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 audienceas well as millions listening via radio
at homethat he was hanging up his cleats.
ALS soon became known by the moniker of Lou Gehrigs 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 Magazines editor-in-chief Chet Cooper
went to interview Nieto and Mozaffar, he took along ABILITYs 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 Im 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 dont 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 couldnt
take the money and switch it with somebody elses. Number four: Any
relationship I brought to the MDA would be mine forever. And number fiveprobably
the best one of allthere would be no overhead. With a lot of charities,
theyll charge you for corporate office staff, and I didnt
Fortunately, the MDA was agreeable to the terms, so I now have a contract
with them. Its 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 moneys goingthey know its going to research,
they know its incremental, and they know that I must approve everything.
So this has become the most efficient way for the ALS community to funnel
Cooper: Youre lucky, because even though MDA is a non-profit organization,
they still have a large overhead. So youre 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 hes undertaken, for which Ive
served as an advisor. Over time, weve 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 advicewhat advice do you
give in return?
Nieto: (laughs) I give him some fitness advicebut no investment
advice so far!
Cooper: Do you still find yourself involved in the fitness community,
teaching the public about exercise and diet?
Nieto: Im still the chairman of a company called Octane Fitness,
which makes the best elliptical product on the market. Ive 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 wordmove.
Cooper: Hold it, weve got to write that down... Move.
Nieto: (smiles) Yes, move.
Mikailoglu: Well, what kind of movement would you like to see in the research
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 werent 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
So over the next 24 months I intend to put together the largest single
assault on ALS. Were 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 its a relatively uncommon disease.
There arent 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 theres 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 onwhich would not have been possible without Augies
influencewe basically examined every single gene in the human system.
We were looking for a specific signaturespecific markers that might
be different in ALS patients.
Cooper: As a scientist working in this area, what are some of the problems
youve seen over the years in ALS research?
Mozaffar: Augie referred to one of themin 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 dateand all the medications weve
testedhave 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 its really simpleyou
give them intellectual property protection. If youre really going
to do the fundamentals and figure out what causes the disease, youre
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 youre able to find a single drug that is applicable in the U.S.,
where there are currently 30,000 ALS patients, you can claim whats
called orphan drug status. Thats 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 persons 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 genesgenes we had not
previously thought about. So I think were definitely getting new
clues. Now the idea is to take it to the next step. Lets focus on
these 14 genesthese 14 pathwaysand 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, Lets do a shortcut approach.
The technology is available, so rather than coming up with a prejudged
hypothesis, the thinking is, Lets do a completely blind search
and see what we find....
continued in ABILITY Magazine
Articles in the Frankenstein issue; Emme AronsonCouples
Fighting Depression; Car WarsMay 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 ShowDisability Legal Rights Center; Iraq
VetsHealing on the Slopes; Virginia TechLessions to be Learned;
Chop ChopTry a Raw Food Diet; ABILITY's Crossword Puzzle; Events