ALS RESEARCH ROUNDUP

High-Dose Tamoxifen May Prolong Survival

Neurologist Benjamin Brooks, who directs the MDA/ALS Center at the University of Wisconsin-Madison, presented results of a trial of tamoxifen, a drug approved for the treatment of breast cancer, at a meeting of the American Academy of Neurology in April. The trial was supported in part by MDA.

In a two-year study of 60 people with ALS who took varying dosages of tamoxifen, which changes the way the body responds to the female hormone estrogen, Brooks and colleagues found that participants who took more than 20 milligrams a day had a better survival rate than those who took fewer than 10 milligrams a day.

Benjamin Brooks

After two years, 27 out of 37 (73 percent) of the participants in the high-dose tamoxifen group had survived, while only 11 of 23 (48 percent) of those in the low-dose groups were still living.

There was no difference among the various dosage groups on measures of muscle strength, respiratory capacity, activities of daily living or functional abilities.

Brooks cautioned that a longer trial would be necessary to demonstrate with certainty that there’s a survival benefit to taking tamoxifen at the higher doses.

He’s planning further studies to investigate the effects of tamoxifen and also recommends that the metabolic products of tamoxifen be investigated.

IGF1 With Exercise Improves Survival, Function in Mice

Combining treatment with insulin-like growth factor 1 (IGF1) with a moderate exercise program proved to be of more benefit to mice with ALS than either treatment alone.

Brian Kaspar at Columbus (Ohio) Children’s Research Institute, and colleagues, studied mice with a genetic form of ALS, giving some of the mice injections of IGF1 genes into their leg and rib muscles. Other mice received no IGF1, while some were exposed to a running wheel, for two, six or 12 hours per day.

The researchers analyzed almost every possible combination of these groups, finding that treatment with IGF1 in combination with at least some running time each day brought the best results with respect to prolongation of motor (movement-related) function, number of remaining nerve cells, and survival time.

In their publication in the May issue of Annals of Neurology, the investigators say they realize that these results may appear to contradict other studies showing that athletes have a higher risk of developing ALS, and that high-intensity endurance exercise (treadmill running) hastens functional decline and death in male — but not female — ALS-affected mice. But, they say, the intensity, type and duration of exercise may be factors in determining its benefit and risk.

Researchers Block SOD1 Protein in ALS Mice

Timothy Miller at the University of California-San Diego, and colleagues, have shown that treatment with an “RNA silencing” compound can counteract abnormal SOD1 protein molecules that cause ALS, and that, in mice, it can be delivered to the spinal cord via an injection into muscle tissue.

The investigators, who published their results in the May issue of Annals of Neurology, used an adeno-associated virus (AAV) to package the silencer. (AAV is commonly used in gene transfer experiments targeting muscle cells and is considered relatively safe for human use.)

They found that the compound reached spinal cord nerve cells, reduced levels of the abnormal SOD1 protein, and allowed the mice to maintain strength in a treated leg.

RNA is the “final draft” of genetic instructions for protein manufacturing, and various strategies to keep it from leading to abnormal proteins are now being tried. Two European groups have recently conducted similar experiments. (See “Researchers Target SOD-1 Linked ALS,” May.)

Probing Nogo, High and Low

French study has found that production of various forms of a protein called nogo could provide insight into tissue degeneration in ALS. In 2000, Yale researchers identified nogo as a protein that blocks fiber regeneration after injury in the brain and spinal cord.

Natasa Jokic at Louis Pasteur University in Strasbourg, and colleagues, studied muscle biopsy samples from 15 people with ALS and found that levels of two types of nogo, nogo-A and nogo-B, were higher than levels of a third form, nogo-C. In adults without ALS, nogo-A and nogo-B are lower than nogo-C levels. In this study, the higher nogo-A and -B levels correlated with ALS disease severity.

The authors, who published their results in the April issue of Annals of Neurology, speculate that this reversal of predominance of nogo types in ALS may represent a return to an “embryonic-like” pattern of nogo production in ALS-affected muscle cells.

The researchers suggest that nogo levels could be used to monitor disease progression and response to investigational drugs.

Celgene Tries Thalidomide

Thalidomide, a drug notorious for causing serious birth defects in babies when their mothers took it during pregnancy in the 1960s, is now approved in the United States for limited use. Research has shown that one of its effects is reduction of levels of TNF-alpha, a protein involved in inflammation that’s been implicated in ALS.

The trial, sponsored by Celgene, makers of Thalomid brand thalidomide, will sponsor a study of 24 men and women with ALS who are between 18 and 80, have had ALS for five years or less, have mild to moderate levels of disability, and meet many other study criteria. Both sexes must use contraception or abstain from sexual contact, and participants must comply with stringent measures to monitor thalidomide usage and prevent fetal exposure to the drug.

For details, contact Linda Kingman at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., at (603) 650-8939, or linda.s.kingman@hitchcock.org.

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Are You Prepared for an Emergency?

by Margaret Wahl

You hope it won’t happen, but sometimes it does: an emergency. Here’s one couple’s experience and recommendations. Only their names have been changed, at their request.

It happened to the Pratts, a couple from New Jersey, a few months ago.

Joseph, 48, an art director at an advertising firm, learned he had ALS a year and a half ago, but his weakness had progressed quickly, and he was no longer working. His wife, Susan, a school librarian, felt comfortable leaving him home alone for certain periods of time, but it was clear more help would soon be needed.

Joseph, who had always been slim, was having a lot of trouble eating and had lost some 20 pounds since his diagnosis. And he was getting short of breath more often.

“The breathing became an issue,” Susan says. “We had seen Dr. Gordon [the MDA/ALS Center co-director at Columbia University in New York], and we were in the process of purchasing a BiPAP.”

Then one March afternoon, things suddenly became worse.

“That day he tried to take naps. He was very tired, but he couldn’t take a nap, even on his side, because of the shortness of breath,” Susan recalls. “Prior to that he had had these episodes, but he would recover his ability to breathe.”

This time he didn’t recover. “He was very uncomfortable, doing shallow, quick breathing, and we said, “This doesn’t seem right; maybe we should call 911.”

Off to the ER

The paramedics came quickly but couldn’t relieve Joseph’s distress and recommended going to a hospital 20 minutes away. While they got Joseph into an ambulance, Susan had only a few minutes to gather a few things, call her sister to take care of the Pratts’ 8-year-old son, Jimmy, and follow the ambulance to the ER.

There, Susan handed the ER doctor the phone number of neurologist Paul Gordon, but when the doctor called, Gordon wasn’t available. Fortunately, another neurologist covering for him got on the phone and suggested to the ER staff what tests should be ordered.

The couple were in the ER for six hours while various tests were conducted. Joseph’s carbon dioxide levels were found to be too high, and the doctors started him on a BiPAP.

When things worsened, they recommended hospitalization, intubated him (put a tube down his throat), and put him on a ventilator.

“They didn’t do the trach for about four days,” Susan says. “They said it could wait a few days, but if we didn’t [eventually] have a trach and vent, he would die.

“So the decision was made that weekend to go ahead with that, and also with a feeding tube.

“We had known about the use of these devices; Dr. Gordon had explained them. But we weren’t sure whether we wanted to go for them, and we had put those thoughts aside. We wound up having to get them anyway. It wasn’t planned.”

Fortunately, Joseph was able to make his wishes known in this emergency. “It was sort of in crisis mode, which was not a good thing,” Susan recalls. “But he told me, ‘I want to live,’ and he knew that if he didn’t have the trach done, eventually, he would die.”

Joseph is now in another facility, where doctors are trying without success to wean him from the ventilator. Susan is trying to figure out either how she can pay for around-the-clock care for her husband at home or whether he’ll go to a nursing home, which their insurance would cover for only a short time.

In retrospect, Susan says, things didn’t go as badly as they might have — but they could have gone better.

Advance Advice

Here’s her advice to caregivers:

“We didn’t do much talking about interventions,” Susan says. “They suggested that we think about a tracheostomy three months prior to the ER visit. But you don’t want to deal with it. You have ten thousand other things to do.

“It was very difficult, because his needs had been increasing over the last couple of months, so that I barely had time to scratch my nose. We never talked about it enough.”

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All Choked Up

by Diane Huberty

Editor’s Note: Diane Huberty, 57, of Fort Wayne, Ind., is a former neurology head nurse/instructor who has had ALS for 20 years. She writes frequently about tips for living with ALS.

It’s not uncommon in ALS for something unexpectedly and abruptly to aggravate your airway and throw you into a choking fit. I know from personal experience that these choking, gagging, gasping spells are physically exhausting, frustrating and upsetting for both the choker and the caregiver.

The actions to take for choking depend on the type of choking spell you’re having. For example:

The Heimlich Choke: A large piece of food completely blocks the airway. You can’t speak or cough. This is an emergency! It requires the Heimlich maneuver, either by a caregiver or self-administered, to force the blockage up and out. If not successful in two tries, call 911 and continue trying the Heimlich while waiting for help.

Prevention is the key here. Take care to monitor the consistency of your food. Cut everything into small pieces and take smaller mouthfuls. Bread and melted cheese are especially likely to form large “plugs.” Alcohol, talking or other distractions while eating increase the risk of choking.

Recommended Heimlich position for a seated person; be sure to put the wheelchair’s brakes on.

The Damn-Near Heimlich Choke: A pill or bit of food sticks in your throat. After a moment you can breathe but with a scary “heeee” sound.


Just as you start getting a little air in, you start coughing and/or gagging again. Over and over.

You can feel the darn thing stuck in your throat teetering between sliding up and making you gag and sliding down and making you cough. Scary, exhausting, but you can get a breath in between coughing spells.

The Heimlich or assisted cough technique may help. Focus on getting the obstruction upand out, not down the throat, because of the danger that it will lodge more firmly or go into the lungs. Therefore, avoid back whacking!

Talk with your clinic team about techniques appropriate for you and your caregiver’s strength. People with even minimal swallowing problems should never eat when home alone.

If you choke almost every time you eat and mealtimes are a dreaded experience, it’s time to get evaluated for a feeding tube. Besides the physical stress of a choking attack, the real danger of suffocation and the loss of calories due to fear of eating, choking can lead to aspiration, in which food or pills go into the lungs and cause life-threatening pneumonia.

The Foodless Sneaky Choke: You’re just sitting there minding your own business or even snoozing when suddenly you’re coughing and choking. A simple swallow of saliva goes awry and sends your larynx (vocal cords) into a spasm that closes off your airway. This is called a laryngospasm and isn’t uncommon in ALS. You fight to inhale but nothing happens. You can’t take a breath, can’t call for help, and panic crashes over you.

Recommended hand position for Heimlich maneuver

After an eternity, you finally suck in a thin, wheezing, tiny “eeee” breath. Slowly the spasm eases. The only thing I’ve found that helps me through these is the hard-learned lesson that they’re intense but short-lived. You’re not really choking, you can get some air, and the spasm will ease in just a moment or two.

Common causes of laryngospasm in ALS are liquid or saliva that went the wrong way into the larnyx, acid reflux disease, smoke, strong smells, emotion, alcohol, cold or rapid bursts of air, and even spicy foods.

Some techniques that may help ease the spasm include:

Caregivers can help by giving calm reassurance, gentle back rubbing (not whacking) and other support in riding out the spasm.

The Phlegm From Hell Choke: You try to clear your throat. Hrrrmph. Hrrrrrrrrmph. No good. Over and over you try to break up and cough out the thick clog in the back of your throat until you’re worn out and gasping.

My treatment is to take a dose of papaya juice or expectorant (guaifenesin, available over the counter) to thin the secretions. Then I lie down (BiPAP on) and have my caregiver do an assisted cough or use a cough assist machine. By lying down, I don’t have to fight gravity to bring the mucus up. Staying well hydrated can help keep secretions thinner.

The Nonchoke Sticker: A pill or bit of tortilla chip sticks on the way down and sits there feeling like a thorn in your throat. This little sucker can hurt for a day or more. After taking a small sip to make sure I can still swallow, I try taking the longest drink I can. Sometimes this repeated swallowing does the trick.

Advice to Caregivers: In any choking situation, fake being calm and quickly go through a list of possible actions. Ask, “Do you need a Heimlich? Assisted cough? A drink? Cough medicine? Suction?”

As with any aspect of ALS, always discuss choking concerns with your doctor. It’s good to practice the Heimlich and assisted cough techniques before you need to use them. For more information on these techniques, contact your local MDA/ALS center or MDA clinic.

MDA Medical Director Valerie Cwik and Senior Writer Christina Medvescek contributed to this article.

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