Physician-scientist Frank M. Longo, MD, PhD, has been named the inaugural winner of the Alzheimer’s Drug Discovery Foundation’s (ADDF) Melvin R. Goodes Prize for Excellence in Alzheimer’s Drug Discovery, the first prize to specifically recognize researchers working in novel and promising areas of Alzheimer’s drug discovery. Dr. Longo is Professor and Chairman of the Department of Neurology and Neurological Sciences at Stanford University School of Medicine and founder and Chairman of biopharmaceutical firm PharmatrophiX.
“It is fitting that Dr. Longo is the recipient of the first Melvin R. Goodes Prize, as his pioneering research has significant potential to result in successful disease-modifying treatments for Alzheimer’s within the next few years,” said Howard Fillit, MD, Founding Executive Director and Chief Scientific Officer of the ADDF. “By establishing this prize, we seek to celebrate the research of scientists such as Dr. Longo, whose drug discovery work often goes unrecognized, and provide them with a monetary award, so that they can continue taking bold chances in pursuit of novel and effective treatments.”
Dr. Longo and colleagues developed an innovative approach to identifying and developing small, orally available drugs that mimic the function of normal brain proteins (i.e., neurotrophins) that protect nerve cells (neurons). These molecules counter a type of brain signaling that destroys nerve cells and their connections in neurodegenerative diseases. Preclinical studies showed that these compounds can tackle multiple mechanisms believed to be involved in the development and progression of Alzheimer’s—protecting neurons from the toxic effects of beta-amyloid and inhibiting formation of toxic forms of tau. One of these experimental medications is now in clinical trials. Dr. Longo will use his $150,000 Goodes Prize to help advance clinical development of a second promising Alzheimer’s drug candidate.
“My colleagues and I are thrilled to receive the Goodes Prize, and appreciate the significance of the ADDF recognizing novel approaches and encouraging drug discovery research,” said Dr. Longo.
The ADDF was among the initial funders of Dr. Longo’s drug discovery work and provided a number of additional grants, including funding to support the creation of PharmatrophiX and its clinical development program. “Our approach was a highly risky one, with no good precedent in the field of neuroscience,” said Dr. Longo. “Our success in obtaining NIH funding for this work required that we first demonstrate success in early stages. ADDF support has been critical to our progress, both at the beginning and at several key points.”
Dr. Longo pioneered the development of small molecules that target key mechanisms controlling the health and functional status of neurons and their vital synapses (the structures responsible for transmitting signals between neurons). Neurotrophins are naturally occurring and highly potent brain proteins that are responsible for the development, growth and survival of neurons. These molecules attach to specific neurotrophin receptors on the cell surface to promote signaling mechanisms that help prevent, or in some cases even reverse, the loss of synaptic connections that occurs in Alzheimer’s disease, thereby preventing loss of cognitive function. Small molecules developed by Dr. Longo’s team prevent degenerative signaling patterns more effectively than naturally occurring neurotrophin proteins. In pre-clinical studies, these compounds prevented cognitive decline and the destruction of neurites, outgrowths of neurons that are critical to establishing brain circuits. Dr. Longo founded PharmatrophiX in 2005, while at the University of North Carolina, to manage the commercial development of these compounds and move the most promising into clinical trials. ADDF was a founding investor in the company. Anne Longo serves as CEO, managing finance and operations.
Dr. Longo’s drug discovery work has been done in collaboration with Dr. Stephen Massa (University of California, San Francisco), who created innovative software approaches to more effectively screen potential drug candidates. This led to the development of the first small-molecule, drug-type compounds that can mimic key parts of growth factor proteins and prevent or reverse degenerative signaling within neurons. The first of these compounds (LM11A-31), which targets the P75 neurotrophin receptor, completed a Phase I clinical trial in 2013–2014 without significant adverse events. It is now undergoing additional safety testing and is expected to begin a Phase IIa trial in Alzheimer’s patients in 2016. A second compound that targets a different neurotrophin receptor (TrkB) is in preclinical development, and Dr. Longo has developed additional P75-targeting compounds.
These compounds are able to penetrate the blood brain barrier—a characteristic critical for treating brain disorders. They also bind to individual neurotrophin receptors, rather than binding to multiple receptors as occurs in the case of the neurotrophin proteins, which when tested caused multiple side effects, some of them not tolerable to patients. Preclinical Alzheimer’s studies show that the P75 compound LM11A-31 can inhibit the progression of degeneration and cognitive loss when given in mild to moderate stages; and when administered in late stages, can reverse the loss of synaptic connections.
The Melvin R. Goodes Prize, which is named in honor of the courage, legacy and research advocacy of Mr. Goodes, former Warner-Lambert CEO and Chairman and honorary member of the ADDF’s Board of Governors, was created thanks to the generosity of Mr. Goodes and his wife, Nancy, who is also on the ADDF’s Board of Governors. The Goodes Family Foundation has made a commitment of $750,000 to fund the Goodes Prizes for 10 years, and the ADDF has matched that contribution.
Each year, the Goodes Prizes will be awarded to a professionally active researcher in academia or industry who has pursued novel research and made a significant and lasting impact in Alzheimer’s drug discovery. A Selection Committee that includes leaders in the field nominates candidates for consideration and chooses a winner based on past achievements and proposed research in need of funding.