Celebrity with a purpose
19 Apr 2013

The Michael J. Fox Foundation for Parkinson’s Research aims to cure Parkinson’s disease

In 1998, actor Michael J. Fox, his television and movie career in full flight, made a dramatic announcement. He revealed that he had early-onset Parkinson’s disease (PD), first diagnosed seven years prior.

In 2000 Fox left full-time television work for a time, in part to focus on the new eponymous foundation he formed to seek a cure for PD. He was far from the first to use celebrity to gain attention for a serious disease, but Fox had far more ambitious goals than most. Yes, the Michael J. Fox Foundation (MJFF) would raise money for research, as all such foundations do. But it would also seek to change the whole disease research paradigm.

“MJFF is the model of how these things should work,” says The Jackson Laboratory’s Michael Sasner, Ph.D., who works directly with the foundation. “They come at it from both sides, the science side as well as the patient side. So while they raise a lot of money, from the start they’ve worked closely with both their own scientific staff and outside experts on how to leverage it wisely.”

Sasner is the associate director of bioinformatics and model development in Jackson’s Genetic Resource Science group. That means mostly that he works hard to make mice more effective for human disease research. And in the PD research area, MJFF has become a driving force in creating new pre-clinical models for the disease.

“Before 2010 mouse model development for PD wasn’t as effective as it could have been,” says Sasner. “There were IP (intellectual property) issues—for example, a promising disease model developed in an academic lab would not be available to a for-profit pharma company for drug development. MJFF is working to develop useful PD models and make them widely available.”


A new kind of disease foundation
PD is a neurodegenerative disease characterized by tremors and other movement problems. It’s a disease of aging that affects one in 100 Americans over age 60, but it manifests much earlier in some patients, such as Fox. PD’s symptoms arise from the loss of brain cells that produce dopamine, a brain chemical whose functions include coordinating movement, but the genetic and environmental contributors are not well understood. Current therapies, including drugs that replace or mimic dopamine’s function in the brain, do not slow disease progression, may lose effectiveness over time, and often cause significant side effects. There is no cure.

MJFF combines scientific attention to detail and efficiency with aggressive action. Their scientists and businesspeople are in-house, not external, collaborating to be at once pragmatic and forward thinking. Perhaps the best summary of their outlook is on their website, on a page titled “Our Promise.” Under the heading We are risk-takers and problem-solvers it says: “From inception, MJFF has invested in high-risk, high-reward research targets; an approach that in 10 short years has transformed the broader approach in the PD research field.”

How does this translate to research? “MJFF provides critical support for translational research, which lies in the huge gap that exists between basic research, largely funded by the NIH, and clinical trials, which are done by pharmas,” says Kuldip Dave, Ph.D., senior associate director of research programs at MJFF. “We also have a global view of PD research. We know the new targets and new approaches for PD therapy development, so we can identify the most promising projects and deploy funds quickly and responsibly.”


What JAX offers
One of PD’s challenges is that the disease offers few strong clues regarding its underlying genetics. In fact, it’s likely that different combinations of genetic variants and environmental factors contribute to susceptibility in most cases. It’s therefore not surprising that no one mouse strain has provided an ideal model of the human disease, and JAX is a vital partner as the search for better research tools continues.

“JAX is a non-profit and has tremendous genetics expertise, so it’s a good fit for us,” says Dave. “We started working with them to distribute our mouse models. Now all of our models end up at the JAX repository regardless of where they are generated. And they are doing a lot more, including the necessary genetic characterization and quality assurance, making sure all the animals have the genotype they should. JAX has become a one-stop shop for us.”

Sasner says JAX is just starting to work with a mouse model in which it can delete a gene that was identified to be a risk factor in humans but has yet to be characterized in a mouse. “It’s an unknown at this point,” he says. “For-profits wouldn’t take on a project like that. It’s where JAX’s unique place in the research world helps. We can contribute and get on the ground floor of a new kind of human disease model development.”


Looking forward
No one has any illusions that MJFF has an easy mission. Neurodegenerative diseases such as Parkinson’s—and also Alzheimer’s and ALS—have proven tremendously difficult to treat and, to this point, impossible to cure. Changing that reality will take bold thinking, a large amount of difficult work and continued optimism. As Fox himself says: “The cures we want aren’t going to fall from the sky. We have to get ladders and climb up and get them.”

It will also take collaborative efforts with wide-ranging constituencies—patients, doctors, pharma and biotech companies, researchers and unique partners like JAX.

“We are scaling up our ability to contribute to translational medicine using human genetic data,” says Sasner. “JAX has diverse strengths for developing new models for human disease, thoroughly characterizing and validating them, testing new compounds and more. The work takes a large team, but it’s all coordinated and overseen by an individual scientist here.”

“I speak with Mike Sasner pretty much weekly, and he contributes a lot to our overall model development strategy,” says Dave. “We work closely with JAX, and we see them as a partner in our PD research efforts.”