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MD Anderson is known for its cancer care and research. But did you know that for more than a decade, MD Anderson researchers have been working on better treatments for Alzheimer’s disease and other age-related neurodegenerative diseases, too?

Launched in 2012 through a $25 million gift from Robert Belfer and the Belfer family, the Belfer Neurodegeneration Consortium (BNDC) is a multi-institutional initiative between MD Anderson, the Massachusetts Institute of Technology (MIT), the Icahn School of Medicine at Mount Sinai in New York, Baylor College of Medicine and New York University, among others. The consortium was established to gain a deeper understanding of neurodegenerative diseases and translate those findings into effective therapeutic interventions.

Unparalleled drug discovery and development expertise

The Belfer Neurodegeneration Consortium is a core part of MD Anderson’s Therapeutics Discovery division, which brings together scientists, clinicians and drug development experts to eliminate the bottlenecks stifling traditional drug discovery and advance effective new therapies in ways only possible here at MD Anderson.

In Fiscal Year 2023, MD Anderson had more NCI-funded projects than any other U.S. institution and the world’s largest cancer clinical trials program. MD Anderson also helped to evaluate nearly 60% of the new drugs approved by the Food and Drug Administration last year.

“Very few places have this breadth and scope of drug discovery,” says Jim Ray, Ph.D., executive director of the Belfer Neurodegeneration Consortium. “The Therapeutics Discovery division is essentially a mid-sized biotech company within an academic hospital.”

Alzheimer’s disease and age-related diseases could affect future cancer research and care

When the Belfer Neurodegeneration Consortium was formed, Alzheimer’s was rapidly becoming a major health care crisis and was projected to account for 50% of the total U.S. health care economy by 2050. Today, nearly 7 million people are estimated to be living with Alzheimer’s disease, and 1 in 3 adults over age 65 will develop dementia. And, the risk for Alzheimer’s and other neurodegenerative diseases goes up drastically after age 85.

“In addition to the tremendous suffering it causes, Alzheimer's is also the most expensive disease in the United States. Patients need full-time family support or round-the-clock care in specialized centers,” Ray says. “As the population ages, we won't be able to support the number of people who need care.”

MD Anderson’s leadership and donors foresaw how this diversion of health care resources could affect future cancer patients. If limited health care resources were tied up with caring for patients with neurodegenerative diseases, that could affect future funding for cancer research and care.

Alzheimer’s disease and cancer have unexpected connections

Given the brain’s unique environment and the fact that cancer and Alzheimer’s disease share risk factors and have similar biological pathways of disease, many therapies the Belfer Neurodegeneration Consortium studies for Alzheimer’s also may have potential for treating cancer.

“We are constantly discovering unexpected connections between Alzheimer’s and cancer,” Ray says. “By studying the fundamental causes of neurodegenerative diseases, we hope to develop therapies that promote nervous system health and function in cancer patients, too.”

For example, he points to the similarities between the memory-related side effects of chemotherapy, commonly referred to as chemobrain, and the dementia experienced by Alzheimer’s patients. The Belfer Neurodegeneration Consortium observed cancer and Alzheimer’s patients’ brains both exhibited the activation of a protein called DLK, which senses injury to neurons and kills damaged brain cells, leading to cognitive impairment. Similarly, patients also share similar inflammatory responses in the brain’s immune cells called microglia, which differ from immune cells found in the rest of the body. Together, these biological responses contribute to the memory loss and nerve damage experienced by both cancer patients and Alzheimer’s patients.

That’s why the consortium is helping launch the NeuroHealth Initiative at MD Anderson to study the brain and the nervous system – beginning with ovarian cancer patients – to understand what happens when patients develop memory loss and neuropathy during chemotherapy and radiation treatment.

Ray says this provides a unique lens for studying the early stages and underlying mechanisms of neurodegeneration because, unlike with Alzheimer’s, researchers will be able to study cancer patients before their first treatment and thus, before the onset of their first symptoms.

Early breakthroughs show promise for next-generation Alzheimer’s therapies

Just as the last decade saw immunotherapy, targeted therapy and advanced diagnostics extend the lives of cancer patients, Ray believes now is also a critical time for treatment advances for Alzheimer’s.

“For the first time, we have agreement in the field that it is possible to slow the disease,” he says. “To do this, we need multiple ways to attack the disease, as well as a deep understanding of what's driving each patient's dementia, so that we can have personalized medicine for Alzheimer’s.”

Over the past decade, the Belfer Neurodegeneration Consortium has pursued over 40 drug discovery projects, with five advancing to the next stage. From this research, they have established four keys to treating Alzheimer’s:

• Introduce neuroprotective agents to keep brain cells from dying
• Address genetic risk factors like APOE4 before patients show symptoms of Alzheimer’s disease
• Lessen the inflammatory response of microglia, the brain’s immune cells
• Combat the toxicity of tau proteins that cause amyloid plaque tangles in the brain

Encouraged by the Belfer Neurodegeneration Consortium’s early success, the Belfer family recently made an additional $20 million gift to advance the consortium’s goals for the next 10 years: to develop five new drugs to treat Alzheimer’s and related diseases, and for two of those drugs to show meaningful evidence of changing the course of the disease. The Belfer family’s $20 million gift will be matched through MD Anderson’s institutional fundraising efforts, bringing a total of $40 million to the consortium’s work.

The Belfer Neurodegeneration Consortium is currently running 12 projects targeting various aspects of Alzheimer’s, with one project already proceeding to a Phase I clinical trial. Efforts underway include the:

• Choline trial, which is testing whether a safe dietary intervention can reduce the risk of dementia in carriers of the APOE4 gene.
• DLK project, designed to develop a neuroprotective therapy for Alzheimer’s, which was awarded $20 million from the State of Texas to be developed also as a treatment for cancer patients who experience nerve damage due to chemotherapy.
• RIPK1 project, which aims to prevent microglial inflammation in the brain during neurodegeneration and could also prevent brain inflammation following radiation therapy.
• PU.1 project, which has identified PU.1 as a genetic risk factor not only for Alzheimer’s disease but also for leukemia.
• MS4A project, which targets the MS4A4A and MS4A6A genes for the prevention of dementia. These genes have also been shown to play a role in brain cancer.

The consortium hopes these projects will contribute to a multi-pronged approach for treating Alzheimer’s and neurodegenerative diseases at an earlier stage, ideally halting the disease’s progress before patients begin experiencing cognitive impairment.

“We are confident our goals are achievable,” Ray says. “The key elements for success are in place — a powerful research model, a winning collaborative team and a robust translational pipeline, all in the right place at the right time.”

Make a gift to support the Belfer Neurodegeneration Consortium.

The University of Texas MD Anderson Cancer Center and CureVac N.V. today announced a co-development and licensing agreement to develop novel mRNA-based cancer vaccines.

The collaboration creates strong synergies between CureVac’s unique end-to-end capabilities for cancer antigen discovery, mRNA design, and manufacturing and MD Anderson’s expertise in cancer antigen discovery and validation, translational drug development, and clinical research. The collaboration will focus on the development of differentiated cancer vaccine candidates in selected hematological and solid tumor indications with high unmet medical need.

"We look forward to collaborating with the team at MD Anderson to push the boundaries of mRNA technology and develop impactful therapeutic options for patients in need," said Alexander Zehnder, M.D., chief executive officer of CureVac. “In combining our respective expertise, we believe we can go further and faster to develop novel, off-the-shelf, mRNA-based cancer vaccines that have the potential to significantly improve patient outcomes.”

Both parties will contribute to the identification of differentiated cancer antigens based on whole genome sequencing combined with long- and short-read RNA sequencing and cutting-edge bioinformatics. Joint preclinical validation of the highest-quality cancer antigens will be supported by Sachet Shukla, Ph.D., assistant professor of Hematopoietic Biology and Malignancy and director of the department’s cancer vaccine program, and by MD Anderson’s ECLIPSE (Evolution of Cancer, Leukemia, and Immunity Post Stem cEll transplant) platform, part of the institution’s Therapeutics Discovery division.

“We are excited for cancer vaccines to potentially emerge as an essential therapeutic tool in the future,” Shukla said. “This collaboration with CureVac is an important milestone in our efforts and brings together complementary strengths toward our goal of developing transformative vaccines for cancer.”

Following selection of the most promising clinical-lead vaccine candidates and completion of Investigational New Drug (IND) approvals, MD Anderson will be responsible for conducting initial Phase I/II studies in appropriate clinical indications.

“Our ECLIPSE team uses proprietary high-throughput technology to identify and validate immune targets, and we are driven to advance impactful immunotherapies with the potential to transform the lives of patients with cancer,” said Jeffrey Molldrem, M.D., chair of Hematopoietic Biology and Malignancy and leader of the ECLIPSE platform at MD Anderson. “Together with CureVac, we hope to embrace this exciting area of drug discovery and development in pursuit of mRNA vaccines that will address significant unmet medical need.”

Under the terms of the collaboration agreement, CureVac and MD Anderson will jointly contribute to and support development of those programs designated to move forward. CureVac has worldwide exclusive rights to late-stage development, commercialization, or partnering of the cancer vaccine candidates. MD Anderson is eligible for certain downstream payments based on potential future commercialization.