No Fear
Neither ALS nor deep, dark waters can slow down Frank Andrews

by Kathy Wechsler

A retired engineer, Frank Andrews of Katy, Texas, has never been the type of guy to just sit back and let life pass him by. Always wanting to give scuba diving a try, Andrews, 46, made his first dive 15 years ago. He quickly discovered that exploring the underwater world was in his blood, and he started diving with a group of friends from church.

Murky waters

After receiving a diagnosis of ALS in 2002, Andrews was determined to continue the sport, even if he needed to adapt and to accept help from friends.

A harness enables Andrews’ friends to hoist him in and out of the water, and tow ropes help him keep up.

As Andrews’ disease progressed, he started using a battery-powered underwater scuba scooter with a small propeller to help pull him through the water. In the last two years, though, Andrews, who now uses a power wheelchair, has had a personal dive assistant from the resort tow him through the water with a 10-foot rope.

Eight to 10 of Andrews’ friends usually go with him on the diving trips and assist him with putting on the scuba gear and with transfers. Andrews wears a harness underneath his diving vest so that three or four of his friends can grab the harness straps and hoist him back on the boat.

Underwater adventures

Since his diagnosis, Andrews has made seven scuba diving trips to the Cayman Islands, Bonaire and Roatan, off the coast of Honduras. Each trip consists of 14-18 dives, during which Andrews has the opportunity to see an array of tropical fish, sea turtles, and many other forms of underwater life.

The majority of his dives are 50 to 70 feet deep, but Andrews usually does one 120-foot dive per day.

When Andrews and friends went to Roatan last May, he had the opportunity to do a shark dive three to four miles offshore. It was a 75-foot dive to the bottom, and divers took along a bucket of dead fish. 

“The sharks start circling, and it’s pretty exciting. There are some big sharks, some eight to 10 feet long, and they’ll pass within arm’s reach of you,” says Andrews. “They’re wild sharks, but they’re kind of used to the divers and know that if they hang around they’ll get a free meal. Once you get used to it, it’s not quite as scary as it sounds.”

Night-diving is one of Andrews’ favorite things to do. Divers swim 50 to 60 feet underwater with lights.

“A lot of people think that’s even more scary than the sharks, swimming around 50 to 60 feet underwater in the dark,” he says. “I’ve just always enjoyed that type of thing.”

Underwater life is even more amazing at night. Andrews recalls seeing huge lobsters, octopi and crabs the size of basketballs.

Andrews is hoping to join his friends this fall on another trip to Roatan.  His breathing has become more difficult, making diving more risky, but he’s searching for additional adaptations that’ll let him continue diving.

Diving with sharks was “pretty exciting,” Andrews says.

Fun on land

For Andrews, the adventures don’t stop at scuba diving.

Thanks to an invention nicknamed The Tank, he can enjoy an occasional paintball outing with his church friends, who helped Andrews design and build the contraption. The Tank is a PVC-pipe frame surrounding his wheelchair, covered with a tarp. The finishing touch is a paintball gun mounted on the front, so that Andrews can shoot while being protected from direct hits.

“I guess my attitude and approach to most everything is that I don’t let much, in terms of my ALS, stand in my way of doing things,” Andrews says.  “We either build something, invent something or adapt something to allow me to participate in just about any activity that somebody comes up with.”

by Christina Medvescek

Augie Nieto (left), a pioneer in the fitness equipment industry, and Mark Mastrov, chairman of 24 Hour Fitness,  present Jerry Lewis with a check representing contributions from the International Health, Racquet and Sportsclub Association (IHRSA).

The 42nd Jerry Lewis MDA Labor Day Telethon proved to be a tremendous success in raising funds for the battle against ALS and other neuromuscular diseases. MDA’s ALS Division co-chairs Augie and Lynne Nieto, and their son Austin, were interviewed live on the broadcast, and were on hand to witness the final “tote” of $63.8 million in contributions and pledges. Nearly $3 million more was raised than at last year’s Telethon – a powerful boost for MDA’s programs of research, services and information.

by Margaret Wahl

In January, MDA announced a new strategic partnership with the ALS Therapy Development Institute in Cambridge, Mass., to identify molecular targets for drug development and to screen potential therapeutic agents for ALS treatment.

MDA, through its fast-track ALS research initiative, Augie’s Quest, pledged to give the ALS TDI at least $6 million a year for three years, to be combined with another $6 million a year from the Institute.

Augie’s Quest projects have been added to MDA’s traditional ALS research program, which is based at academic institutions throughout the world and spans the spectrum from basic ALS-related biology to clinical trials.

“It’s very important that we use all available resources in the fight against ALS,” says Sharon Hesterlee, MDA’s vice president of translational research. “Academic laboratories are very good at performing small, focused studies that help us learn about the underlying causes of the disease, whereas biotechnology companies or groups like ALS TDI use a large-scale industrial approach that depends less on developing ideas and more on trying to look at every biological change associated with the disease with no preconceived notions about the cause.”

Researchers at the ALS TDI are using a large-scale industrial approach to look for biological changes associated with ALS.

Beating all the bushes

“The analogy that I like is the different strategies you might use to find a lost child,” Hesterlee says. “An academic laboratory would interview the child’s friends and family to develop a theory about where the child might be based on his/her personality and past behavior. A biotechnology company, on the other hand, would gather everyone in the town together and march across the landscape in a line so that all possible locations would be checked. The latter approach doesn’t require any information about the lost child because the plan is to simply look everywhere.

“It’s hard to say which approach works better, but it’s very clear that the fewer resources available to you, the more clever you have to be to solve a problem. Academic laboratories usually don’t have access to industrial-scale machines that spit out data, so they have to make educated guesses about what might be causing ALS and design experiments to test their theories. If resources are available, however, you can just start beating all the bushes without having to be extremely clever at the beginning. We have always supported the academic model, but the industrial (beat the bushes) model is relatively new to ALS research. We feel that we need to apply both ideas.”

Different strategies

Recent areas of emphasis at the TDI have been counting and standardizing the number of mutated SOD1 genes in laboratory mice with a genetic type of ALS, and analyzing ALS-associated biochemical changes in the tissues of mice and humans with and without the disease.

Gene counting

Mice with a mutation in the gene for the SOD1 protein develop an ALS-like disease and have been used as models of human ALS since the mid-1990s. (SOD1 mutations can also cause human ALS.) Scientists rely on the ALS SOD1 mouse for access to disease tissue that simply would not be available from humans, such as spinal biopsies.

The most common form of the ALS mouse model has multiple copies of mutated SOD1 genes. In order for scientists to use this mouse effectively, it’s crucial that the gene copy number is consistent and stable from mouse to mouse. Lack of standardization of gene copy number may account for many of the reported discrepancies in experiments that use the ALS SOD1 mouse.

More than 400 mice have had their SOD1 genes counted at the TDI. The researchers have found a 2 percent to 5 percent error rate in the SOD1 copy number reported by the commercial mouse supplier. They use only mice with the same copy number in each of their experiments.

Making comparisons

ALS TDI researchers have taken samples of the spinal cord, brain and leg muscles of ALS-affected mice, as well as normal (“wild-type”) mice and other types of mice, and analyzed and compared them with respect to differences in gene activity (“expression”) by measuring levels of messenger RNA, the chemical made from DNA.

TDI biologists are now analyzing and comparing messenger RNA changes in tissues from ALS-affected mice at eight different time points (30, 50, 60, 80, 90, 100, 110 and 120 days of age), which correspond to presymptomatic ALS, early ALS and fully developed ALS.

TDI biologists are analyzing and comparing changes in tissues from ALS-affected mice at eight time points.

“This data set is the foundation that the Institute will utilize to understand the biological mechanisms associated with disease progression in ALS,” says Steve Perrin, TDI’s chief scientific officer. “Additional gene expression profiling and proteomics [protein level] analysis from other mouse models of neurodegeneration, as well as ALS patient samples, will help scientists at the Institute focus on the most relevant biological pathways for therapeutic development.”

Collection of blood samples from ALS patients is under way, and plans are to analyze muscle and nerve samples from patients as well.

All the tissues will be analyzed in the same manner as the mouse tissues to measure changes in messenger RNA production. Eventually, specific proteins altered in human ALS also will be catalogued.

“The specific changes in these tissues will be compared with those seen in the different animal models, allowing researchers to pinpoint the most crucial disease targets,” Perrin says.

by Margaret Wahl

Emotional-control drug development to move forward, Avanir says

Avanir Pharmaceuticals of Aliso Viejo, Calif., has announced that it will continue developing Zenvia (formerly called Neurodex), a medication designed to control involuntary emotional expression (laughing and/or crying) in ALS and other neurologic disorders. The current Zenvia trial is no longer recruiting participants.

In an Aug. 6 press release, the company announced that it had completed the sale of its antipsychotic drug FazaClo (clozapine) and that it expects the income from this sale and other revenue sources “will be sufficient to finance operating expenses through the end of the next fiscal year, including the initiation of the planned confirmatory phase III clinical trial of Zenvia in patients with involuntary expression disorder (IEED), otherwise known as pseudobulbar affect (PBA).”

The experimental drug Zenvia is designed to control involuntary laughing and crying.

Human stem cells secreting GDNF
protected dying motor neurons

Last month, scientists at the University of Wisconsin-Madison and in Lausanne, Switzerland, announced they had protected motor neurons in ALS-affected rats by transplanting human stem cells modified to secrete a therapeutic protein into their spinal cords. Motor neurons are the muscle-controlling nerve cells affected in ALS.

Masatoshi Suzuki and colleagues, who published their results Aug. 1 in the Public Library of Science online journal PLoS One, inserted genes for glial-derived neurotrophic factor (GDNF), a protein known to protect nerve cells, into cells derived from fetal brain tissue under National Institutes of Health guidelines. They then injected the cells into one side of each rat’s spinal cord. Six weeks later, the side that didn’t get the stem cells showed a 70 percent reduction in motor neuron cell number, while the stem-cell-injected side showed almost no loss of motor neurons.

Unfortunately, however, the surviving neurons did not appear to maintain their normal contacts with muscle fibers, and the rats experienced no functional improvement.

“While these results are encouraging, challenges remain,” said Valerie Cwik, MDA’s medical director and vice president of research. “Future research strategies will need to address this issue.”

It Only Hurts for a Second. Flu season is almost upon us. Influenza is a much greater risk for people with weakened respiratory muscles.  Remember that MDA provides free flu shots for all those registered with the Association. For further information please contact the Health Care Services Coordinator in your local office by calling (800) 572-1717.

Editor’s note: The following is excerpted from the MDA publication Everyday Life with ALS: A Practical Guide.  The guide is free to those registered with MDA. An abbreviated version is available free online at www.als-mda.org/publications/everydaylifeals. For more information, call (800) 572-1717.

Chapter 8: Why is exercise important?

Along with helping to combat stress, proper exercise is important for preventing atrophy of muscles from disuse — a key to remaining mobile for as long as possible — and for keeping your cardiovascular system strong. The key to gaining these benefits is finding the most appropriate exercise for you.

Note: Discuss any type of planned exercise with your health care team, particularly your doctor and physical therapist (PT), to ensure that you don’t push weakened muscles to the point of doing further damage, or create a dangerous level of fatigue.

It’s widely accepted among physicians and therapists that specific kinds of exercise help prevent the development of painful contractures (the permanent tightening of muscles) and can decrease the spasticity (muscle tightness or spasms) that’s common in ALS.

For some people, a moderate amount of daily walking in the early stages of ALS may be all that’s advisable. As the disease advances, you’ll benefit from doing range-of-motion and stretching under supervision of a physical therapist.

Exercise precautions

Never push yourself past the point of fatigue, or attempt to strengthen already weakened muscles. It isn’t clear whether muscles already weak from ALS can be strengthened, but PTs know that weak muscles can be further damaged when pushed too hard.

Generally, keep in mind that if you feel worse after an exercise activity, then you’ve done too much.

Stretching & range-of-motion exercises

Any area of weakness in your muscles is prone to tightness or contracture. Stretching increases joint mobility and improves or helps to maintain soft tissue extensibility.

All joints in the body need to be stretched. If there’s an area of weakness, such as your arms, legs or neck, you’ll need additional stretching there to maintain joint integrity and prevent pain.

In ALS, the shoulders are particularly prone to becoming “frozen,” a painful condition called adhesive capsulitis.

You should perform all of the stretching and range-of-motion movements on your own if you can, or with assistance of a physical therapy professional where needed. Your PT can train your caregiver in performing these stretches. It’s very important that you continue to move or have your limbs moved every day even if you’re too weak to do it on your own. When a caregiver is assisting you with the activities, continue to participate as fully as you can.

Note: Everyday Life contains more information on how to do range-of-motion and stretching exercises.

Walking

Walking speed, duration and terrain may be easily varied to suit your ability and strength. Even small amounts — as little as 5 minutes — of walking can be beneficial to your quality of life.

When you walk, go at a steady, comfortable, safe pace with your arms swinging, if possible. This will maximize the cardiovascular benefit.

You can also perform walking activities on a treadmill or an elliptical training machine. Again, your doctor or physical therapist can help you determine an appropriate duration for walking, and how to monitor the intensity of this type of exercise.

Water-based exercise

Water-based activity as a low-impact form of exercise can be very helpful. The buoyancy of water and resistance to movement decreases the risk of injury while allowing the benefits of exercise.

Simple water exercise — even as basic as walking around in the pool — or swimming laps can provide aerobic conditioning.

Spending time in the water can be extremely relaxing, but that in itself can increase the muscle weakness of ALS. If you reach the “wet noodle” stage, you may have difficulty getting out of the pool. For safety’s sake, a pool with supervision and a lift are recommended.

In later stages of ALS, doing aquatic exercises with the help of a PT can continue to provide cardiovascular benefits.

Bicycling

Both stationary and regular bicycling can be good for people with ALS, although stationary biking has certain advantages. You can do indoor biking in a climate-controlled environment where you can monitor your fatigue and take rest breaks with greater ease.

Contact your physician or PT for intensity and duration recommendations.

Exercise cycles, which are pedaling machines that you can use on any flat surface, are [an] option. Some of these cycles feature a passive/active component: An electronic motor assists in moving the user’s legs or arms and shoulders through the exercise motion, even when the user is entirely passive.

Restorators are another rehab tool that can simulate the motions of pedaling. This pedaling mechanism is mounted on an adjustable stand so it can be placed in front of a chair, and used for arm or leg exercises.

Arm ergometry (cycling with the arms) is a low-impact aerobic alternative to traditional bicycling. This type of cardiovascular exercise really challenges the heart, so be sure to do it with supervision and a doctor’s clearance.

Alternative exercises

Yoga, Pilates and tai chi are all low-impact activities that involve movement of the entire body and often include a mental component that can be meditative or stress relieving.

But remember that low-impact doesn’t mean low-intensity. Use caution to avoid fatigue and injury, and if you’re in a class, make the instructor aware of your medical condition before starting.

As with any exercise program, modification may be necessary over time. Please continue to update your health care team on what exercise regimen you’re involved in so they can make adjustments as needed to assist in maintaining your mobility and safety.