America first became aware of amyotrophic lateral sclerosis (ALS) in a major way back in 1939, when New York Yankees champ Lou Gehrig told fans that he had it. Three years later the movie Pride of the Yankees immortalized the moment when the athlete (played on film by actor Gary Cooper) announced to a hushed stadium audience—as well as millions listening via radio at home—that he was hanging up his cleats.

ALS soon became known by the moniker of Lou Gehrig’s disease. Progressive, disabling and usually fatal, it is characterized by a wasting away of certain nerve cells of the brain and spinal column, a process that eventually shuts down functions such as walking, eating and ultimately breathing.

At the University of California, Irvine (UCI), two men are on the frontlines of ALS research: Augie Nieto, who has the disease and chairs the ALS Therapy Development Institute (ALS TDI), and Dr. Tahseen Mozaffar, who once treated him for the disease. The two recently secured $36 million in funding to study what causes ALS and what might potentially treat it.

The pair also researched other neuromuscular diseases, such as muscular dystrophy (MD), so when ABILITY Magazine’s editor-in-chief Chet Cooper went to interview Nieto and Mozaffar, he took along ABILITY’s long-time graphic designer Steve Mikailoglu, who lived with MD for 27 years. (Steve died recently, before he could see this interview published).

Chet Cooper: Augie, you were featured on TV recently.

Augie Nieto: I was on the Today show, where they did a series on real-life heroes. They profiled four people, and I happened to be one of the four. They talked with me about the irony of my being a fitness guy in my former life, and now, in my current one, living with a disease that takes away your muscles. They also looked at what I’m doing to change the way people look at ALS research.

Steve Mikailoglu: I understand that part of that change is through a foundation?

Nieto: I don’t have my own foundation. My business network advised me to work through an existing foundation, which was funding research for ALS at the highest level, and then to go to them with five requirements. So when I went to the Muscular Dystrophy Association (MDA), my number one requirement was that 100 percent of the money raised went to research. Number two: No money could be spent without my approval. Number three: Any money I raised was incremental to the ALS budget they had, and they already had the largest research program for ALS, so they couldn’t take the money and switch it with somebody else’s. Number four: Any relationship I brought to the MDA would be mine forever. And number five—probably the best one of all—there would be no overhead. With a lot of charities, they’ll charge you for corporate office staff, and I didn’t want that.

Fortunately, the MDA was agreeable to the terms, so I now have a contract with them. It’s been an incredible tool to raise money, because I give my donors, who I view as ambassadors, a copy of the contract so they know where the money’s going—they know it’s going to research, they know it’s incremental, and they know that I must approve everything. So this has become the most efficient way for the ALS community to funnel money.

Cooper: You’re lucky, because even though MDA is a non-profit organization, they still have a large overhead. So you’re able to piggyback onto their operation without any cost.

Nieto: What was even more encouraging was to see what Warren Buffett did a year later. He duplicated what I did. He said, “Look, I have $34 billion. Do I want to start my own foundation, or do I want to leverage what Bill and Melinda Gates are doing?” He did the latter. So to me, it was a validation of our strategy.

Mikailoglu: How did the relationship between you and Dr. Mozaffar develop?

Mozaffar: Augie first came to see me in August 2005. I was the fifth neurologist he had seen for a diagnosis of ALS. He had seen some of the best, at institutions ranging from Johns Hopkins in Baltimore to California Pacific. He and I have worked together closely since then, not only as physician and patient, but also on some of the endeavors he’s undertaken, for which I’ve served as an advisor. Over time, we’ve developed a very trusting relationship. He takes my advice; I take his advice. We each play the role of confidant.

Cooper: So Augie, he gives you medical advice—what advice do you give in return?

Nieto: (laughs) I give him some fitness advice—but no investment advice so far!

Cooper: Do you still find yourself involved in the fitness community, teaching the public about exercise and diet?

Nieto: I’m still the chairman of a company called Octane Fitness, which makes the best elliptical product on the market. I’ve donated a lot of equipment for rehab to UCI and other institutions to really share what I believe.

Cooper: And that is?

Nieto: I can sum it up in one word—move.

(laughter)

Cooper: Hold it, we’ve got to write that down... Move.

Nieto: (smiles) Yes, move.

Mikailoglu: Well, what kind of movement would you like to see in the research on ALS?

Nieto: One issue I found as I went around the country meeting with doctors was most of them were researching their own hypotheses about what would slow down or stop ALS. But they weren’t really interested in the fundamentals. When I look at the problem with ALS, I frame it in four questions: What causes it? How do you slow it down? How do you stop it? How do you reverse the damage it does? I found was there was little focus on what caused it. If you make an analogy to erecting a building, everybody was interested in being on the 53rd floor, without first establishing a foundation.

So over the next 24 months I intend to put together the largest single assault on ALS. We’re committing $18 million to the ALS Therapy Development Institute (ALS TDI) in Cambridge, Massachusetts, which is matching that money. So that means $36 million will go to research that will help us find answers to those four critical questions.

Mikailoglu: What research are you doing in Southern California?

Mozaffar: We do mainly clinical research and trials on ALS, including work both with experimental medications and with meds already on the market that have never been tried for this particular indication. In addition, we belong to other consortia, so we participate in research with other groups. The problem with ALS is that it’s a relatively uncommon disease. There aren’t that many patients with it, so the big pharmaceutical industry has little interest in it at this point. Therefore, to be able to attract funding for some of these research projects, ALS researchers and ALS physicians have to band together.

So there’s the Western ALS group and the Northeastern ALS group and the Great Lakes ALS group. We meet to discuss ideas. In one of the projects we worked on—which would not have been possible without Augie’s influence—we basically examined every single gene in the human system. We were looking for a specific signature—specific markers that might be different in ALS patients.

Cooper: As a scientist working in this area, what are some of the problems you’ve seen over the years in ALS research?

Mozaffar: Augie referred to one of them—in the ALS community, researchers tend to have their own religion, as far as which particular hypothesis or scientific idea they want to pursue, although those topics may or may not have any relevance as far as treatment is concerned.

For example, about five percent of ALS tends to be inherited (runs in families). A lot of the work so far has been driven by this familial form of ALS, including the only animal model we have of the disease. So all clinical trials we have done to date—and all the medications we’ve tested—have been based on that single animal model, which may or may not be relevant to the other 95 percent of the ALS population. Fortunately, we now have the molecular technology to look across the spectrum of both familial and non-familial ALS in a study of 1,000 patients.

Mikailoglu: You studied 1,000 ALS patients?

Nieto: Actually it was 1,251. There was such excitement in the 14 different sites that people were driving in just to participate. As a business guy, I thought, “How do you truly get big pharmaceutical companies to go after the treatment of a disease?” And it’s really simple—you give them intellectual property protection. If you’re really going to do the fundamentals and figure out what causes the disease, you’re going to be able to patent all the way through the pathways and then license those patents to big pharma to give them protection.

If you’re able to find a single drug that is applicable in the U.S., where there are currently 30,000 ALS patients, you can claim what’s called orphan drug status. That’s when fewer than 200,000 people are affected by a disease, and it allows us to take advantage of the protections put into place by the 1982 Orphan Drug Act passed by Congress. Those protections include seven years of market exclusivity, no restrictions on pricing, and fast track approval by the Food & Drug Administration. With orphan status, a drug treatment could command $150,000 per patient per year. And then if you extend that person’s life from five years to 10 years, then all of a sudden you have an economic model that serves as an incentive for big pharma to develop a product. So our approach is twofold: to extend the life of an ALS patient, and to own all the intellectual property (protect it, license it, generate additional income from the royalty that will fund additional research).

Cooper: What did you find in your study of the 1,251 patients?

Mozaffar: There were about 14 unique genes found. The most exciting part was that some of them were completely novel genes—genes we had not previously thought about. So I think we’re definitely getting new clues. Now the idea is to take it to the next step. Let’s focus on these 14 genes—these 14 pathways—and see if any of them are useful in finding a treatment.

Studies from scientific and academic institutions have always been very hypothesis driven. And traditionally, if you did something out of the box as we did, it would be frowned upon. But I think times have changed. Now people are thinking, “Let’s do a shortcut approach.” The technology is available, so rather than coming up with a prejudged hypothesis, the thinking is, “Let’s do a completely blind search and see what we find.”... continued in ABILITY Magazine

ABILITY Magazine
Articles in the Frankenstein issue; Emme Aronson—Couples Fighting Depression; Car Wars—May the Force be Green and a Q&A with Toyota; Humor Therapy; Pet Peeves; All the World's a Stage, But How Do I Get a Ticket to the Show—Disability Legal Rights Center; Iraq Vets—Healing on the Slopes; Virginia Tech—Lessions to be Learned; Chop Chop—Try a Raw Food Diet; ABILITY's Crossword Puzzle; Events and Conferences...subscribe