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Symposium examines intersecting biology of neurodegeneration, Down syndrome

Cross-cutting examples of disease pathology, cellular breakdowns highlight joint conference

Talk Videos

Watch videos of several of the symposium talks on YouTube.

Neuroscientists still have a tremendous amount to learn about the causes and courses of neurodegenerative diseases and Down syndrome, but as speakers at the Oct. 5-6 MIT symposium “Glial and Neuronal Biology of the Aging Brain” pointed out, often when they make a new discovery in the context of one such condition, it teaches them something relevant to others.

“Our belief is that the study of the aging brain can learn a great deal from the study of Down syndrome and vice versa,” said Picower Professor Li-Huei Tsai who directs the two MIT entities that jointly hosted the conference: The Aging Brain Initiative and the Alana Down Syndrome Center. “It would be a wonderful outcome of this symposium if we can play even a small role in bringing these two communities of scientists, physicians, and engineers, and even caregivers closer together.”

The event indeed marshaled a multitude of online attendees. Over the course of the two-day program more than 400 people tuned in from 27 countries. They heard scientists from places as far-ranging as Hong Kong and Germany share their latest research and discuss the many intersections they see among Alzheimer’s and other dementias, Parkinson’s disease, Huntington’s disease and Down syndrome.

For example, Tracy Young Pearse, associate professor of neurology at Harvard Medical School and Brigham and Women’s Hospital, discussed her lab’s new finding that the three copies of the genes APP and DYRK1A found in Down syndrome neurons (because they have three copies of chromosome 21), increase phosphorylated tau (a pathological hallmark of Alzheimer’s) and promote excessive transport and release of neurotransmitters across connections with other neurons, a potential source of circuit dysfunction.

Vessels of concern

Though neural circuits remain at the heart of brain function, three speakers instead focused their talks on the brain’s circulatory system. MIT Associate Professor Myriam Heiman noted that the breakdown of the blood-brain barrier, which strictly filters what the body and brain exchange, are suspected of being key contributor to many neurodegenerative diseases. In presenting her lab’s new research that produced a novel “atlas” of cell types in the brain’s blood vessels, she showed clear evidence that vascular integrity is weakened in Huntington’s disease and that the degradation is associated with a problematic innate immune response.

Elizabeth Head, Professor of pathology and laboratory medicine at the University of California at Irvine, related dysfunction of brain vasculature to the connection between Down syndrome and Alzheimer’s. Though people with Down syndrome are relatively protected against cardiovascular problems such as high blood pressure or atheroma, an excess of amyloid protein in their brain blood vessels leads to cerebral amyloid angiopathy, a condition closely associated with Alzheimer’s. Head’s lab has shown that people with Down syndrome and CAA exhibit microbleeds along their brain blood vessels.

Head collaborates with Adam Brickman, professor of neuropsychology at Columbia University. He presented recent studies showing that magnetic resonance imaging of “white matter hyperintensities” and other vascular problems can be a biomarker of Alzheimer’s pathology in people with Down syndrome. The hyperintensities, which the team showed to be especially prevalent in posterior lobes of the brain, are believed to be the result of brain vasculature problems and correlated with other problems such as microbleeds.

Symposium speaker Adam Brickman and moderator and former Alana Fellow Jackie Yang

Cells not immune from scrutiny

Several other speakers focused on the brain’s immune cells, called microglia, which have a very complex role in neurodegenerative diseases including Alzheimer’s.

Microglia, for instance, take on many different states in Alzheimer’s ranging from beneficial to harmful. In her talk, Harvard Medical School & Boston Children’s Hospital neurology Associate Professor Beth Stevens described methods her lab has developed for culturing microglia from stem cells and then coaxing them into these many states by tailoring either their genetic background, their environmental context, or both.

Li Gan, professor of neuroscience at Weill Cornell Medicine, discussed particular instances in which molecularly manipulating microglial state can sustain the brain’s resilience to Alzheimer’s pathology. In a study published earlier this year her lab found that by reducing expression of the gene transcription factor NFkappaB in microglia, the lab could reduce spreading of the problematic protein tau. She also shared even newer results showing that intervening in a specific runaway immune pathway in microglia by knocking down a key molecule, her lab has shown benefits in learning and memory in mice. The method appears to do so by increasing activity of a resilience-promoting transcription factor called MEF2 that Tsai’s lab has also independently identified as beneficial.

Hong Kong University of Science and Technology Professor Nancy Yuk-Yu Ip detailed another molecular method of helping microglia combat Alzheimer’s. Her lab has found that in the disease a soluble form of the molecule ST2 intercepts the immune molecule interleukin 33 (IL-33), which would normally prompt a transition of microglia into a beneficial state. The lab has shown that injecting IL-33 improves Alzheimer’s pathology in mice and has found a genetic variant in people that conveys protection against this problem.

Three images are stacked in the frame. Across the top are head and shoulders pictures of Michael Heneka on the left and Ravi Raju on the right. They are listening as Li-Huei Tsai (on the bottom) speaks.
MIT Professor Li-Huei Tsai asks a question while speaker Michael Heneka, director of the Luxembourg Centre for Systems Biomedicine, and moderator Ravi Raju, an MIT postdoc, listen.

In his talk, Michael Heneka, director of the Luxembourg Centre for Systems Biomedicine, showed how microglia literally throw neurons a line to help them fight back against toxic proteins. His lab found that microglia extend “tunneling nanotubes” to neurons beset with tau (a toxic aggregate in some dementias) or alpha-synuclein (a toxic aggregate most prevalent in Parkinson’s disease) to remove the proteins and to supply neurons with fresh mitochondria to rescue them from oxidative stress.

A system with many parts

Neurons, vascular cells, and microglia were not the only cells with time in the spotlight. Shane Liddelow, assistant professor of neuroscience and physiology at New York University focused on astrocytes, an abundant cell type in the brain with key roles in supporting neural function and linking neurons to blood vessels. He shared new research indicating that subtypes of astrocytes have inflammatory responses in disease and in the case of Alzheimer’s, associate with pathology in particular parts of the brain. Further research can help determine what those subtypes may matter to the progression of the disease.

Astrocytes, neurons and microglia were all featured in the remarks of Gilbert Di Paolo, executive director of discovery biology at Denali Therapeutics. He discussed the company’s potential therapy for a subset of cases of frontotemporal dementia. In those cases, mutations reduce levels of progranulin, which undermines the function of cells’ lysosomes. By restoring levels of progranulin in cells the company is restoring lysosomal function and therefore indicators of cell health.

Complementing the talks’ exposition of the variety of cell types and molecular mechanisms at issue across neurodegenerative diseases and Down syndrome were the posters of MIT postdocs and graduate students that followed the talks. A dozen presenters from seven labs affiliated with the Aging Brain Initiative, the Alana Center, or both highlighted whole systems approaches to understanding and treating disease. Members of Tsai’s lab, for instance, discussed the therapeutic possibilities for Down syndrome of stimulating the brain with light and sound at the key frequency of 40Hz. Members of the labs of Professors Ed Boyden and Alan Jasanoff presented new advances in brain imaging. Members of Professor Manolis Kellis’s lab showed how sophisticated computational approaches can help demystify the genetic complexities of Down syndrome. A poster representing the lab of Professor Ernest Fraenkel highlighted molecular networks related to neurodegeneration. And members of the labs of Professors Ann Graybiel and Matthew Wilson highlighted neural mechanisms fundamental to behavior and memory.

The symposium offered all these scientists, and their hundreds of audience members, the chance to virtually gather and learn from each other at a crossroads of intersecting disease biology.

Upcoming Alana Down Syndrome/Aging Brain Initiative Symposium

Research symposium Oct. 5 & 6th on Glial and Neuronal Biology of the Aging Brain
Cells labeled in green & blue cluster in interesting 'rosette' patterns
The Alana Down Syndrome Center aims to deepen knowledge about Down syndrome and to improve health, autonomy and inclusion of people with this genetic condition.
The Aging Brain Initiative is an interdisciplinary effort by MIT focusing on understanding neurodegeneration and discovery efforts to find hallmarks of aging, both in health and disease.
The ADSC and the ABI are teaming up for a joint symposium, focusing on the challenges of aging brains in cognitively normal adults, and the overlap with aging for people with DS.

The topic of this symposium is Glial and Neuronal Biology of the Aging Brain


Event Registration



This symposium will take place virtually over the course of two days: October 5 and October 6. The talks on October 5 will take place in the afternoon EST and the October 6 talks will take place in the morning EST. The event is open to the public and free to attend though registration will be required. Be on the lookout for registration emails and more information on this page as the event date approaches.
Confirmed Speakers:

Upcoming Webinar: Technology to Improve Ability

Join us Wednesday, June 16 at 12:00pm ET
a woman with down syndrome works on a laptop

The ADSC presents an update on our Technology to Improve Ability Grant program. These talks will be accessible to the general public.

Featured Talks:

A Novel Device For Obstructive Sleep Apnea In Down Syndrome

(Ravi Rasalingam and Tarsha Ward of the Ellen Roche group)


Commalla: Augmentative Communication Tech using Naturalistic Data and Machine Learning

​(Kristina Johnson and Jaya Narain of the Pattie Maes and Rosalind Picard groups)


Registration is free, but required: https://mit.zoom.us/webinar/register/WN_MhEkEpxzQnyXqJ55OFnx0g

Down syndrome symposium highlights clinical, fundamental progress

Speakers describe studies to address Alzheimer’s disease, sleep apnea and to advance fundamental discoveries
Li-Huei Tsai stands at an MIT podium with the Alana Center logo in the background
Alana Center co-director Li-Huei Tsai, speaking at a previous center event.

Whether they are working with patients in clinical trials or with chromosomes in cell cultures, scientists and physicians in the Boston area and beyond are testing a wide variety of new ways help people with Down syndrome. At the New England Down Syndrome Symposium, presented by the Alana Down Syndrome Center on Nov. 10, a virtual audience of hundreds of people learned about the research progress of a dozen research teams. The Alana Center at MIT partnered with the Massachusetts Down Syndrome Congress and the LuMind IDSC Foundation to organize the daylong program of online talks.

“I am hopeful that the research being done today will improve medical care and the quality of life of people with Down syndrome,” said Kate Bartlett, a member of the Self-Advocate Advisory Council of the MDSC. “Your work is important for me and my peers. Together we can make a better world for all people to lead active, healthy, fulfilling lives.”

Clinical studies

One of the specific health concerns Bartlett, who is 35, called out in her remarks is that the age of onset for Alzheimer’s disease among people with Down syndrome can be as early as 40. Finding ways to address the community’s elevated risk of Alzheimer’s was one of the four main themes of the symposium, along with new potential therapies for sleep apnea, and fundamental research on developmental biology and on chromosome number and dosage.

Li-Huei Tsai presents two mouse brain scans side by side. One has more white spots than the other.
Alana Center co-director Li-Huei Tsai presents research showing that 40Hz light and sound stimulation reduces amyloid plaques, a hallmark of Alzheimer’s pathology. The research team hopes this can help people with Down syndrome, who have an elevated risk of the disease.

MIT is poised to launch a clinical study of a potential Alzheimer’s therapy among people with Down syndrome, said Alana center co-director Li-Huei Tsai, Picower Professor of Neuroscience at MIT. About five years ago her lab discovered that in Alzheimer’s brain wave power and connectivity at a specific frequency, 40Hz, is notably lessened. They discovered that by exposing lab mice to light flickering and sound buzzing at 40Hz they could restore the rhythm, leading to many benefits including improved learning and memory, reduced neuron death and reductions in the level of toxic tau and amyloid proteins considered hallmarks of Alzheimer’s pathology.

More recently the team has begun clinical studies of the potential therapy, called Gamma ENtrainment Using Sensory Stimuli (GENUS), in humans to test its safety and efficacy in healthy people and in people with Alzheimer’s. Picower Clinical Fellow Diane Chan, the neurologist leading the human studies, said that so far the data indicate that exposure to 40Hz light and sound is safe and may be contributing to improved sleep and a preservation of brain volume in patients with mild Alzheimer’s disease. As soon as conditions related to the Covid-19 pandemic allow, she said, the team will invite people with Down syndrome to enroll in a study to test safety, tolerability and efficacy specifically for them.

Two speakers from Massachusetts General Hospital tackled the important related issue of diagnosing and tracking the progression of Alzheimer’s specifically in people with Down syndrome. Stephanie Santoro, a clinical geneticist with the hospital’s Down syndrome program, described the nationwide LIFE-DSR study, which counts Bartlett among its participants. The study has rigorously developed a suite of assessments to track changes in cognition, behavior, function and health in 270 adults of various ages with Down syndrome over a course of more than 30 months, Santoro said. The results will offer doctors and patients new insights into how aging and Alzheimer’s affect life over time, which may help in screening for Alzheimer’s risk.

Diana Rosas, an MGH neurologist, is one of the researchers helping to run the LIFE-DSR study. In her talk she focused on another study, the National Institute of Health’s ABC-DS study, in which she is developing biomarkers that may indicate the onset of mild cognitive impairment and Alzheimer’s in Down syndrome including data from brain scans, molecule and protein levels measured in blood, and genetic screens. She noted that these markers seeking to track changes over time need to be specific for Down syndrome patients, for instance because they have characteristic differences in brain anatomy compared to people who don’t have the condition.

Diana Rosas shows a slide comparing two brain scans made up of color coded lines
MGH neurologist Diana Rosas recently published a study showing differences in brain connectivity among Down syndrome patients with (right) and without Alzheimer’s disease (left).

Another challenge that can hinder learning, memory and cognition in people with Down syndrome is loss of sleep due to breathing trouble. Two symposium speakers discussed new approaches to treating the problem, called sleep apnea, which is very common in people with Down syndrome because of characteristics such as decreased muscle tone, differences in facial anatomy, and larger tongue size. Daniel Combs, a pediatrician at the University of Arizona, described a trial he recently began to test a combination of drugs to treat sleep apnea in children with Down syndrome. The medicines he’s testing have been studied for sleep apnea in non-Down syndrome adults and appear to be helping by increasing airway muscle tone, he said.

Massachusetts Eye and Ear Infirmary otolayrngologist Christopher Hartnick, meanwhile, discussed a surgical approach he is testing for difficult sleep apnea cases. Called hypoglossal nerve stimulation, the procedure involves implanting a breathing sensor on a rib that leads to a processor further up the chest. The processor then stimulates electrodes on muscles of the tongue.  When the patient is drawing a breath (sensed at the rib) the processor stimulates the tongue muscles to move the tongue out of the way to improve air flow. This approach has been successful in adults with DS and sleep apnea. So far, Hartnick said, 33 children have been implanted and results look promising.

Fundamental research

At the same time that all of these clinical trials have been progressing, other researchers have been working in the lab to advance more fundamental understanding of the biology going on in cells of people with Down syndrome, often also called trisomy 21 because it is caused by having a third copy of chromosome 21.

Some researchers have forged ahead by working to develop better mouse models of Down syndrome that can more closely reproduce the biology of the condition in the lab. Tarik Haydar of the Center for Neuroscience Research at Children’s National Hospital in Washington DC described his lab’s recent study showing how variations in a predominant mouse model called Ts65dn have led to differing and sometimes contradictory research conclusions that need to be recognized and accounted for.

While important nuances about the Ts65dn model are becoming better understood, Elizabeth Fisher of University College London shared that new mouse models are emerging. In mice the genes that are on human chromosome 21 are spread out over three chromosomes. That has given researchers the challenge of engineering mice to express genes in the same way that people with Down syndrome do. Fisher’s lab has led advances in doing so, and she reported that recently another group managed to directly inserting human chromosome 21 into mice to develop a new model, the TcMAC21 mouse.

Mouse models are crucial because they are whole living organisms that can demonstrate how health and behavior change with an extra chromosome. But another way to model Down syndrome in the lab is by engineering human cell cultures from cells taken from patients. Skin cells, for instance, can be turned into stem cells, which in turn can grow into neurons or heart cells.

MIT biology Professor Laurie Boyer, for instance, has begun studying gene expression in heart muscle cells derived from Down syndrome (DS) persons. The development of the heart is a very intricate and sensitive process and faulty regulation leads to congenital heart defects (CHD). Her goal is to learn how an extra copy of chromosome 21 in DS contributes to the high incidence of CHD that will hopefully fuel potential new therapies for these heart defects.

In other experiments with patient-derived cells—in this case, neurons—Lindy Barrett of the Broad Institute of MIT and Harvard is finding intriguing overlaps between Down syndrome and a form of autism called Fragile X syndrome. Her lab is finding that the protein missing in Fragile X, called FMRP, normally regulates some genes that are also expressed too much in Down syndrome. The findings, she said, raise the question of whether manipulating levels of FMRP could help Down syndrome patients.

While individual genes, or groups of them, could present new targets for therapies, another goal of the field remains finding a way to repress the activity of the third chromosome 21 as a whole. Speakers Jeanine Lee and Mitzi Kuroda, each of Harvard Medical School, described mechanisms by which various organisms, including humans, naturally suppress or enhance whole-chromosome activity. Females have two X chromosomes but males have an X and a Y. To remedy that imbalance, insects like fruit flies doubly express the X chromosome in males but mammals, like people, suppress or “silence” the activity of one of the X chromosomes in females.

This unusual degree of whole-chromosome up- or down-regulation offers intriguing scientific opportunities. Lee discussed how she hopes to address an autism-like disorder called Rett Syndrome in which girls develop abnormally because a mutant copy of the gene MeCP2 happens to be on one X chromosome they express. Her strategy is to selectively subvert X-chromosome silencing to express the healthy copy of MeCP2 on the inactivated X chromosome. Meanwhile speaker Stefan Pinter of the University of Connecticut discussed how his lab is using the X-chromosome’s silencing machinery to silence the extra chromosome 21 in Down syndrome. Pinter said that by silencing the third copy in developing brain cells in the lab his research group is developing a dynamic model for lab studies in which they can now control chromosome 21 dosage in developing brain cells.

In wrapping up the symposium, Alana Center faculty member Ed Boyden, Y. Eva Tan Professor of Neurotechnology at MIT, said the day provided many individual examples of progress that taken together are even more encouraging.

“Today we have seen many individual examples of research and advocacy from which we can draw inspiration and hope,” he said. “But there is another source of those same feelings as well: the way this community came together today to share and to learn from each other. Even if our interaction was virtual, the growth in our understanding and our interconnection was real.”

The Alana Center Presents: The New England Down Syndrome Symposium

Symposium Nov. 10 features a day of presentations on the latest research
Li-Huei Tsai stands at an MIT podium with the Alana Center logo in the background

On November 10, 8:45 a.m. to 4 p.m., join us for a series of stimulating talks addressing some of the latest research in New England and beyond.

This event will be held online. Registration is free but required. Click here to register.

If you have registered, click here to view the symposium.

A poster for the New England Down Syndrome Symposium showing speaker names and logos of the organizers

This event was co-organized by The Alana Down Syndrome Center, The Massachusetts Down Syndrome Congress and The Lumind IDSC Foundation


8:45 – 9:00am Introduction (featuring remarks from Kate Barlett, MDSC Self-Advocate Advisory Council)

Session 1: Developmental biology

9:00 – 9:40am Elizabeth Fisher (keynote), University College London : Working with mouse models to understand Down syndrome

9:40 – 10:05am Laurie Boyer, MIT, Getting to the Heart of Down Syndrome

10:05 -10:30am Tarik Haydar, Center for Neuroscience Research, Children’s National Hospital, Variation in phenotypic presentation of mouse models of Down syndrome, findings and implications

10:30 -10:55am Lindy Barrett, Broad Institute, MIT and Harvard, Probing molecular convergence between Down syndrome and Fragile X syndrome

10:55 – 11:10am Break

Session 2: Alzheimer’s Disease in Down Syndrome – Recent Advances

11:10 -11:35am Diana Rosas, Massachusetts General Hospital Neurology

11:35am – 12:00pm Stephanie Santoro Massachusetts General Hospital Down Syndrome Program, LIFE-DSR study and assessment scales for AD in DS

12:00 -12:25pm Li-Huei Tsai and Diane Chan, Alana Down Syndrome Center at MIT, Leveraging Brain Rhythms As A Therapeutic Intervention For Alzheimer’s Disease

12:25 – 12:45pm Tribute to Angelika Amon (featuring remarks from Li-Huei Tsai, Claudia Moreira, Manolis Kellis, Laurie Boyer, Brian Skotko, Ed Boyden, and Emily Niederst)

12:45 – 1:30pm Lunch

Session 3: Dosage compensation/aneuploidy

1:30 -2:10pm Jeannie Lee (keynote), Harvard Medical School, Manipulating X-chromosome dosage to treat human disorders

2:10 – 2:35pm Stefan Pinter , University of Connecticut, Trisomy 21 silencing: Towards a dynamic in vitro model of Down Syndrome

2:35 – 3:00pm Mitzi Kuroda, Harvard Medical School , X chromosome dosage compensation in Drosophila

3:00 – 3:15pm Break

Session 4: Sleep Apnea in Down Syndrome

3:15 – 3:40pm Daniel Combs, University of Arizona, Medications for Obstructive Sleep Apnea in Children with Down Syndrome

3:40 – 4:05pm Christopher Hartnick, Harvard Medical School, HGN Implant for Severe Sleep Apnea: Where are we now?

4:05 pm Closing Remarks and Angelika Amon Tribute Video

Tsai lab webinar at Mass Down Syndrome Congress

3 members of ADSC to give webinar for virtual Annual Conference
A young man gestures while holding a microphone and speaking

Translating Down Syndrome Neuroscience Research

Tuesday, July 28, 2020 10-11am EST

As people with Down syndrome age, the risk of developing Alzheimer’s disease (AD) increases significantly. The Tsai Lab discovered that by boosting gamma power, we could reverse AD related pathology and improve memory in mouse models of AD & DS. We developed a device that boosts gamma power in people using light and sound to improve memory in AD patients and individuals with Ds. In addition, the lab is using human pluripotent stem cells to generate the different types of cells in the brain, to study the mechanisms of how Trisomy 21 has such a large impact on brain function.

This webinar will not be recorded, so please plan to join live.

Diane Chan, MD PhD, Neurologist, Massachusetts Institute of Technology/Massachusetts General Hospital; Brennan Jackson, BS, Doctoral Student, Massachusetts Institute of Technology; Hiruy Meharena, PhD, Alana Senior Fellow, Massachusetts Institute of Technology


Logos for MDSC and MIT


Down Syndrome symposium presents bench-to-bedside research

First annual symposium brings together local Down Syndrome research community
Angelika Amon speaks at a podium
ADSC co-director Angelika Amon speaks about her work

At its first ever symposium Nov. 6, the Alana Down Syndrome Center demonstrated ways, from the scale of chromosomes to that of caregiving communities, that scientists and physicians in Massachusetts and around the country are working to help people with Down syndrome live their healthiest, fullest lives.

Founded at MIT in March 2019, the ADSC brings together neuroscience, biology, engineering and computer science research labs together with the Desphande Center for Technological Innovation to deepen knowledge about Down syndrome and to improve health, autonomy and inclusion of people with the genetic condition characterized by an extra copy of chromosome 21.

The symposium, “Translational Research in Down Syndrome,” brought together experts working across a spectrum of fundamental biology to clinical care.  In her opening remarks, ADSC co-director Li-Huei Tsai, Picower Professor of Neuroscience and director of The Picower Institute for Learning and Memory, said the event represented a chance for conversation and collaboration among researchers with the common goal of helping people with Down syndrome.

“Informed and inspired by their remarks we can all engage today in learning from each other,” she said. Tsai also thanked Ana Lucia Villela, whose Alana Foundation gift established the center and who had returned to MIT from Brazil to attend the symposium.

‘Aneuploidy’ advances

Throughout the afternoon, speakers shared some of their latest insights into how “aneuploidy,” having an atypical number of chromosomes, alters the biology of cells, the body and the brain.

One consequence appears to be that with an extra chromosome, cells make too many copies of the protein subunits that the chromosome encodes. Normally these subunits would become bound with partners encoded elsewhere into larger protein complexes, said ADSC Co-Director Angelika Amon, Kathleen and Curtis Marble Professor of Cancer Research in MIT’s biology department and the Koch Center for Integrative Cancer Research. But there aren’t as many of those partners, so the excess, unbound proteins become prone to clumping together, creating a major clean-up job for the cells that causes ”proteotoxic” stress. In Down syndrome, she said, that stress can hinder growth and proper function. Aneuploidy, she added, might also lead to a greater incidence of DNA damage.

Professors Reeves, Espinosa, Torres, Amon & Tsai pose for the camera
Professors Reeves, Espinosa, Torres, Amon & Tsai enjoy the meeting

Former Amon lab postdoc Eduardo Torres, who is now at the University of Massachusetts Medical School, said his lab has found that aneuploidy also disrupts the very shape and structure of the nucleus in a variety of cells, making them more sensitive to mechanical stress. The lab looked deeper to find the genetic and molecular pathway responsible and identified one related to the lipid composition of the nucleus. That insight allowed them to discover that administering certain drugs to cells with aneuploidy of chromosome 21 (or 13 or 18) can help shore up the nuclear structure and help cells grow.

To gain more insight into how aneuploidy affects neurological development many scientists have begun using techniques to grow brain cells from stem cells derived from Down syndrome patients. They can manipulate these cultures in the lab so that the only genetic difference is the extra copy of chromosome 21. Jeanne Lawrence, also of UMass, said use of such advanced models will help her understand whether a technique her lab has developed to silence extra copies of a chromosome will be effective in cells such as those in the brain or blood. Her work shows promise for a potential gene therapy to mitigate the effects of the extra copy of chromosome 21.

Another vital model of Down syndrome is the mouse. In one of the day’s two keynote addresses, Roger Reeves of the McKusick-Nathans Institute for Genetic Medicine at Johns Hopkins University described what researchers have learned from the widely used T65dn mouse model, as well as what they hope to learn from a newly developed model, that uses human chromosome 21 genes to replicate chromosome duplication. He also described their studies of the developmental anomalies in Down syndrome model mouse brains, and have found that a crucial signaling pathway for development is less responsive in these mice. He reported the results of a screen to look for the specific contributors this pathway in DS, as they may be viable targets for drug development, and his lab has also identified some of these same genes to be involved in congenital heart defects.

Clinical care

In the symposium’s other keynote, Joaquin Espinosa of the Linda Crnic Institute for Down Syndrome at the University of Colorado, discussed how a fast-emerging raft of insights including discoveries about the immune system in Down syndrome has led to a new clinical trial. Fundamental research at the institute has found that patients with Down syndrome have an increased sensitivity to interferons, proteins emitted by immune cells as they fight infections. The research led scientists to test medicines to calm the immune system. He described their current work on a clinical trial that aims to investigate a drug, Xeljanz, already used for auto-immune disease, to see if the drug not only improves autoimmune skin diseases, but possibly a wider range of symptoms associated with Down syndrome.

Another clinical trial is getting underway at Boston Children’s Hospital, said Nicole Baumer, a researcher there who said there are real opportunities for interventions to improve cognition in Down syndrome patients, but who also cautioned that researchers must always consult patients and their caregivers about what they want from clinical trials and care, rather than assuming what’s best for them. After surveying to learn more about patient and family wishes, her group has designed a study in which they will try to predict the neurodevelopmental outcomes in babies with Down syndrome, and test whether behavioral therapy interventions designed for certain autism populations might also augment intellectual development in children with Down syndrome.

Dr. Brian Skotko presents a new program from his clinic

As researchers strive in the lab and clinic to make new discoveries and improve care, Brian Skotko of Massachusetts General Hospital and Harvard Medical School has also been considering how to ensure that state-of-the-art information reaches doctors and family caregivers everywhere it’s needed. Skotko noted that among approximately 212,000 people with Down syndrome in the United States, less than five percent have access to one of the 71 specialty clinics around the country like the one he directs at MGH. Instead, they typically depend on primary care physicians. That’s why he and a diverse team have spent the last two years developing an Internet-based platform, “Down Syndrome Clinic to You (DSC2U)” in which a physician or other caregiver can enter information about a patient and learn richly linked, expert-curated information and recommendations about medical care and wellness customized for the entered patient profile. The clinical team at MGH reviews the underlying database regularly to keep it up to date. With new data showing that the system positively influences care and has been valued by users, it’s ready for a wider launch next year, he said.

Taken together, the symposium talks illustrated many routes to potential progress, from the cell to the clinic.