Hypothesis

Imagine an injection that reverses Alzheimer’s, a nasal spray that stops autism, or a pill preventing the debilitation of certain genetic syndromes. It’s not wishful thinking; it’s the work going on in Cristina Alberini’s lab at the NYU Center for Neural Science.
    Alberini has studied the biological molecular mechanisms of memory and learning for three decades. Early in her career, she says, brain science was so underdeveloped that—despite her fascination with the biological basis of human behavior—she got discouraged and decided to study immunology. But “the brain kept calling me back,” she says, and in the early ’90s, she returned to it.
    Driven by the belief that “we are what we learn and what we remember,” Alberini began determining how exactly, on a molecular level, the brain stores and retrieves long-term memories. She started with sea snails. “There was literally nothing known, so using very simple systems was the way to go,” she says. Mice and rats followed, with which Alberini and her team focused on insulin-like growth factor 2 (IGF2), a tiny protein with huge potential for how a host of brain disorders are treated.
    “In the most basic terms,” says Alberini, “IGF2 is a potent memory enhancer.” The peptide, involved with both learning and long-term memory storage, exists naturally in the human brain. Alberini and her team discovered that by increasing levels of IGF2 in rats immediately after teaching them something new, the rats learned faster and memories of what they learned were more persistent.
    That discovery made big news back in 2011, but for Alberini, creating superpowered minds is less interesting than repairing damaged brains. “It’s great to be able to enhance normal memory—everyone wants to be able to work less and learn more,” she says. “But the most exciting use for IGF2 would be in treating memory and cognitive disorders.” She and her collaborators are looking into applications for Alzheimer’s, Parkinson’s, and autism, with Alberini’s current focus being on Angelman syndrome, a rare genetic disorder that causes intellectual and physical disabilities as well as seizures.
    The results in the lab have been extremely promising. Rats treated with IGF2 saw significant alleviation of age-related memory loss; in mice, IGF2 reversed many deficits associated with Alzheimer’s. Benefits go beyond memory improvement: Alberini saw a reversal of cognitive and motor symptoms, as well as a drop in repetitive behaviors, all associated with Angelman syndrome. What these diseases have in common, she explains, is an overaccumulation of proteins in neurons, preventing the brain from functioning properly. IGF2 is like the brain’s cleanup crew, and because it mops up the whole range of proteins—not just a specific protein built up by a specific disease—it has the potential to treat a wide range of disorders.
    Still, considerable research is needed before clinical testing—and Alberini is currently looking for investors to fund the necessary studies. “I don’t really know how long this is going to take,” she says, when asked about getting IGF2 to patients. “First we want to be safe, but I hope we aren’t going to delay too much. Because if it works, it’s going to be really great.” That, to be sure, is an understatement.
    In the meantime, another NYU researcher is working to improve the lives of those currently suffering from dementia. Abraham “Ab” Brody (CAS ’02), associate director of NYU’s Hartford Institute for Geriatric Nursing, recently received a $6.1 million grant from the National Institute on Aging to fund studies of his Aliviado program, which educates caregivers about how best to address the harrowing and often difficult-to-manage symptoms of the disease.
    “Aliviado means ‘relief’ in both Spanish and Portuguese, and this sums up the program’s goal: relief for the patient and caregiver, and an overall improvement in quality of life,” says Brody, who is also an associate professor at the Rory Meyers College of Nursing.
    It was while treating dementia patients as a nurse practitioner that Brody saw the need for the program. “I realized there was a real lack of understanding of how to work through and understand pain and behavioral symptoms,” he says. “I would talk with clinicians from home health and hospice agencies when I was [treating patients], and they were frustrated because they didn’t have the knowledge they needed.”
    Currently, Aliviado is working with home health and hospice agencies, and Brody hopes to soon expand the program to nursing homes. The major goal, he says, is helping clinicians understand the causes of patients pushing back, screaming out, or otherwise resisting care so that patients’ underlying needs can be met—rather than overmedicating them or lashing out in frustration themselves. “Unlike in my role as a nurse practitioner at the medical center, I’m not touching patients directly,” says Brody, “but it’s a force multiplier. The idea that I can help thousands of clinicians and therefore potentially hundreds of thousands of patients over my lifetime to get better care, that’s both my vision and my drive.”

Insulin-like growth factor 2 is a tiny protein with huge potential for how a host of brain disorders are treated.