Breaking barriers in brain health

How the Wyss Institute is advancing targeted therapies, early diagnosis, and collaborative models to confront neurodegenerative disease, mental illness, and brain cancer

For decades, some of the most urgent challenges in brain health have resisted progress across both academia and the pharmaceutical industry. At the Wyss Institute, we are tackling them head-on.

A central focus is overcoming one of the field’s biggest obstacles: delivering drugs effectively to the brain and central nervous system. Today, this process remains inefficient, limiting treatment options for neurodegenerative diseases, psychiatric disorders, and brain cancers. At the same time, we are developing technologies to detect these diseases earlier – before symptoms appear – opening the door to more timely and effective interventions. Addressing these complex challenges requires not only technological innovation but also new models of collaboration that span disciplines and sectors.

Making brain delivery possible

A major hurdle in treating brain disorders is the blood-brain barrier (BBB), which prevents many promising drugs from reaching their targets. The Wyss Brain Targeting Program (BTP) is tackling this challenge through a novel pre-competitive collaboration model that brings together multiple industry partners.

After five years of development, the program is delivering results. Its brain transport “shuttles,” designed to carry therapeutics across the BBB, now match or exceed leading industry technologies and have already been licensed to five major companies, with more agreements underway. With continued support from partners and sponsors, the BTP is advancing its platform by optimizing delivery for disease-specific therapies, enhancing next-generation shuttle designs, and identifying new BBB targets for improved transport.

Over the past year, the program has:

• Added four new industry sponsors, including ABL-Bio, GSK, and Leal
• Executed six licensing agreements with leading biotech and pharmaceutical companies
• Expanded access to its brain transport mouse models (now 18 agreements)
• Launched new discovery collaborations with OmniAb and Alloy Therapeutics
• Initiated efforts to improve the delivery of oligonucleotide therapies, including ASOs and siRNAs
• Convened two industry partnership meetings
• Prepared two peer-reviewed manuscripts for publication

Expanding the science of anesthesia

Through a Wyss-led collaboration supported by DARPA’s Anesthetics for Battlefield Care (ABC) program, researchers are uncovering the neurological mechanisms of anesthesia and using AI to design safer drugs. Led by Founding Director Don Ingber, M.D., Ph.D., and Senior Scientist Haleh Fotowat, Ph.D., in collaboration with Harvard, the Massachusetts Institute of Technology (MIT), and Tufts University, the team is developing anesthetics that require less monitoring, an advance that could save thousands of lives on the battlefield and in disaster settings.

Detecting disease earlier

Many neurodegenerative diseases begin long before symptoms appear. Detecting them earlier could dramatically improve patient outcomes. The team of Core Faculty member David Walt, Ph.D., is pioneering “liquid biopsy” approaches using extracellular vesicles (EVs), tiny particles released by brain cells that carry disease biomarkers.

Senior Scientist Dmitry Ter-Ovanesyan, Ph.D., and other members of Walt’s team devised an assay to clearly distinguish molecules contained in EVs from molecules non-specifically bound to their surface, solving a ubiquitous problem confounding the entire EV field. In addition, former Wyss Associate Research Fellow and Lumineer Tal Gilboa, Ph.D., who is now Co-Founder & Head of Research at Everest Biolabs, and the team developed a single-molecule detection method to enable ultra-sensitive measurements of a pathological form of ɑ-synuclein, a sign of Parkinson’s disease, in EVs. This work has helped launch Everest Biolabs, which is developing advanced tools for EV isolation and analysis.

The team has also secured support from the Robert Packard Center for ALS Research, The Michael J. Fox Foundation, and Open Philanthropy to develop early detection methods for ALS, enabling better disease tracking and evaluation of new therapies.

Advancing treatments for bipolar disorder

The CircaVent team, led by Director of Synthetic Biology Jenny Tam, Ph.D., and Core Faculty member George Church, Ph.D., with neuroscience and nanotechnology expertise from Senior Scientists Katharina Meyer, Ph.D., and Ninning Liu, Ph.D., is developing new therapeutic strategies for bipolar disorder. By creating patient-specific brain organoids that replicate key disease features, the team is identifying shared biological signatures and testing drugs that could normalize them. Supported by BD² (Breakthrough Discoveries for Thriving with Bipolar Disorder), the effort aims to translate these findings into new treatments in collaboration with clinical experts at Massachusetts General Hospital and Harvard Medical School.

The team is actively seeking partners to expand CircaVent into a broader drug discovery platform for bipolar disorder and other mental health conditions.

Brain-Targeted Therapeutics Catalyst

Building on the success of its brain shuttle technology, the Brain Targeting Program is launching the Brain-Targeted Therapeutics Catalyst, an initiative designed to accelerate the development of brain-targeted drugs. Led by Senior Director of Translational R&D James Gorman, M.D., Ph.D., the Catalyst will make the shuttle platform widely accessible to academic, industry, and government researchers, supported by a venture philanthropy fund. Donors will share in royalties from successful therapies, aligning impact with return. The initiative aims to advance treatments for:

• Alzheimer’s disease
• Parkinson’s disease
• ALS
• Brain tumors
• Enzyme disorders
• Neuropsychiatric conditions