The causes of Alzheimer's, Parkinson's, and
other debilitating neurological diseases are unknown,
but researchers at WVU believe a cure is on the horizon.
Ernest Villafranca's young chil- dren, newly transplanted from California, had never seen snow until two days after Christmas 2001, when Morgantown received its first real snowfall of the season. Meanwhile, their father—who in October became the executive director and CEO of the Blanchette Rockefeller Neurosciences Institute (BRNI) at WVU—is busy adapting to his own set of changes and to the biggest challenge of his professional life.
BRNI is the only research center in the world dedicated to the study of human memory. It was established in 1999 by U.S. Senator Jay Rockefeller and named in honor of his mother, a vital and accomplished woman afflicted by Alzheimer's disease in her final years.
BRNI's
mission is to pursue scientific research focused on practical
solutions (including prevention, diagnosis, treatment, and cure)
to neurological, psychiatric, and other cognitive disorders affecting
the human brain. First in line, as far as Villafranca and other
BRNI leaders are concerned, is Alzheimer's.
"It's a huge challenge, but I truly believe that this disease can be conquered," says Villafranca, a Ph.D. chemist who most recently headed discovery and pre-clinical development programs on Alzheimer's drugs for the pharmaceutical giant Pfizer.
BRNI got off the ground in 2000 with commitments from WVU for $10 million and $20 million from Neurologic, a pharmaceutical company which has a licensing agreement with the institute. A board of directors, with Senator Rockefeller as its founding chairman, and a scientific advisory board including two Nobel laureates and other renowned scientists, are working together to lead the institute.
Daniel Alkon, M.D., an internationally recognized authority in memory research, joined BRNI in 2000 as its scientific director. Prior to that, Alkon was the medical director of the National Institute of Neurological Disease and Stroke at the National Institutes of Health, where he served as chief of the Laboratory of Adaptive Systems. [See "Telling the Stories of Cells," Summer 2000.]
"We are extremely fortunate to have a scientist of Dr. Alkon's caliber to head up our research efforts," says Villafranca. "He is truly a brilliant man."
BRNI is a collaborative effort between WVU and Johns Hopkins University in Maryland, and research is underway at both universities. A new building planned for the institute on the WVU campus should be ready in 2004.
Villafranca says BRNI is very different from other neuroscience research centers in its mission and focus: "We plan to focus squarely on the major diseases of supreme urgency. First among these is Alzheimer's disease. There has been a great deal of basic research on the brain, but none of it has led to effective treatments for this terrible disease, which affects 25 million people worldwide and four million Americans. We plan to focus on research that will lead to effective treatments as soon as possible, and we will not stop until a cure is found."
To accomplish this goal, Villafranca says, BRNI will focus on what he calls "translational science," aimed at making discoveries with practical applications that will help patients. "Translational science bridges the gap between basic and clinical research," he explains. "This kind of research has been generally undersupported. The majority of government funding for biomedical research goes to basic research, and the development of treatments has been left to private industry. BRNI will help bring basic and clinical research together."
Something else different about BRNI is the way technology is shared among its researchers, says Villafranca, who admits that his industry background influences his thinking about how to get things done. "Instead of each researcher having only his or her own lab geared toward his or her specialty, which is traditionally how things are done in an academic setting, we are developing multidisciplinary technology departments to which all researchers will have access. We are setting up a dynamic organization in which the goals of the project will determine the allocation of people and resources. The focus is on identifying bottlenecks and working together to achieve results."
In addition to organizing resources to facilitate more effective internal collaboration, BRNI's leaders also are working to build what Villafranca refers to as a "global alliance network" in neuroscience research and development.
"We are developing important relationships with other neuroscience centers, with the pharmaceutical industry, and with other academic centers," he explains. "Traditionally, academic researchers worldwide are fairly isolated from each other and from clinical researchers who will translate their work into practical applications. Each group of scientists has its own laboratories and is working on its own projects, but they are not necessarily collaborating with others working on related questions. We want to build a network that can truly work together to achieve our common goals."
Villafranca says that one reason why medical science has been slow to develop treatments for many neurological disorders, particularly Alzheimer's, is that the underlying mechanisms causing the diseases are poorly understood. Animal models used to study many other diseases are not very helpful because most animals used for research—such as mice, rats, and gerbils—do not get these diseases. Transgenic animals, genetically engineered to get certain diseases so scientists can study them, are available but are very imperfect at this time.
"Therefore, one thing we are working on is developing better models for Alzheimer's disease so we can study it more closely, learn much more about the underlying causes, and use the animals to test our treatment strategies," Villafranca explains. "That is how diseases are conquered."
Recent research discoveries have yielded promising results, especially in relation to the genetic form of Alzheimer's, which shows up earlier in life than the sporadic form.
"We have learned that the processing of the amyloid protein, one component of the plaques found in the brains of people with Alzheimer's, is affected in people with the genetic form of the disease," Villafranca says, "and so there is a lot of research focused in that area."
Other current research includes a new diagnostic method for Alzheimer's, currently in clinical trials. The next major priorities for the institute, after Alzheimer's, are stroke and other neurodegenerative diseases.
BRNI currently employs about 20 scientists, but plans to expand that number to a hundred over the next two years. Its leaders are working to build the institute's endowment to support the planned personnel expansion and construction of the new building.
"It's going to take a substantial investment of resources to beat these diseases," Villafranca says. "But I'm confident that the initial support we have obtained will help us raise the rest of what is needed."
In addition to its great potential for finding treatments and cures for neurological diseases, BRNI is bound to have a major, positive impact on the economy of the state and region, Villafranca believes. "Once we build a critical mass of biotech activity here," he says, "I have no doubt that more biotechnology businesses will spring up.
When you bring people who have knowledge and ideas together, and give them access to the resources of the institute and the University, and the experience of companies like Mylan Pharmaceuticals, the potential for economic growth and development is huge." When he was approached about the BRNI position, Villafranca wasn't sure he wanted to make the leap from private industry to academic research. "But Senator Rockefeller and others convinced me that this job is not about ivory-tower research. It is about delivering results. It is about finding a cure. I couldn't turn down that challenge. I couldn't turn down the opportunity to contribute to something so important. And I truly believe we will succeed."
A Family's Loving Memory Inspires Hope
By Susan Case
When
Jay Rockefeller came to West Virginia in 1964, he brought with
him an idealism and commitment to public service instilled by
his family—especially by his mother, Blanchette Ferry Hooker
Rockefeller. She was an active volunteer and supporter of organizations
dedicated to education, the arts, and human services in New York,
and she raised her children to view helping others as an important
responsibility.
After his graduation from Harvard, Jay Rockefeller went to work
for the Peace Corps, but it was not until he came to West Virginia
at the age of 27 that he found his new home and calling. Working
with the residents of the small town of Emmons, he helped build
a community center, a library, and a park.
Rockefeller's experiences in Emmons launched his public service
career in West Virginia. The people of the state have elected
him to the House of Delegates, as Secretary of State, to two
terms as governor, and to three terms in the U.S. Senate. In
the Senate, Rockefeller has been an advocate for human needs,
including jobs, schools, and benefits for veterans, children,
senior citizens, and families. He is well known for his leadership
on health-care issues.
In the early 1980s, Blanchette Rockefeller was diagnosed with
Alzheimer's disease. The disease causes the slow, unstoppable
decline of everything that makes a person who he or she is: memory,
judgment, the ability to communicate, and, finally, physical
functioning. The slowness of the disease's progression means
that, for a long time, its victims are excruciatingly aware of
everything they are losing.
Families of victims can do little but provide custodial care
for their loved ones, who slowly turn into people they no longer
recognize, and who eventually can no longer recognize family
members or communicate with them.
When Senator Rockefeller speaks of his mother, the pain caused
to the entire family by her decline and death is evident. "My
mother's decline was agonizing," he says, "a painful
and slow eight years of watching the glow in her eyes fade, and
one of the brightest, most disciplined minds I've ever known
recede slowly into darkness."
Medical science has had little help to offer Alzheimer's victims
and their families. Although the 1990s saw so much basic brain
research that it was dubbed the "decade of the brain,"
research has yet to translate into effective prevention or treatment
strategies for Alzheimer's, Parkinson's, stroke, or many other
neurological disorders.
Blanchette Rockefeller died in 1992. To honor her memory, and
to help the many millions of other Alzheimer's victims worldwide,
Jay Rockefeller established the Blanchette Rockefeller Neurosciences
Institute in 1999.
In December, Rockefeller joined with other Rockefeller family
members—including his wife Sharon, his sisters Sandra Ferry,
Hope Aldrich, and Alida Messinger, and his uncles David Rockefeller
Sr. and Laurance Rockefeller—to donate $15 million to the
institute. Senator Rockefeller hopes that the gift will go a
long way toward making Alzheimer's a thing of the past.
"The human brain is such an extraordinary thing," he
says. "When diseased or unbalanced, it can bring confusion
and untold sorrow. But when healthy, free, and educated, it can
achieve miracles. It can bring love and compassion and hope into
our lives. And, with our help, it can find a cure for Alzheimer's
and Parkinson's, treatments for stroke and depression, the keys
to unlock the doors to understanding and preventing debilitating
disease. Together, we have created an institution that bears
my mother's name. And together, working through the institute,
we can create a legacy that would make her proud."