Last spring, all that was to change, when MDA partnered with fitness industry leader Augie Nieto, who had recently learned he had ALS, and his wife, Lynne, to launch a concentrated fund-raising program called Augie’s Quest.

With funds raised by Augie’s Quest in a series of blockbuster events, MDA teamed up with the Phoenix-based Translational Genomics Research Institute (TGen), whose discoveries have already changed the ALS research landscape.

Using brand new high-speed technology, TGen’s elite scientists and technicians were able to complete a scan of the entire complement of genes of some 1,200 people with and 2,000 people without ALS in just a few months. By fall — in one of the biggest breakthroughs ever in ALS research — TGen had identified some 50 key differences in the DNA of these two groups. You may have seen national news coverage of this announcement late in the year, including stories in the Wall Street Journal and Newsday.

This new information opens a myriad of doors that are likely to provide leads for therapy development. Already, for instance, we know that proteins at the nerve-muscle junction, previously thought to be irrelevant to ALS, may play key roles in at least some cases of this disease.

Proteins that form the “scaffolding” of nerve cells and some that are involved in overzealous responses by the immune system may also be important.

Recognizing that DNA screens are only grist for the mill of drug development, MDA will embark this year on a large-scale effort to identify compounds that act on desired biochemical pathways identified by the screen. The positive “hits” from these biochemical tests will, we hope, become the seedlings of new ALS drugs.

Still another line of MDA-supported research has recently borne fruit as well, thanks to new strategies in the science of blocking, or silencing, toxic genes. Scientists at the University of California-San Diego will soon begin testing an “antisense” compound to block the toxic SOD1 gene in monkeys, with the ultimate goal of launching a clinical trial for people with SOD1-related ALS.

We begin 2007 with a new infusion of optimism and energy. Still more exciting announcements are expected early this year, as ALS research moves into a new era of progress.

Genome-Wide Search Hits Pay Dirt

On Nov. 30, scientists from the Translational Genomics Research Institute (TGen) in Phoenix announced results of their high-tech scan of all the genes (the entire genome) of 1,200 people with and 2,000 people without ALS. The massive project, supported by a $652,000 grant from MDA’s Augie’s Quest, a fast-track ALS research program, in collaboration with TGen, is expected to open up a previously unexplored area of ALS research. Among the differences that the researchers identified between ALS patients and healthy people were some in genes that influence how nerve fibers interact with muscle fibers, a process that until now hasn’t received much attention as a contributor to ALS. Alana Lysholm-Bernacchi and Sarah Brautigam work at TGen’s gene chip fluidics station. “Our findings indicate these genes produce a sort of molecular glue that attaches motor neurons [muscle-controlling nerve cells] to muscle,” said Dietrich Stephan, TGen’s director of neurogenomics and the study’s principal investigator. “It appears that in ALS the nerve is able to peel off the muscle and, when that happens repeatedly, the nerves die.” Nerve fibers interact with muscle fibers at specific points known as neuromuscular junctions. Normally, a tiny space separates these fibers, across which the chemical acetylcholine has to flow for nerve signals to reach muscle tissue. The molecular glue, or “adhesion molecules,” are in the space and keep the nerve and muscle fibers properly aligned. In ALS, the space apparently widens because of a failure of the adhesion compounds to carry out their usual roles. The fast-track research funding approach used by MDA and a new microarray technology provided by Affymetrix, a multinational company with U.S. offices in Santa Clara, Calif., allowed researchers to quickly scan people’s genomes and complete this part of the study in nine months. Next steps center around high-throughput screening for drugs that act on the biochemical pathways identified by the genome screen. TGen’s results suggest the molecular glue that keeps nerve and muscle fibers properly aligned at the neuromuscular junction may be affected in ALS.

Nursing Homes: A Good Move?

by Christina Medvescek

Like hotels and hospitals, there are good and bad nursing homes. Even the best isn’t the same as living at home, but residential facilities offer round-the-clock care that may be impossible to get at home.

Some people with ALS choose to go to nursing homes as an act of control over “being a burden” to others. But often the reason is that caregivers are unable to give care because of age, sickness, employment, location, other responsibilities or simply being overwhelmed.

Moving to a nursing home raises emotions for all concerned — guilt, abandonment, desolation and more.

“My daughter-in-law asked, ‘How could you take him to a nursing home?’” recalls Betty Debban of Cedar Rapids, Iowa, whose husband, Charles, had ALS and lived in a nursing home for five years until his death at age 85. “Well, several years ago we talked and decided that if either of us needed skilled care, we’d go to a facility. People shouldn’t feel guilty, because you have to consider all the ramifications.”

Sometimes life even gets better at a care facility, thanks to activities not available at home, like pool therapy, classes or people to talk to. It’s never easy, but there’s relief in knowing competent care is available when needed.

Figuring It Out

Bonnie Flynn of Gainesville, Fla., says she and her loved one with ALS, Tom Horn, “didn’t understand Medicare” at first, and learned too late that Tom (who died in August 2006) should have ordered medical equipment such as a communication device and wheelchair upgrades while still in assisted living. Once Tom, 67, moved into a skilled nursing facility, “we fought all these battles but he was no longer eligible.”

Nursing homes residents still qualify for hospice, however. Medicare will pay hospice workers to supplement nursing home care for eligible residents, including those on vents. Medicare also pays for brief respite stays at residential facilities, allowing a trial run of a potential location.

All this complexity makes it helpful to have a guide. “Consult an attorney and the Medicaid folks in your state,” advises Leslie LeBlanc, whose elderly mother with ALS lives in a nursing home in Rockland, Maine. He notes that new rules make it harder to give assets to others in order to qualify for Medicaid (which pays for nursing homes, unlike Medicare).

Free, knowledgeable help also can be found at area agencies on aging (available in every state; check the phone book under “senior services”). Counselors or “caregiver specialists” provide information on federal/state programs and nursing home residents’ rights under the law. Counselors also have lists of facilities, questions families should ask, and criteria for comparing facilities.

Choosing the Right Place

Caregiver specialists also can help assess whether a nursing home is the best placement.

Ann Coleman, 78, who lived alone, wishes she had tried moving to a smaller accessible apartment when her ALS progressed, rather than directly to a care facility in Festus, Mo. “I think I could have handled that easily then, with the help of Elder Helpers (in-home aides).”

Instead of a nursing home, a person might be happier in a setting with a livelier mix of people, such as assisted living or an adult care home in a private residence, says Susan Blommer of the Pima Council on Aging in Tucson, Ariz.

A smaller setting allows a better staff-to-resident ratio. By contrast, larger facilities have more to offer. Flynn and Horn enjoyed the restaurantlike dining room and many activities and programs at his state-of-the-art facility, as well as the opportunities to socialize.

Flynn recommends asking if a facility has “ALS protocols” — procedures useful in caring for people who are paralyzed, speechless or on a vent, such as Hoyer lift operation or communicating via alphabet board. If not, ask administrators if they’re willing to learn about ALS, make changes and train staff to meet the unique needs of ALS patients.

Adjusting

Coleman is blunt about the realities of nursing home life.

“They’re concerned about the residents not as a family member would be, but as an institution would be. There’s no comparison to being cared for at home. It was a big change from living alone to living with people in varying stages of Alzheimer’s disease, and being told what to do all the time. I had some adjusting to do both in thinking and in my personal habits.”

The quality of the staff makes all the difference. High turnover and poor communication between shifts results in the frustration of having to constantly retrain staff on special ALS procedures.

“When you have a caring mix of people, care is great and it goes down from there to poor,” says Mike Harrold, 49, who lives in a nursing home in Nanuet, N.Y. Besides missing his 6-year-old daughter, he says the worst part is when “staff treats me like a subhuman.”

Family and friends serve as protectors and advocates. “Your spouse should come at random times” to check on you, Harrold says.

“Learn how things get done,” advises Flynn. After Horn lost his speech, she accompanied him to weekly meet-ings with administrators “to be sure problems got dealt with from the top down.” Before the meeting, Horn would painstakingly dictate his concerns via alphabet board to Flynn — late medications, clueless staff, slow response time — then review them one at a time with administrators.

Ultimately, say individuals and families, attitude adjustment can make an unpleasant situation more bearable.

Notes Betty Debban, “From the beginning, Chuck’s attitude was, ‘This is the way it is, so let’s make the best of it.’ He said nothing is ever going to be perfect, even at home.”

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'Second Life' Leads to Poetry

by Dmitry Rashnitsov

Cathy Wolf used to write funny poetry for her two best friends on their birthdays. She used to work on her college newspaper. She wrote a dissertation to achieve a doctoral degree.

Having received a diagnosis of ALS in 1997, Wolf, 59, has spent her “second life” reconnecting with the writer within. She enjoys composing thought-provoking poetry about living with ALS, politics, ironing or anything else that comes to her mind on those early mornings when she can’t sleep. She especially likes to write about reactions to the news of the day.

“The world is so messed up you have to laugh to keep from crying,” she says.

Switching Muses

Born and raised in Washington, Wolf attended Tufts University in Boston for her undergraduate degree and contin-ued her Ph.D. work in experimental psychology at Brown University in Providence, R.I. Her husband of 38 years, Joel, gently encouraged her to write from their home in Katonah, N.Y.

Mila Sales, Cathy Wolf’s head nurse, puts on Cathy’s Headmaster collar for head support.

“I encouraged her to think about a ‘second’ career involving writing,” Joel said. “It took her a while to get there, but the poetry idea was a natural one for Cathy.”

Wolf spent the better part of her adult life working in the research department at IBM, specializing in human-computer interaction. Even after her tracheostomy, Wolf continued to work for two more years before she went on long-term disability in 2003. Now she uses the technology she helped to create.

Before the diagnosis Wolf ran 15 miles a week, and loved to tinker in her garden, cook meals for friends and family, and perform yoga and modern dance. Not being able to flex her left foot during a dance class in 1996 and pain in her left calf after running alerted her to a problem.

But Wolf’s postive outlook toward life is what keeps her from getting frustrated with the day-to-day hassles of the disease.

“I try to live a normal life in spite of ALS,” Wolf said. “An optimistic spirit, persistence and an independent nature — some say stubborn — have helped me face ALS.”

Wolf’s poems have deep meaning beyond the words in context. They show a person who is still struggling with the diagnosis, and coming to terms with the loss of physical activities that once punctuated her life.

ALS may have robbed Wolf of the ability to speak, but poetry gives her her voice back. She hopes her poetry skills continue to improve but she isn’t that worried about it.

“I am less afraid of failure or the opinions of others,” Wolf said.

by Margaret Wahl

Editor’s Note:
The 17th International Symposium on ALS/MND (Amyotrophic Lateral Sclerosis/Motor Neurone Disease), held in Yokohama, Japan, Nov. 30 through Dec. 2, showcased important research findings, many of which involved MDA research grantees and clinicians. News items from the meeting are marked with this icon:

Report Concludes Military Tie Deserves Further Study

One high-quality study, with adequate allowance made for possible confounding factors, and three studies with some methodological limitations that make them less valuable, all support a relationship between having served in the military and later developing ALS, says a report released Nov. 10. A fifth study, also with limitations, failed to find such an association.

The report is from the Institute of Medicine of the National Academy of Sciences, which describes its role as providing “independent, objective, evidence-based advice to policymakers, health professionals, the private sector, and the public.” It was requested by the Department of Veterans Affairs.

The Institute concludes “there is limited and suggestive evidence of an association between military service and later development of ALS.” It recommends that the Veterans Affairs Department identify all possible ALS risk factors relevant to military service; conduct systematic reviews of the literature on these factors; and conduct further studies to uncover risk factors relevant to military service.

You can read more of the report or purchase the entire text by clicking on “Amyotrophic Lateral Sclerosis in Veterans” at www.iom.edu.

Nonviral Gene Delivery Comes of Age

Delivering genes to the nervous system or muscles using a patented high-pressure injection system may be the “next big thing” in gene therapy, if MDA grantee Jon Wolff’s hunch is correct.

Jon Wolff

Wolff, an MDA grantee at the University of Wisconsin-Madison, has been working with Mirus (www.mirusbio.com), a Madison biotechnology company, to develop gene delivery methods that don’t require the use of viruses.

In October, Mirus announced it has a European patent on its gene-delivery approach, known as Pathway IV, which stands for “intravascular.” The company received a U.S. patent for the technique in 2003.

Wolff says that, although the nonviral technique Mirus has patented can get genes into a large number of cells, “one of the concerns has been its safety, since it requires high intravascular pressure in order to be effective. However, we have conducted an extensive number of safety studies, and the technique appears to be very safe.”

In ALS, candidates for gene therapy include genes for neurotrophic (nerve-nourishing) factors, such as VEGF and IGF1, and compounds that block toxic genes, such as SOD1 genes with ALS-causing mutations.

The experimental drug Zenvia (referred to as Neurodex until recently), developed by Avanir Pharmaceuticals (www.avanir.com) of San Diego for the treatment of unwanted emotional expression, won’t be approved by the U.S. Food and Drug Administration until additional data on safety and effectiveness have been supplied, according to an Oct. 31 press release from Avanir.

The company had hoped to market the drug for the treatment of “involuntary emotional expression disorder” (IEED), a condition associated with certain types of brain injuries and neurologic disorders, including ALS. (The phenomenon, which involves episodes of uncontrollable laughing or crying, is also known as pseudobulbar affect, and is thought to occur because of changes in signaling pathways in the brain.)

Zenvia is a combination of dextromethorphan, which affects signal transmission in the nervous system, and quinidine, which is said to help the body use dextromethorphan more effectively. In 2002, a trial that included 140 people with ALS showed the drug reduced the frequency of IEED episodes and improved quality of life.

The Oct. 31 press release said Avanir anticipates scheduling a meeting with the FDA to discuss the agency’s additional requirements.

In addition, the release noted, Avanir “cannot be certain that once it has met with the FDA, that it will choose to continue with the development of Zenvia as previously planned.”

“Unfortunately, it seems we may still have more work to do,” said James Berg, who was vice president of clinical and regulatory affairs at Avanir until he left the company in November. “It makes me sorry for all of the people that could use this drug and need it.”

The current clinical trial of Zenvia, open since 2003, will remain open until at least March 1, the company says. (See Clinical Trials at www.mda.org; or call Avanir at [858] 622-5200.)

Is Generic Rilutek on the Way?

Impax Laboratories (www.impaxlabs.com) of Hayward, Calif., announced Nov. 22 that it was one step closer to being able to market a generic version of Rilutek (riluzole), the only drug approved by the U.S. Food and Drug Administration for the treatment of ALS. The drug interferes with glutamate, a carrier of signals in the nervous system. Sanofi-Aventis (www.sanofi-aventis.us/live/us/en/index.jsp), headquartered in Paris, now holds a patent on the medication.

In November, the U.S. Court of Appeals for the Federal Circuit reversed an earlier decision by a district court that had prevented Impax from entering the riluzole market. It then redirected the case back to the district court. Impax, its Nov. 22 announcement says, “expects to request that the injunction preventing [it] from launching its generic version of Rilutek be lifted upon return of the case to the lower court.”

Direct Delivery Gets Around Baclofen Sedation

Weakness and paralysis are what first come to mind when thinking about ALS. But for some patients, spasticity and cramps can also be a problem and can cause considerable discomfort or pain. Unfortunately, oral medications for these can have sedative side effects at the necessary doses.

A group from the MDA/ALS Center at Carolinas Medical Center in Charlotte, N.C., reported that the antispasticity drug baclofen can be delivered directly into the spinal fluid of ALS patients via a pump placed in the abdomen, and that this form of delivery avoids the side effects of oral medication. They studied 20 people with ALS who couldn’t tolerate oral medication and who found they were able to reduce or eliminate their oral drugs once they were on the baclofen pump. There were no complications associated with pump insertion.

Stimulating the Diaphragm May Have Merit After All

Stimulation of the diaphragm muscle to improve breathing in people with ALS has had a controversial history. The technique involves implanting in the diaphragm electrodes that send signals through the phrenic nerve, which controls the muscle. Experts’ objections have been based on the known progression of nerve cell loss, including in the phrenic nerve, in this disease.

Now, however, Raymond Onders and colleagues at Case Western Reserve University in Cleveland report that the strategy has been beneficial in eight people with ALS, slowing their decline in respiratory function as measured by forced vital capacity (FVC). There were no deaths and no tracheostomies in the treated patients.

Jeffrey Rosenfeld, who directs the MDA/ALS Center at Carolinas Medical Center in Charlotte, N.C., also tested phrenic nerve stimulation and found it beneficial in two out of the three ALS patients in this small study. Declining FVC stabilized, use of noninvasive ventilation decreased, and the patients assessed their functional ability as greatly improved.

Selecting Early Responders May Speed Drug Testing

It’s now clear that ALS is a heterogeneous disease, and it’s unlikely that any single treatment will work for everyone. But at this time, it’s hard to know which treatments will work for which patients. Some researchers are trying to overcome this problem by altering study designs.

Identifying trial participants whose loss of function curve has changed by one to two units may streamline treatment testing.

Findings from the Forbes Norris MDA/ALS Research Center at California Pacific Medical Center in San Francisco suggest that a subset of participants in a trial who can be classified as “responders” to a treatment might be identified by measuring a decrease in the slope of their loss of function. The report suggests that participants who have a one- to two-unit change in the slope of their ALS Functional Rating Scale scores (indicating a slowing of disease progression) might be selected to form the basis of a smaller clinical trial, one in which nonresponders to the study drug wouldn’t be able to obscure its possible benefits.

EQUIPMENT CORNER
Paying for Assistive Technology: Make alternative financing work for you

by Alyssa Quintero

It’s never too early to start obtaining assistive technology (AT) equipment and services. Realistic financial planning can make time your ally and reduce frustration when it comes to purchasing pricey equipment that can enhance your quality of life.

When Robert Wolf of Ambler, Pa., received a diagnosis of ALS in June 2004, he immediately started to prepare for his AT needs, including home modifications. Wolf knew he couldn’t waste any time.

Wolf, 53, who lives in a one-story ranch house with his wife, Janice, decided to make extensive modifications to his existing home rather than look for a new place to live that was accessible.

“With ALS you have very little control,” Wolf explained. “What you do have control over is readying conditions and trying to anticipate what you’re going to need. We looked at what home modifications were needed to keep moving forward without making it difficult for my wife and caregivers in the future.”

Wolf, who has limb-onset ALS, isn’t using a wheelchair — yet — but he recently borrowed a power wheelchair to see what types of home modifications he needed.

“I maneuvered it around the house to see where the pitfalls were, so we used that as a gauge to help us decide what would work and what had to be changed. It was purely by experiment that we figured out what we needed,” Wolf said.

Wolf consulted with Interiors for Independence (www.interiorsforindependence.com), and he worked with Marlene Weiner, company founder and licensed occupational therapist. She made suggestions and recommendations that helped move Wolf’s plan into the construction stage.

Some of the modifications included: widening doorways; bathroom modifications; an enlarged master bedroom for more access; a wheelchair ramp in the garage for access to an adapted vehicle; and a concrete walkway that’s ramped up to the patio for backyard access.

Thus, even before Wolf’s in a wheelchair full-time, his house will be equipped for universal access.

Now, how do you pay for a project like this?

The Financing Issue

As with purchasing any AT equipment and services, the expenses can mount quickly. Luckily, Wolf learned about the Pennsylvania Assistive Technology Foundation’s (PATF) alternative financing program (AFP) before he began construction.

In “Accessing and Acquiring Assistive Technology” (November-December 2006), we first told you about the AFP, a federal/state loan program available in 33 states that grants low-interest loans to people with disabilities to help fund AT equipment and services.

The loans are commonly used to purchase big-ticket items, including adaptive vehicles, home modifications, computer hardware/software, communication devices and mobility equipment (scooters and power or manual wheelchairs).

Because ALS can take a toll on a family’s finances, Wolf saw this as a great opportunity to get the project moving without paying a huge amount of interest, as one would with a traditional bank loan.

“I wasn’t looking for a handout, but I was looking for something that would be low interest that would help get us over the hump in terms of the modifications,” Wolf explained.

The loan process lasted about three weeks, and Wolf emphasized: “That was actually the easiest and most con-venient part of this whole process. Once I passed the litmus test as far as the loan criteria, it was just a piece of cake.”

With a manageable monthly payment — thanks to a low interest rate — Wolf says the hardest part, at least for his wife, was living with the mess brought by the modifications.

Wolf recommends the alternative financing program to others with ALS who are confronting similar challenges with AT purchases because the program offers “flexibility toward funding anything that assists with your disability needs.”

“The financial arrangement is very good because you’re locked in at a 4 percent interest rate,” Wolf added. “That in itself is a substantial savings right there. It really could be instrumental in helping a lot of people complete a project like this.”

Planning Ahead

In addition to planning ahead for a speech-communication device or a power wheelchair, it’s a good idea to think about home modifications that will be necessary for you to keep living comfortably in your home.

People on fixed incomes or those who don’t qualify for traditional bank loans may find AFPs more receptive to their applications. AFPs also make allowances for poor credit, especially if it’s related to a person’s disability.

The interest rates and alternative financing loan programs may vary from state to state, so be sure to visit the RESNA (Rehabilitative Engineering and Assistive Technology Society of North America) Web site (www.resna.org/AFTAP/state/index.html) to locate your state program’s contact information.

Robert Wolf shows the ramp being added to his garage that will give him ready passage between his house and his accessible van.

To make this process a bit easier, Wolf recommends that you make a financial plan as early as possible following a diagnosis and anticipate your AT needs, which may range from a power wheelchair and a communication device to an adapted vehicle and home modifications.

“What people need to focus on is the flexibility of this type of loan,” he said. “It really is the best of all worlds because you can do low-interest financing for lifts, ramps, home modifications, vehicles, you name it. It’s ideal for people who are worried about their day-to-day finances and just need a longer-term picture to be able to get through it.”

It’s never too early to plan.