‘Drug Cocktail’ Shown Doubly Effective Against ALS in Mice
by Dan Stimson A new MDA-funded study shows that when mice with ALS are given both
creatine and minocycline, they develop symptoms of the disease later
and survive longer than mice given either drug alone.
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Robert Friedlander
Marshall Matthews in his 1914 Stutz Bearcat |
Helping Others
Matthews, 56, lives in Woodside, Calif., and has two children, ages
16 and 20. The owner of Matthews-Carlsen Body Works in Palo Alto for
25 years, he remains active in his business, though he's no longer able
to work full-time.
"He still goes in when he can, and he has a few projects of his
own, but it isn't like it was before ALS came along," Nancy says.
"He keeps a lot of his collection there, and I think he enjoys
just being around the people and keeping involved."
Matthews also attends clinic at the Forbes Norris MDA/ALS Center at
California Pacific Medical Center in San Francisco.
"We're lucky, in that we have good insurance so Marshall's ALS
won't wipe us out financially," Nancy explains. "But when
you see what this disease costs people who aren't as fortunate as we
are, it's just amazing."
That's why they established the Marshall Matthews Family Fund, to help
raise awareness — and money — specifically to help support
the ALS center's services program.
"We saw that most of the money being raised goes to research, and
obviously we support that," she relates. "We just felt that
this was where we could really make a difference."
And what a difference!
Raising Friends and Funds
In September, the Matthewses hosted a Classic Car Garden Party at their
home, an event that Nancy Matthews describes as a "friend raiser."
Attendees heard speakers from the MDA/ALS Center discuss ALS research
and treatment, enjoyed refreshments and toured Marshall's car collection.
With the help of family friend Chris Carter and his employees at Motion
Pro (a Redwood City, Calif., manufacturer of motorcycle parts where
Matthews' 16-year-old son works part-time), the event brought in voluntary
contributions totaling close to $200,000.
"It was wonderful," Nancy says simply. "We have so many
terrific friends, and since Marshall's diagnosis, we've had friends
we hadn't heard from in a long time contact us to see if they could
help. It"s been very good for Marshall, especially."
Quest Looks at Talking with Technology
|
Valerie Pingle (left), an occupational therapist, and MDA client Pati
Milewski work with speech-generating devices at a January meeting of
MDA's Olympia, Wash., ALS support group. In the March-April issue of
Quest, MDA's bimonthly magazine, Milewski and others share their views
on everything from etiquette to the challenges of using an augmentative
communication device.
Watch for the issue to arrive in your mail in late February.
ALS Research Roundup
Scientists from the National Institutes of Health in Bethesda, Md.,
and Johns Hopkins University in Baltimore have shown for the first time
that stem cells from adult bone marrow can become neurons in the human
brain.
They found evidence of that transformation by examining postmortem brain
tissue from patients who had received bone marrow transplants for leukemia
or immune system deficiencies.
The stem cells in adult bone marrow give rise mostly to blood cells
and immune cells, but recent studies on mice suggest that they can sometimes
migrate into the brain and form neurons.
To test the idea in humans, the NIH-Hopkins team examined brain tissue
from four female patients who had received bone marrow transplants from
male donors. By looking for cells that had a Y chromosome (present only
in male cells) and proteins found exclusively in neurons, they discovered
that multiple brain regions in each patient contained a small fraction
of marrow-derived neurons (two to five for every 10,000 neurons counted).
Many other brain cells had Y chromosomes but lacked neuronal proteins,
and were probably neuronal support cells called glia.
The findings, published online in January by the Proceedings of the
National Academy of Sciences, offer hope that bone marrow transplantation
might replace, or at least repair, the neurons damaged by ALS. Stanley
Appel, director of the Ronny and Linda Finger MDA/ALS Center at Baylor
College of Medicine in Houston, is testing the procedure in an MDA-funded
clinical trial.
Study of Genetic, Environmental Risks Needs Your Help
Researchers at Northwestern University in Chicago and Massachusetts
General Hospital/Harvard University in Boston are continuing their joint
study of genetic and environmental risk factors in ALS.
The study, which is funded by the National Institutes of Health, needs
blood samples from people with ALS who have no family history of the
disease ("sporadic" ALS) and from certain relatives and spouses.
Blood samples can be drawn locally, and all expenses associated with
the drawing and shipping will be absorbed by the investigators.
For information about the Chicago trial, contact Nailah Siddique at
(312) 503-2712 or nsiddique@northwestern.edu;
or Lisa Dellefave at (312) 503-0154
or l-dellefave@northwestern.
edu. In Boston, contact Diane McKenna-Yasek at (617)
726-5750 or dmckennayasek@partners.org;
or Kathryn Canniff at (617) 726-5750 or kcanniff@partners.org.
Both centers are also conducting separate studies of people with familial
ALS, those in whom ALS has occurred in more than one family member.
These studies have similar requirements to those of the sporadic ALS
study, involving blood sample analysis and questionnaires. The contact
information is the same as above.
Researchers Probe Marijuana in ALS
Greg Carter, co-director of the MDA/ALS Center at the University of Washington in Seattle, in conjunction with researchers at the University of California, Davis, has surveyed people with ALS who have used marijuana and related compounds. Carter and colleagues designed an anonymous, online questionnaire for which access ended in late January.
 Greg Carter |
In November, conferees attending the 13th International Symposium on
ALS/MND in Australia learned about a small study that showed a marijuana-derived
compound called dronabinol (brand name Marinol) may improve sleep,
appetite and muscle tightness in people with ALS. (See December
2002.)
Experts say marijuana-related compounds deserve further study for their
possible use in symptom relief and perhaps some neuroprotective properties.
Pentoxifylline
Under Study in Europe
ExonHit Therapeutics, a French pharmaceutical firm based in Paris with
an office in Gaithersburg, Md., is sponsoring a study of a drug known
as pentoxifylline. The trial will evaluate the safety and effectiveness
of the drug, which ExonHit refers to as EHT 0201
.
All participants will take riluzole, an approved medication for ALS;
but some will also take pentoxifylline, while others will take a placebo.
The trial is double-blind and randomized, which means that neither participants
nor investigators will know who is on the placebo and who is getting
the experimental drug. Participants will be randomly assigned to one
group or the other.
The investigators will study about 400 participants with ALS at 12 European
centers. U.S. patients aren't being enrolled at this time but may be
eligible in the future.
ExonHit identified pentoxifylline (brand name Trental) as a potential
ALS treatment candidate through a patented screening technique called
DATAS, which the company recently developed to detect altered genetic
sequences that could lead to ALS-related chemical changes.
Using the DATAS technique, ExonHit learned that mice with ALS are more
likely than mice without ALS to possess a genetic variation that leads
to an excess of a compound called phosphodiesterase
4B.
Since, among its other actions, pentoxifylline is known to block phosphodiesterases,
the researchers have speculated that it might reduce the excess supply
of the 4B compound and perhaps help in ALS.
Pentoxifylline also blocks a substance called TNF-alpha, known
to promote inflammation, another potential culprit in ALS.
ExonHit says pentoxifylline has a good safety record in the treatment
of arterial obstruction and crosses into the nervous system from the
bloodstream. In the United States, pentoxifylline is on the market for
circulatory conditions in which it is desirable to reduce the viscosity
("stickiness") of the blood.
For more information, see www.exonhit.com;
or call the U.S. office of ExonHit at (240) 683-7070.
READERS RESPOND — Is ALS a Disability
or a Fatal Disease?
 Cheryl Carter New |
An article called "ALS — A Disability
or a Fatal Disease?" by Cheryl Carter New in the January issue
generated several responses from readers. Here's a selection of comments.
I can't tell you how much I agree with everything you said in your
article. I've had ALS for 25 years and I have always considered myself
disabled, not dying. It infuriates me that people with other neurological
diseases are encouraged to adapt to their limitations while people with
ALS are told to go home and wait to die.
The expense issue equally infuriates me. I'm old enough (56) to remember
polio patients. Those who fought to survive by going on iron lungs were
applauded, not told they were selfish. I've had a very enjoyable life
and plan to do so for many more years.
Thanks again.
Meredith Dubin
Tustin, Calif.
What a beautifully written article! Why does the health care community
treat this disease as a "death sentence?" My mom [Connie Rodgers]
cried when the doctor told her [she had ALS], and the doctors spoke
to the family about "terminal issues."
So now that I have been brainwashed into thinking "terminal,"
how does one change their point of view, and attempt to present this
to someone with ALS? My mom is not positive, and I feel like she is
giving up. She says she is just "tired" and doesn't have the
will to go on.
Denise Kay Jones
Mount Airy, Md.
I respectfully disagree with most of your opinions. You state, "ALS
affects voluntary muscles — not the critical ones we need to live."
My wife lost her battle with ALS in 2002. ALS, unfortunately, attacks
all muscles — voluntary and involuntary. [Editor's note: ALS affects
skeletal muscle, some of which, such as the respiratory muscles, are
partly involuntary.]
My wife battled ALS with tremendous courage — positive and realistic
thinking.
ALS is a disease that continually destroys the body — hence the
term "fatal disease." I'm not trying to express gloom. I'm
just being realistic. ALS has a track record of being a fatal disease.
However, there are many, many, many exceptions to the rule.
In the near future, with God's help and medical research, this disease
will cease to be.
Ed Popiden
McKees Rocks, Pa.
Cheryl New presents the concerns very elegantly. Physicians and
other health care professionals involved in the care of people with
ALS need to read her article. People with ALS still, today, often receive
a message of hopelessness when they are told of their diagnosis. They
are told that they have a fatal disease and frequently they are not
offered the options that enable survival and quality of life.
Each person with ALS must make their own choices based on their goals
and preferences; however, this must be based on good information and
a positive approach from their physicians.
Edward Anthony Oppenheimer, M.D.
Pulmonary Medicine
University of California, Los Angeles
I wanted to both congratulate and thank the newsletter staff for
this [January] issue. I am an ALS patient in Memphis. All of the articles
were excellent, most positive and encouraging to me and my family.
The article by Cheryl Carter New gave me a lot to think about. She is
so right that you have to learn to live with ALS and make the most of
the situation.
Like Ms. New, there are a lot of things I can no longer do, but
there are many more things that I can do that are rewarding and enjoyable.
Why not continue to do them? After all, I really don't miss cutting
the lawn anyway. There is no need to dwell on things we can no longer
do.
The Caribbean cruise we recently took and the symphony we attended on
Sunday were great fun. Things like expense and burden mean nothing to
my family who are now doing lots for me after me doing so much for them
for so many years. I have concluded that they need me and don't care
that I can no longer walk. I have been through all the mental hurdles
that all patients must go through and have come out of it with such
a positive outlook. Talking to others with ALS, other caregivers, staff
at the local MDA clinic and reading positive articles like that by Ms.
New have all helped get me to where I am now.
Wayne Tichenor
Cordova, Tenn.
No one can tell a person with ALS when they are going to die. You can't
diagnose that. Mayo Clinic said my dad [with ALS] would be gone in a
year back in '99. They also said he'd need a tube within a month or
two of his diagnosis, too. He still eats without a tube.
Keri Adamy
Jenison, Mich.
I think it is up to that person who is dealing with such illnesses like
my mother and others with ALS. They have a lot of courage and stamina,
and I believe that God is also helping them and us caregivers to have
all the strength in us to continue in such a path of being survivalists.
As humans we are that, and we will continue to find a cure for this
challenging thing that is upon our loved ones.
Christina Makosiej
British Columbia
Miami Man Finds ‘Freedom Land’
Freedom Land, by Martin L. Marcus, 2003, 352
pages, $24.95. Forge Books (Tom Doherty Associates), available in bookstores,
www.tor.com/forge.html.
On Feb. 1, a new epic historical novel, Freedom Land,
was launched at the Books and Books store in Coral Gables, Fla. The
book is the first novel written by Martin L. Marcus of Miami, a man
who is described as a psychologist, screenwriter, thoroughbred horse
trainer, real estate developer, entrepreneur, and advocate for those
with physical disabilities.
Sadly, Marcus, who had had ALS since 1997, was unable to attend the
launch of Freedom Land — he passed away
in December. His longtime partner, muse and first editor, Carol Durban,
attended the launch in his place.
"He did live to see his novel become published," Durban says.
"And I know he was really looking forward to getting out and meeting
some of his readers."
. |
Freedom Land tells the story of Florida's native
Seminoles, and their struggle for freedom during the Seminole wars of
1817 and 1832. It also tells of the many former African slaves who joined
the Seminoles' fight, and of Billy Powell, who married Seminole Chief
Micanopy's daughter and later became known as Chief Osceola.
Freedom Land is lovingly, painstakingly researched,
and features appearances by such historical figures as Andrew Jackson
and Zachary Taylor.
Changes Made in Medicare Payments
Medicare recipients with rare diseases who rely on receiving injectable
or intravenous orphan drugs through hospital outpatient clinics may
find their medications harder to get, now that Congress has allowed
a Medicare payment exception to expire.
The orphan drug "outlier" exception in the Medicare Hospital
Outpatient Prospective Payment System (HOPPS) expired Jan. 1.
This change doesn't yet affect people with ALS, as there are no Medicare-approved
injectable or intravenous drugs for the disease. But those with ALS
could be affected in the future, according to Diane Dorman, vice president
for public policy at the National Organization for Rare Disorders (NORD).
"Future treatments and possible cures may be inaccessible. For
example, promising protein and enzyme therapies for genetic diseases
are likely to be injectable and intravenous products," she said.
NORD is lobbying Congress to amend the Social Security Act to make the
orphan drug "outlier" exception permanent, and to ensure that
each orphan drug would be considered individually for payment.
ALS Community Protests Kelly AFB Findings
A flurry of criticism followed the recent verdict that there's apparently
no "ALS cluster" among workers at the former Kelly Air Force
Base in San Antonio, Texas (see "No
ALS 'Cluster'," December 2002.)
After results of the investigation were published in November in the
Journal of Occupational and Environmental Medicine, some professionals
and families in the ALS community expressed disappointment.
Most of the criticisms centered on two points: that the study didn't
include people living with ALS but only those who'd died of it; and
that the study excluded all military personnel who had worked on the
base, counting only civilians.
In defense of the study, investigators, including Carmel Armon, professor
of neurology at Loma Linda University in Loma Linda, Calif., said that
including military personnel would have weakened the study by including
too many people who'd spent a very short time at Kelly. The civilian
workers, he said, were there for much longer, and the biologic hypothesis
under which the investigators were working suggested that a long exposure
to any putative toxin would have been needed to cause ALS.
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Neurologist Merit Cudkowicz, an MDA research grantee at Massachusetts
General Hospital in Boston, who was also involved in the study, said
it would have been too difficult and therefore less accurate to study
people living with ALS. She said that would have required surveying
all those living with ALS in the populations being compared to the Kelly
group, which would have included the state of Texas (one comparison
group) and the whole United States (the other comparison group).
A neurologist who directs an MDA clinic and didn't want to be identified
expressed concern about the elimination of military personnel from the
study. He said the researchers couldn't have known in advance whether
the length of exposure to a possible toxin at Kelly AFB was more important
than the nature of the exposure. If military personnel and civilians
were exposed to different chemicals, the results of the study might
be inaccurate.
He also said that studying the number of ALS cases in existing populations
wouldn't necessarily have been hard to do and might have yielded more
information than just studying deaths from ALS.
Reducing Caregiver Stress May Help Loved One’s Depression
by Christina Medvescek
Depression is common among ALS patients at all stages of the disease
and becomes worse when the primary caregiver is overburdened, according
to a 2001 survey of 2,576 people with ALS.
The ALS Patient Care database is a large-scale "report card"
on how U.S. physicians treat ALS and how people with ALS experience
their illness and health care.
Some 43 percent of those surveyed described themselves as both depressed
and receiving treatment for depression. This figure is higher than the
national average for both stroke and cancer patients.
Depression was more common among women with ALS, and was present at
all levels of disability. Symptoms of depression include despair, numbness,
irritability, loss of enjoyment in favorite activities, sleep difficulties,
loss of appetite and giving up.
Three Phases of ALS
Linda Boynton de Sepulveda, a nurse-researcher who manages the MDA/ALS
Clinic and Research Center at the University of California at Los Angeles,
compiled the report. She notes that depression can be triggered by the
psychological readjustment required by each of the three phases of ALS.
Boynton de Sepulveda identifies these phases as diagnostic (when
people have disturbing symptoms and are chasing a diagnosis); palliative
care (when the steady loss of function can be overwhelming); and
terminal (when people confront fears of dying and spiritual or
existential concerns).
Linda Boynton de Sepulveda |
Caregivers Need Care, Too
Although past studies have shown that social support can help protect
chronically ill patients from depression, the ALS survey data yielded
a new perspective.
"Caregiver burden," which occurs when caregivers experience
poor health, financial worries and lack of help, had a negative influence
on the patient's coping skills at all levels of disability.
"Caregivers need to care for themselves," Boynton de Sepulveda
reported, suggesting medical checkups, respite care, caregiver support
groups, counseling and working with a case manager/social worker to
identify sources of income and assistance.
"By attending to the needs of the caregiver, both the patient and
the caregiver can reduce feelings of distress," she said.
Boynton de Sepulveda advised that depression is a serious risk in ALS
that should be recognized and managed with various strategies, including
medication.
The ALS Patient Care Database is a project of the ALS Clinical Assessment, Research and Education (CARE) Program. To learn more about ALS CARE, or to see the survey forms, go to www.umassmed.edu/outcomes/als or call (508) 856-2577.
Quality
of Life Relates to Fatigue, Depression
A small study conducted by Jau-Shin Lou and colleagues at Oregon Health
& Science University in Portland has found that quality of life
in ALS correlates more with energy levels and mental state than it does
with the specific degree of functional impairment in the disease or
the duration of the disease.
The investigators administered five questionnaires that measured physical
limitations, muscle strength, general quality of life, fatigue (general,
mental and physical), depression, and sleepiness to 25 people with ALS.
They published results in the Jan. 14 issue of the journal Neurology.
Those with ALS scored higher (more affected) than people without ALS
on measures of physical and general fatigue and had higher depression
scores. These, the researchers concluded, had a negative effect on quality
of life.
Disease severity didn't correlate with quality of life in ALS, and disease
duration contributed only marginally.
The researchers concluded that people with ALS who have excessive sleepiness
should be offered noninvasive ventilation. They suggested that drugs
to reduce sleepiness, such as modafinil (Provigil), be studied in ALS.
They also recommended trials testing antidepressants or psychosocial
intervention.
News
and Notes From MDA Online
If you haven't done so already, we hope you'll put http://www.als-mda.org
on your list of favorite Web sites. Not only is information on MDA's
ALS Division Web site updated frequently, the site also offers the opportunity
to interact electronically with others affected by ALS, and with some
of the leading clinical experts and researchers studying the disease.
Clinical-Research Conferences
The 2003 Clinical-Research Online Conference series is well under way,
hosted by MDA Director of Research Development Sharon Hesterlee and
MDA Senior Science Writer Dan Stimson.
And while topics range among the more than 40 neuromuscular diseases
in MDA's program, here are two sessions that those with ALS won't want
to miss:
On Feb. 19, Jerold Reynolds, respiratory therapist in the Neurology
Department at Ohio State University, will discuss respiration
and ventilation with neuromuscular diseases.
On March 5, Jeremy M. Shefner, M.D., Ph.D., director of the MDA/ALS
Research and Treatment Center at SUNY Upstate Medical University, will
field your questions on ALS research, covering both
clinical trials and mouse models used to study ALS.
MDA Clinical-Research chats run from 5:30 p.m. to 6:30 p.m. (all times
are EST). For more information, point your Web browser to http://www.mda.org/chat/calendar.html.
Two New Chats Debut
Support for family members and caregivers is the focus of two new weekly
chats:
The Spouse-Family Group is there for those who are
unable to attend evening support groups. Join "wendy5858"
every Monday from 1 p.m. to 1:30 p.m.
And caregivers can share everyday successes, frustrations and tips every
Tuesday from 6 p.m. to 8 p.m. with host "shelia-s" at Caregivers
Online.
For a full schedule of MDA chats, go to www.mda.org/chat/calendar.html
.
ALS
Caregiver Guide Available Online
The 2002 edition of MDA's When a Loved One Has ALS: A Caregiver's
Guide can now be seen online at www.als-mda.org/publications/alscare.
The 60-page guide covers topics including caring for the person with
ALS, caring for the caregiver, end-of-life issues and getting help.
There's an extensive, up-to-date listing of resources as well as information
about the programs in MDA's ALS Division.
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A print copy of the guide is available at local MDA offices, with one
copy free to each family with ALS registered with MDA. For others, copies
can be ordered at
www.mda.org/publications/puborder.aspx
or through MDA offices.