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We certainly have a lot to report in
this summer’s newsletter! The clinical trial
of high dose CoQ10 in ALS (called the
QALS study), directed by my colleague, Dr.
Petra Kaufmann, began stage 2 only 4
months ago. Already 80 patients have
been enrolled, recruited from ALS Centers
throughout the United States. It took only
several weeks, which was way ahead of the
enrollment goal. Next spring, after 9
months, we will get the final results. This
study has a unique design consisting of two
stages: the first stage determined which
dose of CoQ10 is better than the other.
The second stage studies the effects of the
dose chosen after completion of stage 1.
The higher dose was chosen based on a
side effect profile. The final statistical
analyses will be made in patients combined
from the first and second stages of the
study for a total of 185 patients.
Throughout the United States, 18 centers
are participating in this QALS study with
the entire operation being conducted at
Columbia University. The statistical
Principal Investigator, Dr. Seamus
Thompson, the data manager, Richard
Buchsbaum, and the statistical coordintor,
Anita Tierney, come from the Mailman
School of Public Heath. The clinical study
coordinator, Alexandra I. Barsdorf, is from
our ALS Center. I received praise from my
colleagues at other centers for how well
and professionally the QALS study has
been conducted. Obviously, our Columbia
site has enrolled the largest number of
patients and we certainly appreciate your
participation. We will have the results
next spring.
In other news, the minocycline
clinical trial, operated by the Western ALS
Study Group and headed by Dr. Paul
Gordon, the Associate Director of our ALS
Center, was completed.
We regret that the
patients who were on
minocycline declined
more when measured by
the ALS functional rating scale than those
who were on an inactive drug. Obviously,
this is a blow, but certainly it will not stop
us from continuing to try other potential
medications. As everyone knows, well
designed and placebo controlled clinical
trials are the only way to find an effective
medication for ALS. This will only
strengthen our efforts to identify a second
and more effective medication than
riluzole.
Another study is already two thirds
complete: a genetic-environmental
epidemiology study funded by the
Muscular Dystrophy Association. I very
much appreciate the help of everyone who
participated in this study. It involves
either a face-to-face or telephone interview
and a blood draw for DNA analyses in the
future. We guarantee the confidentiality of
all participating individuals. The study
interviewer asks questions about family
medical history, residential history,
occupational history, as well as any
military experience or physical activities.
We also ask the same questions of their
family members as the controls, which
include siblings or spouses of siblings. This
is a unique study to identify genetic and
environmental/lifestyle factors possibly
associated with ALS. We have just been
notified that the Muscular Dystrophy
Association will fund the next study
investigating the relationship between
oxidative stressors and ALS. The grant will
enable us to initiate the first step of an ambitious and detailed epidemiological study involving the
New York Metropolitan area. A larger grant would be
neceessary to conduct such a study. The overall goal of this
study is to determine if genetic, environmental, lifestyle, or
psychological factors are in any way associated with
oxidative stress in ALS. In this study, we will compare the
paitents with three different controls: the spouse (sharing
current environment), the siblings (sharing early life
environment), and community controls (sharing
environment in the same location).
There is another topic that many people may be
interested in: the usefulness of exercise in ALS. When I
was at the Cleveland Clinic (it feels like ages ago), I started
a project investigating the effects of strengthening
(resistance) exercises in patients with ALS with my former
research physical therapist, Vanina Del Bello-Haas, PhD.
After I moved to Columbia we asked other investigators at
Washington University to join us. The results were just
reported in the June 5th issue of Neurology. The study
indicates that strengthening or resistance exercise
improves ALS function based on the ALS functional rating
scale and quality of life scale, and in fact, leg muscle
weakness declined less in the exercise group. Although
such a study must be confirmed by another study involving
a larger number of patients, we believe that the right
amount of strengthening exercises, if they are done
carefully and properly, maybe be beneficial to those who
have early ALS. Now, we are almost ready to embark on a
very different type of bicycle exercise study. We are
interested in investigating the physiological and
biochemical effects of ramp incremental cycle aerobic
exercise in patients with ALS. This exercise is in fact
identical to a routine cardiac exercise stress test. We hope
to begin enrolling in a pilot study this summer.
We have a number of current on-going projects. In
this newsletter, Jackie Montes writes about skin biopsy
protocol for developing stem cells using a nuclear transfer
technique through a Harvard and Columbia collaboration.
A project studying cognitive function in patients with ALS,
directed by Dr. Gordon, is now half way done. An NIHfunded
nutritional study to investigate how much energy
patients actually consume and expend has completed
enrollment. The study will be completed in the next
several months. This is a multi-center study to identify
the natural history of the nutritional status in patients
with ALS.
In other important news, our ALS Center and
Motor Neuron Centers are closely collaborating to
develop a new project to determine the cause of ALS.
I regret to report that Dr. Paul Gordon, who
done outstanding work as the Associate Director of our
Center, is leaving us at the end of August to study
cognitive impairment in patients with ALS at a world
renowned hospital, the Hôpital de la Salpêtrière in Paris.
We will miss him. To take over his work, we of course
have Dr. Petra Kaufmann and will have Dr. Jinsy
Andrews, who was our ALS fellow between 2005 and
2006 and completed a year as an EMG fellow. Dr.
Andrews will join us as an instructor. She was the
recipient of a highly prestigious award from the MDA,
the MDA David A. Garner ALS Research Fellowship.
This award will enable her to study the methods of
clinical trials in ALS and neuromuscular diseases at the
Mailman School of Public Health, Columbia University
and she will work with me in studying oxidative stress
ALS. Our new ALS fellow this year is Dr. Amy Chen.
She received an MD and PhD from the College of
Physicians and Surgeons, Columbia University. While
completing her PhD, she studied with Dr. Eric Kandel,
Nobel laureate. She completed her neurology residency
at Albert Einstein College of Medicine. We also have
research fellow Dr. Woo Kyung Kim from Hallym
Medical School in Seoul, Korea. We continue to put
maximum effort into our patient care and clinical
research.
I hope everyone has a wonderful summer!
Hiroshi Mitsumoto, MD
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