As she solved the equation, taking six steps to conclude that X equals 8, he said, “It’s basically instead of a bedtime story.”
This past Christmas, he proudly noted, he gave her the Rosetta Stone language program for learning Portuguese, and by March she had finished with Level 1 and begun Level 2.
It turns out that with vigorous education and support, many people with Down do far better than once thought possible. Medical care of heart and other physical ailments associated with the disorder have likewise achieved significant benefits, doubling the average lifespan from 25 to 49, in just the 14 years between 1983 and 1997.
Still, with an I.Q. that is typically around 50 points lower than average — with some far lower and others, like Tyche, reaching higher — something more than education alone would be necessary to enable the majority of people with Down syndrome to live independently. Costa said he hopes that memantine might be that something, raising I.Q. noticeably, even if modestly. For him, the goal is to help people with Down syndrome achieve autonomy. “At some point, you want your children to have their own life,” he said. “It’s about independence.”
Costa was raised in Brazil, the son of a marine officer and a seamstress. When he was 14, his parents divorced. His father sent little support, and he and his two siblings lived with their mother in poverty. Perhaps inevitably for someone who had to struggle to rise above his circumstances, he comes across as intense and consumed by his work; he hasn’t taken a vacation since Tyche was 3. But he is also devoted to his daughter and wife, spending most of every weekend with them.
“She’s a great kid,” he said. “She has a very strong personality. In many ways she has features of a regular teenager. She doesn’t like me to get into her bedroom. She loves pop music and vampires.” Her relatively high functioning, he told me, is important to him. “If Tyche were really severely affected, I don’t know if I would have had the energy to go on with this business.” Then again, he admits to having paternal feelings toward all 40 young adults in his study, whose cognitive abilities vary widely. “At the end of the day,” he said, “their parents know someone really cares for their kid. It’s not an academic experience for me. It’s my life.”
In January, and again in March, a spate of news reports described new studies of the noninvasive blood tests that would allow pregnant women to check for Down syndrome without the risks and discomfort associated with chorionic villus sampling and amniocentesis. Few of the articles, however, took note of the profound unease many medical ethicists, including some who are ardently pro-choice, feel about the tests and how they might lead to a dramatic reduction in the Down syndrome population.
“Even people who are traditionally against abortion are sometimes willing to condone it when the abortion is of a fetus with a disabling trait,” says Erik Parens, a bioethicist at the Hastings Center in Garrison, N.Y. “But it’s important to recognize that there is a huge range of genetic disorders. In their own way, a lot of kids with Down syndrome flourish, and so do their families.”
Advocates of the new tests insist that parents will be given news of an affected pregnancy by a trained geneticist who will present the information fairly and fully. Critics, including Costa and many other parents of children with Down syndrome, say that such dispassionate approaches rarely happen in practice, with many obstetricians and genetic counselors providing unduly negative or misleading information.
But Stephen Quake, a professor of bioengineering and applied physics at Stanford and a developer of one of the new tests, says: “It’s a gross oversimplification to assume that these tests are going to lead to the wholesale elimination of Down-syndrome births. My wife’s cousin has Down syndrome. We just celebrated his 21st birthday. He’s a wonderful person. It’s not an obvious step that you would terminate an affected pregnancy.”
On the whiteboard at the front of the room, Costa wrote out an algebra problem for her to solve: 8x2 - 7 = 505.
“She’s one of only two people with Down syndrome who I’ve ever known to be capable of doing algebra,” Costa said. “Normally we give her a problem before she goes to bed.” As she solved the equation, taking six steps to conclude that X equals 8, he said, “It’s basically instead of a bedtime story.”
This past Christmas, he proudly noted, he gave her the Rosetta Stone language program for learning Portuguese, and by March she had finished with Level 1 and begun Level 2.
It turns out that with vigorous education and support, many people with Down do far better than once thought possible. Medical care of heart and other physical ailments associated with the disorder have likewise achieved significant benefits, doubling the average lifespan from 25 to 49, in just the 14 years between 1983 and 1997.
Still, with an I.Q. that is typically around 50 points lower than average — with some far lower and others, like Tyche, reaching higher — something more than education alone would be necessary to enable the majority of people with Down syndrome to live independently. Costa said he hopes that memantine might be that something, raising I.Q. noticeably, even if modestly. For him, the goal is to help people with Down syndrome achieve autonomy. “At some point, you want your children to have their own life,” he said. “It’s about independence.”
Costa was raised in Brazil, the son of a marine officer and a seamstress. When he was 14, his parents divorced. His father sent little support, and he and his two siblings lived with their mother in poverty. Perhaps inevitably for someone who had to struggle to rise above his circumstances, he comes across as intense and consumed by his work; he hasn’t taken a vacation since Tyche was 3. But he is also devoted to his daughter and wife, spending most of every weekend with them.
“She’s a great kid,” he said. “She has a very strong personality. In many ways she has features of a regular teenager. She doesn’t like me to get into her bedroom. She loves pop music and vampires.” Her relatively high functioning, he told me, is important to him. “If Tyche were really severely affected, I don’t know if I would have had the energy to go on with this business.” Then again, he admits to having paternal feelings toward all 40 young adults in his study, whose cognitive abilities vary widely. “At the end of the day,” he said, “their parents know someone really cares for their kid. It’s not an academic experience for me. It’s my life.”
In January, and again in March, a spate of news reports described new studies of the noninvasive blood tests that would allow pregnant women to check for Down syndrome without the risks and discomfort associated with chorionic villus sampling and amniocentesis. Few of the articles, however, took note of the profound unease many medical ethicists, including some who are ardently pro-choice, feel about the tests and how they might lead to a dramatic reduction in the Down syndrome population.
“Even people who are traditionally against abortion are sometimes willing to condone it when the abortion is of a fetus with a disabling trait,” says Erik Parens, a bioethicist at the Hastings Center in Garrison, N.Y. “But it’s important to recognize that there is a huge range of genetic disorders. In their own way, a lot of kids with Down syndrome flourish, and so do their families.”
Advocates of the new tests insist that parents will be given news of an affected pregnancy by a trained geneticist who will present the information fairly and fully. Critics, including Costa and many other parents of children with Down syndrome, say that such dispassionate approaches rarely happen in practice, with many obstetricians and genetic counselors providing unduly negative or misleading information.
But Stephen Quake, a professor of bioengineering and applied physics at Stanford and a developer of one of the new tests, says: “It’s a gross oversimplification to assume that these tests are going to lead to the wholesale elimination of Down-syndrome births. My wife’s cousin has Down syndrome. We just celebrated his 21st birthday. He’s a wonderful person. It’s not an obvious step that you would terminate an affected pregnancy.”
But Costa points to a falloff in the financing of Down-syndrome research since the prenatal tests have been in development. Although it’s difficult to compare the numbers, money from the National Institutes of Health dropped to $16 million in 2007 from $23 million in 2003, before creeping back up to $22 million in 2011. That’s far less than the $68 million slated for cystic fibrosis, which affects an estimated 30,000 people in the United States, at most one-tenth of the 300,000 to 400,000 people who have Down.
“The geneticists expect Down syndrome to disappear,” Costa says, “so why fund treatments?”
Alan Guttmacher, director of the National Institute of Child Health and Human Development, denies that this is the calculus used by his organization. Yet he offered no clear answer when I asked him why about $3,000 in research dollars is spent by N.I.H. for every person with cystic fibrosis, compared with less than $100 for every person with Down.
“The number affected is a fair metric to use,” Guttmacher said. But, he pointed out, most of N.I.H.’s funding decisions are based on the strength of proposals coming from researchers. Advocacy groups for disorders like AIDS, autism and breast cancer have certainly played a role in their gaining increased funding, he said. And perhaps, he speculated, Down suffers from an image problem. “Part of it is that Down syndrome has been around for so long,” he said.
Representative Cathy McMorris-Rodgers, Republican of Washington, who co-founded the Congressional Down Syndrome Caucus soon after her 4-year-old son, Cole, was born with the disorder, has had little success in having money appropriated for Down research.
“I find myself wondering how N.I.H. really sets their priorities,” she told me. “I’m quite concerned that so many of the researchers in the Down-syndrome field have difficulty getting funded.” She continued, “My fear is that for some, they believe that it’s been taken care of through prenatal diagnosis.”
Even Costa has struggled to secure financing. He lives with Tyche and Daisy in a rented apartment, having never felt he had enough job security to buy a home. At his laboratory, some of his most expensive and sophisticated equipment for studying Down syndrome remains in storage, literally gathering dust for want of financing to use it. One source of his research money has been the Anna and John J. Sie Foundation, based nearby in Denver, and run by Michelle Sie Whitten, whose 8-year-old daughter has Down syndrome. Three years ago, the foundation established a research institute at the University of Colorado in Denver, where Costa works.
Plainly, though, he didn’t get into Down-syndrome research for the money. “There’s a reason why I’m doing what I’m doing,” he told me, nodding toward Tyche.
Not all parents of children with Down syndrome embrace Costa’s vision of a medical treatment targeting intelligence. In a recent survey conducted in Canada, parents were asked what they would do if there was a “cure” for their child’s Down syndrome. A surprising 27 percent said they would definitely not use it, and another 32 percent said they were unsure.
Meanwhile, the major not-for-profit advocacy groups devoted to Down syndrome spend little on research, instead preferring to lobby and offer parental support. Fresh energy has come from two relatively new groups determined to turn the situation around — Research Down Syndrome and the Down Syndrome Research and Treatment Foundation — but even they have so far succeeded in each raising only about $1 million a year, a fraction of the annual research budgets of many other disease-advocacy groups.
Behind the ambivalence toward treatments, some parents say, is a fear that increasing their children’s intelligence might change their personalities — their very identities.
“Nobody would be against giving insulin for diabetes,” said Michael Bérubé, director of the Institute for the Arts and Humanities at Pennsylvania State University and author of the 1996 book “Life as We Know It,” published five years after his second son, Jamie, was born with the disorder. “But Down syndrome isn’t diabetes or smallpox or cholera. It’s milder and more variable and more complicated. I’d be very leery of messing with the attributes Jamie has. He’s pretty fabulous. At the same time, I’m not doctrinaire. If you’re talking about a medication that allows people to function in society and hold jobs, how can you be against that?”
The parents I met whose children participated in Costa’s study expressed little of Bérubé’s ambivalence. Peggy Hinkle told me about changes she saw in her 26-year-old daughter. “When Christina was on the pills, she told me one morning about a dream she had. She gave me five full, complete sentences. Which is a very big deal. Not only that, she left the room and came back later and told me another sentence about the dream. And she started to do Jumble word puzzles in the newspaper. I don’t know if she was on the drug or on placebo, but after five weeks there was a change. Boom. That’s why we participated: to expand her horizons.”
Alan Guttmacher, director of the National Institute of Child Health and Human Development, denies that this is the calculus used by his organization. Yet he offered no clear answer when I asked him why about $3,000 in research dollars is spent by N.I.H. for every person with cystic fibrosis, compared with less than $100 for every person with Down.
“The number affected is a fair metric to use,” Guttmacher said. But, he pointed out, most of N.I.H.’s funding decisions are based on the strength of proposals coming from researchers. Advocacy groups for disorders like AIDS, autism and breast cancer have certainly played a role in their gaining increased funding, he said. And perhaps, he speculated, Down suffers from an image problem. “Part of it is that Down syndrome has been around for so long,” he said.
Representative Cathy McMorris-Rodgers, Republican of Washington, who co-founded the Congressional Down Syndrome Caucus soon after her 4-year-old son, Cole, was born with the disorder, has had little success in having money appropriated for Down research.
“I find myself wondering how N.I.H. really sets their priorities,” she told me. “I’m quite concerned that so many of the researchers in the Down-syndrome field have difficulty getting funded.” She continued, “My fear is that for some, they believe that it’s been taken care of through prenatal diagnosis.”
Even Costa has struggled to secure financing. He lives with Tyche and Daisy in a rented apartment, having never felt he had enough job security to buy a home. At his laboratory, some of his most expensive and sophisticated equipment for studying Down syndrome remains in storage, literally gathering dust for want of financing to use it. One source of his research money has been the Anna and John J. Sie Foundation, based nearby in Denver, and run by Michelle Sie Whitten, whose 8-year-old daughter has Down syndrome. Three years ago, the foundation established a research institute at the University of Colorado in Denver, where Costa works.
Plainly, though, he didn’t get into Down-syndrome research for the money. “There’s a reason why I’m doing what I’m doing,” he told me, nodding toward Tyche.
Not all parents of children with Down syndrome embrace Costa’s vision of a medical treatment targeting intelligence. In a recent survey conducted in Canada, parents were asked what they would do if there was a “cure” for their child’s Down syndrome. A surprising 27 percent said they would definitely not use it, and another 32 percent said they were unsure.
Meanwhile, the major not-for-profit advocacy groups devoted to Down syndrome spend little on research, instead preferring to lobby and offer parental support. Fresh energy has come from two relatively new groups determined to turn the situation around — Research Down Syndrome and the Down Syndrome Research and Treatment Foundation — but even they have so far succeeded in each raising only about $1 million a year, a fraction of the annual research budgets of many other disease-advocacy groups.
Behind the ambivalence toward treatments, some parents say, is a fear that increasing their children’s intelligence might change their personalities — their very identities.
“Nobody would be against giving insulin for diabetes,” said Michael Bérubé, director of the Institute for the Arts and Humanities at Pennsylvania State University and author of the 1996 book “Life as We Know It,” published five years after his second son, Jamie, was born with the disorder. “But Down syndrome isn’t diabetes or smallpox or cholera. It’s milder and more variable and more complicated. I’d be very leery of messing with the attributes Jamie has. He’s pretty fabulous. At the same time, I’m not doctrinaire. If you’re talking about a medication that allows people to function in society and hold jobs, how can you be against that?”
The parents I met whose children participated in Costa’s study expressed little of Bérubé’s ambivalence. Peggy Hinkle told me about changes she saw in her 26-year-old daughter. “When Christina was on the pills, she told me one morning about a dream she had. She gave me five full, complete sentences. Which is a very big deal. Not only that, she left the room and came back later and told me another sentence about the dream. And she started to do Jumble word puzzles in the newspaper. I don’t know if she was on the drug or on placebo, but after five weeks there was a change. Boom. That’s why we participated: to expand her horizons.”
For his part, Costa has no doubts about the work to which he has devoted the last 15 years of his life. “If you have a disorder that’s changing the function of an organ, which in this case is the brain, and you use a medication to bring the function of that organ closer to where it was meant to be from millions of years of evolution, that’s as fair as treating any other disease,” he said. “I don’t see it as any different.” If his current study is successful, Costa’s ultimate goal is to test it in youths, like Tyche, during the crucial early years of development. Costa is quick to point out that he has not offered her memantine outside the study, and he discourages other physicians from doing so until its safety and effectiveness is proved. But from his perspective as both a researcher and a father, he said: “The sooner you start, obviously, the greater would be your hopes. All I know is, the clock is ticking.”
Tuesday, August 2, 2011
Scientist tests promising drug on those with Down syndrome
from Health Canal:
A University of Colorado School of Medicine scientist is finishing a major clinical trial on a drug that could boost cognitive function in those with Down syndrome, significantly improving their quality of life and representing a potential milestone in research on this genetic disorder.
A University of Colorado School of Medicine scientist is finishing a major clinical trial on a drug that could boost cognitive function in those with Down syndrome, significantly improving their quality of life and representing a potential milestone in research on this genetic disorder.
“We are hoping to enhance memory and learning in those with Down syndrome,” said Alberto Costa, MD, Ph.D., an associate professor of medicine and the neuroscientist leading the effort.
“We have been studying this drug for three years and are now ready to analyze the data on our trial. Our team at the University of Colorado and Children’s Hospital Colorado expects to have the results in the next two or three months.”
Costa, whose work was chronicled in last Sunday’s New York Times Magazine, (A Drug for Down Syndrome), is tested the drug memantine, currently used to relieve symptoms of Alzheimer’s disease, in 39 people with Down syndrome. About half received the drug and the others a placebo. In 2007, Costa demonstrated that memantine could improve memory function in mice with Down syndrome.
And now, for the first time, he is taking a drug effective in the treatment of learning and memory deficits in mice with Down syndrome and applying it to humans, a move described by the New York Times as “a milestone in the history of Down syndrome research.”
Costa is no disinterested researcher, his 16-year-old daughter Tyche – named for the Greek goddess of Fortune - has Down syndrome. Like others with the condition, she faces the specter of a steady decline in mental functioning as she gets older and a roughly 20 percent chance of getting Alzheimer’s in her 50’s. After that diagnosis, death is often just five years away.
“I feel I am racing the clock to find something that will at least keep her functioning at the level she is at now,” Costa said. “As they age, parts of their brain will shrink and their functions will diminish.”
Costa is actively pursuing links between Down and Alzheimer’s disease. He says babies born with Down often carry the biological markers for Alzheimer’s.
“They have the disease from the get go,” he said.
Costa says the world is awash in false assumptions about Down syndrome ranging from distortions on life expectancy to educational limitations. In fact, depending on the severity of their condition, those with Down can live into their 70s, attend college, live independently and hold down jobs.
“If we are successful, it will increase hope and expectations for those with Down syndrome,” Costa said. “Right now there are drugs for the signs and symptoms of medical conditions more frequent in those with Down syndrome, but nothing to improve brain function. In fact, the prevailing wisdom has been that there is essentially nothing you can do to boost memory and learning in this group. Hopefully, we can prove them wrong.”
But he and other Down researchers face an overall lack of federal funding, especially when compared to other diseases and disorders.
Costa has been supported by Forest Pharmaceuticals which is funding the clinical trial, the Linda Crnic Institute for Down Syndrome, the Coleman Institute for Cognitive Disabilities at the University of Colorado and the National Institute of Child Health and Development, part of the National Institutes of Health.
“Clearly these funding sources are the unsung heroes,” Costa said. “They may not get the attention or publicity but I can assure you that our efforts and the future of those with Down syndrome would be seriously compromised without their continued generosity.”
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