Chemotherapy for cancer is often life saving, but it also causes a debilitating syndrome of impaired cognition characterized by deficits in attention, concentration, information processing speed, multitasking and memory. As a result, many cancer survivors find themselves unable to return to work or function in their lives as they had before their cancer therapy. These cognitive deficits, colloquially known as "chemobrain" or "chemofog," are long-lasting and sometimes irreversible. For example, breast cancer survivors treated with chemotherapy suffer from cognitive disability even 20 years later.
These cognitive problems occur because chemotherapy damages the neural stem and precursor cells necessary for the health of the brain's infrastructure, called white matter. We have discovered a powerful way to recruit the stem/precursor cells required for white matter repair that depends on an interaction between the electrical cells of the brain, neurons, and these white matter stem/precursor cells. In this project, we will determine the key molecules responsible for the regenerative influence of neurons on these white matter stem cells and will develop that molecule (or molecules) into a drug to treat chemotherapy-induced cognitive dysfunction. If successful, this will result in the first effective treatment for a disease that affects at least a million cancer survivors in California.
Approximately 100,000 Californians are diagnosed with cancer each year, and the majority of these people require chemotherapy. While cancer chemotherapy is often life saving, it also causes a debilitating neurocognitive syndrome characterized by impaired attention, concentration, information processing speed, multitasking and memory. As a result, many cancer survivors find themselves unable to return to work or function in their lives as they had before their cancer therapy. These cognitive deficits, colloquially known as "chemobrain" or "chemofog" are long-lasting; for example, cognitive deficits have been demonstrated in breast cancer survivors treated with chemotherapy even 20 years later. With increasing cancer survival rates, the number of people living with cognitive disability from chemotherapy is growing and includes well over a million Californians. Presently, there is no known therapy for chemotherapy-induced cognitive decline, and physicians can only offer symptomatic treatment with medications such as psychostimulants.
The underlying cause of "chemobrain" is damage to neural stem and precursor cell populations. The proposed project may result in an effective regenerative strategy to restore damaged neural precursor cell populations and ameliorate or cure the cognitive syndrome caused by chemotherapy. The benefit to California in terms of improved quality of life for cancer survivors and restored occupational productivity would be immeasurable.
This proposal aims to address impaired cognition that can be caused by chemotherapy, a condition sometimes referred to as “chemobrain.” Patients who develop this condition can experience deficits in attention, concentration, information processing speed, multitasking, and memory. The applicant has developed a method of recruiting the stem cells involved in brain white matter repair. These studies will determine key molecules that affect white matter stem cells and their ability to promote regeneration. This work may yield drug development candidates to treat chemotherapy-induced cognitive dysfunction in cancer survivors.
- The rationale is logical and compelling and addresses a significant clinical problem.
- The approach is highly innovative and uses cutting-edge technology.
- Good preliminary data were provided for some aspects of the project. Some reviewers thought that including in vivo data showing quantifiable cognitive changes would have made the proposal stronger.
- While white-matter damage is a logical target, possible damage to other regions of the brain, which may be involved in some symptoms of the disorder, was not discussed.
- The PI is an outstanding young investigator with a strong track record of success.
- Reviewers felt that the PI is clearly committed to a career in neurobiology and stem cell research has a strong likelihood of becoming a significant force in these fields.
- Excellent mentors were identified who have appropriate expertise for the research project and experience facilitating the career development of other physician-scientists.
- The institution has provided abundant and appropriate resources and support for the investigator.
- The institution provides in excellent environment for both accomplishing the proposed research and the PI’s career development.
- The application is highly responsive to the RFA in its use of hESC-derived neural cells and its focus on translation.
- Since there is not yet a development candidate, it was felt that it would be difficult to secure funding for this work through a federal research grant.