Tag: Ideas & Perspectives

Alana Down Syndrome Center at the 2024 World Down Syndrome Congress

The power of inclusive research
EventsIdeas & PerspectivesJuly 31, 2024
Panelist Jaspreet Kaur Sekhon shakes hands with the host, Professor Rhonda Faragher at the World Down Syndrome Congress.
Jaspreet Kaur Sekhon and Professor Rhonda Faragher at a plenary session featuring ADSC

In Brisbane, Australia, the World Down Syndrome Congress convened in-person for the first time since 2018. Over 1000 delegates from 45 countries met from July 9th – 12th, 2024, for the central theme of “Together We Can: Celebrating Diversity and Inclusion.” The event allowed families, advocates and professionals from the global Down syndrome community to gather and discuss all aspects of health, research, education, employment, inclusion and personal development. The Alana Down Syndrome Center (ADSC) of MIT was honored to be featured in a plenary session focused on the center’s ongoing research supported by the Alana Foundation.

The session, chaired by Professor Rhonda Faragher, was not a typical scientific meeting, as it included self-advocates and families as participants in the discussion. Panelists included Jaspreet Kaur Sekhon from Singapore who has overcome adversity as a leading self-advocate for Down syndrome. Her long list of accolades includes a keynote presentation at the United Nations, and decades of dance performance and instruction for young people with disabilities. Jessamy Tang, MIT graduate and Managing Director of the Stanford Down Syndrome Research Center, and Nathan Rowe, Program Director at Down Syndrome International, rounded out the panel with their deep expertise in disability inclusion.

An image of the panel members, host and speaker seated at the discussion table on stage.
The plenary session panel (left to right): Jessamy Tang, Jaspreet Kaur Sekhon, Nathan Rowe, Rhonda Faragher, Rosalind Firenze.

 

The program director of ADSC, Dr. Rosalind Firenze, featured the work of the center and highlighted the recent clinical study, led by Dr. Diane Chan and Picower Professor Li-Huei Tsai, Director of the ADSC and The Picower Institute for Learning and Memory of MIT. Tsai’s group is developing a ground-breaking, non-invasive therapy for Alzheimer’s disease known as ‘GENUS’ – gamma entrainment through non-invasive 40Hz sensory stimulation. The landmark clinical trial, the first to study the effects of GENUS in people with Down syndrome, was recently completed at MIT. The results are currently being analyzed with initial outcomes indicating that light and sound stimulation can increase the strength of 40Hz gamma rhythms in the brain and may provide cognitive benefits in the short-term. Long-term studies in people with Down syndrome and Alzheimer’s disease are still needed to test the therapeutic efficacy of this non-invasive approach.

 

Firenze also highlighted another MIT invention: ZzAlign, which is a comfortable, mouth-piece device under development to help people with obstructive sleep apnea (OSA) keep airways open. The new device incorporates digital intraoral scans, 3D printing technology and an innovative smart-pump design to apply a gentle suction pressure to hold the tongue in place, effectively opening airways during sleep. OSA impacts the majority of adults with Down syndrome and impacts their overall health. The development of ZzAlign is led by Professor Ellen Roche‘s lab and the Deshpande Center for Technological Innovation. The team is currently entering clinical trials to test the device’s efficacy during sleep in people with OSA.

 

Families and self-advocates learned about other ADSC research, including the use of iPSC (induced pluripotent stem cell) models to study changes in heart development and application of GENUS to improve neurodevelopment in the T65Dn mouse model of Down syndrome.  After learning about the research tools and progress, audience members participated in an engaging discussion on the role of scientific research in attaining a higher quality of life for people with Down syndrome. Sekhon pointed out the importance of including self-advocates in research design and discussions to ensure that their needs are considered and incorporated. Tang further championed the concept of consulting with families in the early stages of clinical trial design to ensure that participation is accessible and comfortable. Rowe also pointed out that once technologies and therapies are developed it is important to make them available in a fair and equitable way. Audience members asked questions about how the model systems relate back to people with Down syndrome and when therapies like GENUS might become available.

By connecting the Down syndrome community directly to cutting-edge research at MIT, the plenary session felt momentous with an important take-away: inclusivity can push science further. Jaspreet Kaur Sekhon said it best herself, as she thanked researchers at ADSC and the panel, “You all were very inclusive, in giving me this Voice and listening to me.”

Blending complementary expertise, Tsai and Kellis labs tackle brain diseases

Pair brings a team science approach to Down syndrome, Alzheimer's and other conditions
Ideas & PerspectivesPeopleResearchMarch 1, 2019
An illustration of a brain in profile overlaid with binary code

Li-Huei Tsai is a neuroscientist and Manolis Kellis is a computer scientist, so by working together, their research teams are able to ask questions about the big data of the brain that neither one could alone.

In their collaboration to help elucidate and mitigate Alzheimer’s disease and other neurological conditions, the labs of neuroscientist Li-Huei Tsai and computer scientist Manolis Kellis are two sides of the same coin on two sides of Vassar Street.

Bringing complementary skills to a shared mission as part of MIT’s Aging Brain Initiative and Alana Down Syndrome Center, the team seamlessly blends and advances some of the hottest and most powerful methods in science – statistical genetics, computational genomics, epigenomics, machine learning, single-cell profiling, “big data” integration, induced stem-cell reprogramming, mini-brain organoids, tissue engineering, and CRISPR-Cas9 genetic manipulation.This allows their teams to study genetic and molecular differences between healthy and diseased samples from multiple brain regions of humans and mice, integrate and analyze the resulting data to identify significant disease-driver genes and the cell types where they act, and engineer cells, tissues and mouse models to test their hypotheses and discover therapeutic interventions.

“Working together, we have the opportunity to garner big data from a large number of human subjects to elucidate the driver genes and pathways that are novel but key to the disease,” said Tsai, Picower Professor and director of the Picower Institute for Learning and Memory. “We can then test these genes/pathways in the induced pluripotent stem cells (iPSC) system coupled with CRISPR-Cas9 to manipulate the genome. We can induce the iPS cells into all major brain cell types, and dissect the contributions of each of these cell types to disease.”

It’s a joint research venture that’s as close, cutting-edge, and multidisciplinary as any at MIT, and fits squarely within the Schwarzman College of Computing’s emphasis on integrating artificial intelligence with the sciences. Kellis recalls it all getting started back in 2012 via the connection of postdocs, Elizabeth Gjoneska of the Tsai Lab and Andreas Pfenning from the Kellis Lab, who had met at a seminar on campus. With similarly overlapping interests in how gene regulation, and specifically epigenomic differences, affect the workings and health of the brain, they and other members of the two labs kindled dialogues that soon brought the professors together.

“The collaboration kind of happened organically,” said Kellis, professor of computer science and head of MIT’s Computational Biology Group. “We found kindred spirits – folks who thought similarly but were extremely complementary in their expertise.”

Within two years, the labs had jointly published two major papers. One in Nature, part of a sweeping set of reports on epigenomics that Kellis helped lead, showed that highly analogous sets of gene misregulation signals in the hippocampus of mice and humans each revealed a strong role for the brain’s immune cells and processes in allowing Alzheimer’s disease to progress. The other paper, in Cell, showed that in order to rapidly express genes critical for experience to affect synaptic connections, neurons naturally employ double-strand breaks of their DNA. The team hypothesized that failure to repair these breaks increases with age and may also contribute to neurodegeneration.

Each paper demonstrated the power of their combined approach. Since then, the collaboration has grown significantly to encompass about half a dozen projects. In 2016, for instance, they earned a National Institutes of Health grant to determine the significant epigenomic differences afoot in major brain cell types in Alzheimer’s disease.

In the last year, Kellis and Tsai received an influx of several new NIH grants and philanthropic gifts,  such as the one establishing the Alana Down Syndrome Center, enabling them to substantially expand their efforts in Alzheimer’s, tackle new disorders, bring in new collaborators, include new types of experiments, and expand their mechanistic studies. Their new directions include Schizophrenia, Bipolar Disorder, Psychosis in Alzheimer’s Disease, Frontotemporal Dementia, Lewy Body Dementia, and healthy aging.

Importantly, each experiment is designed together, Kellis says. Knowing that the team combines the capabilities of each lab, the team can be more ambitious.

“We think in a different way than any one lab would think by itself,” Kellis said. “For instance, I wouldn’t have the guts to ask many of these things that we are asking, if it wasn’t for our close collaboration with Li-Huei’s lab.”

In the Alana Center, they will apply their team science approach to modeling and analyzing Down syndrome, looking to identify and dissect the unique genetic and molecular signals that explain how the presence of an extra chromosome 21 affects the brain.

And with the new NIH grants, they will ask a litany of questions such as why many people with Alzheimer’s develop psychotic symptoms as well, what are the unique molecular signatures that distinguish Alzheimer’s and other dementias, and how do specific genetic variations in non-coding DNA elevate risk for a number of neurodegenerative and neuropsychiatric disorders.

“How privileged I feel to work with the world’s best computational team,” Tsai said. “This is only possible at MIT.”