A Quarter Century of Disease-Focused Neuroscience

A quarter century ago, in September 1998, Gladstone Institutes launched the Gladstone Institute of Neurological Disease. In 2023, it brought together investigators and alumni to celebrate the institute’s 25th anniversary, reflect on landmark scientific achievements, and look ahead at the future of disease-focused neuroscience.

The institute—led by Lennart Mucke, MD, since its inception—began with a keen focus on Alzheimer’s disease. While staunchly maintaining this focus, the institute has since expanded its research program to include Huntington’s disease, Parkinson’s disease, multiple sclerosis, epilepsy, autism, and other brain disorders.

Today, diseases that affect the brain or other parts of the central nervous system are among the most disabling and complex conditions plaguing humankind. As populations around the world are living longer, aging-related neurodegenerative disorders have been rising in prevalence at an unprecedented pace.

“Our scientists have unraveled key mechanisms that lead from genetic risk factors to neurological decline and have identified therapeutic strategies to block them,” says Mucke. “I am thrilled that several of these groundbreaking discoveries have culminated in the development of novel treatments and their evaluation in clinical trials.”

“Part of the reason so many drugs for brain diseases have failed over the last decades is that we didn’t have a sufficient understanding of the disease processes,” says Deepak Srivastava, MD, president of Gladstone Institutes. “I’m proud that we’ve taken a rigorous mechanistic approach to understanding these processes at a deep level, since that’s what it takes to design more successful therapies that can actually help patients and their families.”

From Discovery to Translation

Since 1998, trailblazing studies carried out by researchers at the Gladstone Institute of Neurological Disease revealed how amyloid and tau proteins, as well as apolipoprotein E4 (the most important genetic risk factor for Alzheimer’s disease), conspire to erode precious brain functions. The investigators also discovered how specific blood proteins and inflammatory processes promote neurodegeneration, and how to block the vicious circle between neural network and immune dysfunctions that fuels the progression of Alzheimer’s disease, epilepsy, and related conditions.

These landmark discoveries, and many others, were presented on September 15, 2023, as part of the symposium “Disease-Focused Neuroscience: From Discovery to Translation.” The event also included presentations by former Gladstone investigators who now lead major research centers at Stanford University and Weill Cornell Medicine, as well as a panel discussion on the future of biomedicine and translational neurobiology.

“GIND, over the past 25 years, has thought about putting patients first in all of their discoveries,” said S. Andrew Josephson, MD, Chair of the Department of Neurology at UC San Francisco, in his closing remarks at the symposium. “The work done here is not only about understanding fundamental neuroscience, but it’s also about curing these terrible diseases for which, in many cases, we still don’t have effective treatments. That’s what made today so inspiring.”

The symposium highlighted many translational efforts to advance Gladstone’s basic research discoveries toward the clinic, including two drugs for Alzheimer’s disease and related conditions that are currently in clinical trials and that were identified by investigators at the Gladstone Institute of Neurological Disease.

In the past 15 years alone, eight spin-out companies have been launched leveraging Gladstone technologies, and scientists have formed partnerships with large biotechnology and pharmaceutical companies, including AstraZeneca, Biogen, BMS, Eli Lilly, Genentech, Gilead, Google, Lundbeck, Merck, Sanofi, and Takeda Pharmaceuticals.

Supporting Scientists and Their Passions

The celebrations ended with a reception for scientists and close partners at the Fairmont San Francisco. During the evening, Dagmar and David Dolby were presented with this year’s Gladstone Trustees Award in recognition of their long-standing support of neurological disease research at Gladstone.

The Dolby family has made significant donations in support of Gladstone’s Alzheimer’s disease research since 2016, and has also helped create Cure Network Dolby Acceleration Partners to develop novel therapeutics for this disease.

“I feel very privileged to have the opportunity to support Gladstone scientists and their passions, and I’m proud to feel part of the advances they made over the past decade,” says David Dolby. “Knowing this is a complex topic, they take a multi-pronged approach to neurodegenerative diseases while also exploring frontiers that are distinguished in the field.”

“My family and I placed our trust in Gladstone, and we’ve been delighted by their focus on translation to help develop actual therapies that can eventually make it into the clinic,” he adds.