Neurodegeneration dream team

CAMBRIDGE, Mass.—A $25 million gift from the Robert A. andRenee E. Belfer Family Foundation has brought the talents of three powerhouseneurodegeneration research institutions together to create the transformativeNeurodegeneration Consortium that looks to advance the study and care ofAlzheimer's and other diseases.

The consortium brings together the Picower Institute ofMemory and Learning at MIT, the University of Texas MD Anderson Cancer Centerand Baylor College of Medicine. Each institution will bring its own strengthsto bear in a robust and multifaceted partnership that will strive toward betterunderstanding the underlying instigators of Alzheimer's disease.

The focus of the research will extend beyond the amyloidhypothesis that attracts most of the focus in the field. The amyloid hypothesissuggests that the buildup of amyloid beta-peptide in the brain is a primaryinfluence in the neurodegeneration associated with Alzheimer's disease.

"There appear to be multiple mechanisms at work inAlzheimer's disease … there are co-conspirators beyond amyloids in the brain,"says Dr. Ronald DePinho, president of MD Anderson.

Recent research at MIT, among other institutions, hassuggested that neurodegeneration, cancer and other diseases associated withaging are intimately linked. Age itself appears to be the most important riskfactor, leading researchers to believe that understanding the "circuitry" ofaging at the molecular level holds the key to preserving patient health andenhancing quality of life in an aging population.

The consortium will attempt to leverage its members'multidimensional backgrounds to adopt an unbiased view of the problem, hittinga "reset button" for Alzheimer's research and attempting to apply genomic andcomputational biological technologies to identify new therapeutic points ofattack.

Picower Institute Director Li-Huei Tsai is a prominentneuroscientist specializing in Alzheimer's research, and will serve as the leadMIT investigator. The team of investigators includes Lynda Chin, DePinho,Giulio Draetta, Ming-Kuei Jang and Philip Jones of MD Anderson; Juan Botas,Joanna Jankowsky and Hui Zheng of the Baylor College of Medicine; and Hugo Bellenand Huda Zoghbi of the Howard Hughes Medical Institute and the Jan and DanDuncan Neurological Research Institute at Texas Children's Hospital, BaylorCollege of Medicine.

The Picower Institute and Baylor College will be the leadingforces behind the underpinning science and pathway development. Once targetsare identified, the infrastructure for drug development will be done at MDAnderson. MD Anderson's drug development team, which possesses 200 years ofcombined experience, is tasked with converting the research into viableclinical drug candidates.

"This consortium combines talented people and real drugdevelopment capabilities that can be converted into proof of concept," saysDePinho.

Early-stage drug development has already begun on one promisingnew target for myeloma and brain, breast and other cancers.

The consortium's benefactor, Belfer, has supported cancerresearch in the past, and when he became interested in neurodegeneration, hestarted by asking trusted experts what the field needed to make progress. Theseconversations led him to assembling something of a "dream team" of scientistswith expertise in Alzheimer's disease, autism, cancer and other illnesses in arobust cross-fertilization of scientific disciplines. The investigators chosenfor the consortium include individuals capable not just of making scientificdiscoveries, but also instigating drug development.

The $25 million gift serves as a launching point for theconsortium's preliminary work. However, the gift is contingent on theconsortium partners securing matching donations—another $25 million in fundingby Jan. 1, 2016. About $6.5 million of this funding has already been raised.

DePinho is optimistic that the consortium's preliminary datawill help to secure matching funds and reignite interest in neurodegenerationamong players in the pharmaceutical industry.

"Pharma has moved away from neurodegeneration because ofsome of the failures of past research," he says. "We hope to re-engage pharmaand take new drugs to trial. The consortium being funded by a philanthropicgift allows us to be more maverick and take risks."

"We're not repeating or competing against anything anyoneelse is doing," says Dr. Huda Zoghbi, director of the Duncan NeurologicalResearch Institute.

On a more somber note, DePinho recounts the impetus for theconsortium's work.

"Incidence of Alzheimer's disease rises dramatically afterage 60. There will be 1.2 billion people over age 60 in the world by 2025—westand to see a several-fold increase in a very costly disease," he says. "Weneed to address this problem with a higher level of urgency because we're on acollision course with a health crisis."