Research Serendipity

Philip Haydon, professor and chair of the Department of Neuroscience, discovered that to achieve great payoffs in business, an entrepreneur must be tenacious and have strong convictions. The Haydon laboratory studies how astrocytes regulate synaptic transmission and the role they play in disorders of the central nervous system. Astrocytes are glial cells found throughout the nervous system that were once thought to be merely structural. A serendipitous finding by Haydon—that astrocytes participate actively in neural transmission—led him to form the start-up company GliaCure.

Rethinking established roles

For most of the 20th century, neuroscience focused on the role of neurons in brain function. No one questioned whether glial cells played anything other than a supporting role. Perhaps this was because glia are electrically mute: the electrical recording and stimulation techniques that launched the discipline of neuroscience were deaf to glial cells.

Haydon and his colleagues began to question the role of glial cells when they confronted data that made no sense. Expecting to block the release of chemical transmitters, the Haydon lab killed off neurons in a sample of living brain tissue. The surprise was that some transmitters were released anyway. Haydon’s conclusion: glia, the only cells left living in the dish, must be releasing the same chemical transmitters as neurons.

This discovery, published in Nature in 1994, was the first evidence that glial cells modulated synaptic activity. Yet for a long time neurocentric scientists did not accept the idea that glia performed a role in modulation. Haydon ignored the skepticism and continued researching glial cells. The tenacity paid off, and Haydon along with others went on to identify how glia are active in the brain and how glial subtypes serve different functions. Today the study of glial cells is recognized as vital to our understanding of brain function. The success of Haydon’s research led to the formation, in 2011, of the start-up company GliaCure, with a mission to identify and target glia-based signaling pathways for the development of new therapies for neurological and neuropsychiatric disorders.

Building a start-up

In recent preclinical studies, the Haydon lab identified a novel glia-based target that is highly effective in reversing Alzheimer’s disease in mouse models. Haydon approached the Tufts technology transfer office to build a bridge for his discovery between academia and industry. Tufts tech transfer engaged a medicinal chemist to further the development of agonists to the glial target and hired a contract research organization to synthesize analogs.

Moving an idea from basic research into clinical study is becoming increasingly difficult. Because they lack the proof-of-principle data needed to attract industry partners, promising therapies often stall in their early stages. The funds Tufts provided for the analogs helped bridge this translational gap—also referred to as the “valley of death”—and increased the commercial potential of the Haydon group’s invention. As a result, Haydon was able to secure money from angel investors to found GliaCure. In January 2012, Tufts concluded a license agreement that will yield milestone payments from GliaCure and royalties on products.

“As a leading research university, Tufts has a unique opportunity to accelerate the development of early-stage technologies that could benefit the public,” says John Cosmopoulos, senior associate director, Tufts technology transfer office. “Providing proof-of-principle funding to Tufts investigators helps fulfill our mission and ensure that promising technologies reach their full potential.”

Says Philip Haydon, “I am very pleased with the expertise provided by the Tufts tech transfer office. Some of the most important treatments and medical technologies today originated from collaborations between academia and industry. The funding provided by Tufts helps ensure that breakthrough products are propelled from the lab to the commercial development stage.”

In founding GliaCure, Haydon partnered with Michael Szulczewski, co-founder of the imaging company Prairie Technologies. Their complementary skills from academia and industry will provide a solid base for GliaCure’s success. Completing the GliaCure board of directors is Walter Dewey, senior portfolio manager and principal of Reinhart Partners, a Mequon, Wisconsin—based investment advisory firm with $4 billion in assets under management.

Treating Alzheimer’s disease

GliaCure was formed to develop new therapies for conditions such as Alzheimer’s disease and epilepsy, sleep disorders, and a range of related psychiatric disorders. Working from the principle that there are many glia-based targets that existing drug discovery programs have overlooked, the GliaCure team has already identified new compounds geared toward treatments for Alzheimer’s disease. The company’s goal is not merely to arrest development of the symptoms of Alzheimer’s disease; it is also focused on therapies for preventing disease onset and reversing early cognitive decline.

There is a significant need for Alzheimer’s disease treatments. By 2050, the number of people with Alzheimer’s aged 65 and older is predicted to triple, from 5.2 million to up to 16 million. The cost of treatment is estimated at $1.1 trillion. Currently there are five FDA-approved drugs that temporarily slow the symptoms of Alzheimer’s disease, in about half the patients, for 6 to 12 months. There is currently no treatment that prevents the degenerative process.

An effective treatment that could be provided in the early stages of Alzheimer’s disease and would halt cognitive decline is especially needed. GliaCure is poised for success if its new compounds prove in clinical trials to reverse the degenerative process and prevent the onset of disease.