I. Preface
I am outraged, as you should be if you or someone you love has Amyotrophic Lateral Sclerosis (aka ALS, Lou Gehrig's disease, and motor neuron disease). It has been 134 years from Dr. Charcot's discovery and analysis of the disease to the present. Yet ALS still has no known cause, cure or truly effective treatment. What other fatal disease that affects all races and both sexes has fared so badly?
In the past ten years, the US has experienced a massive increase in health care spending. For example, during the past year research spending on AIDS, heart disease, and cancer totaled about $24 billion, out of $45 billion spent on research by the drug industry and NIH. During the same period, ALS research spending was about $15 million. Research spending is the absolute key to find that cure for this disease. Further, no one has a diagnostic test for determining if someone has this fatal disease. As a result, it takes thirteen months on average to diagnose. It has been estimated that between 20%-60% of a person's motor neurons have already died by the time the disease is diagnosed.
I have had this disease for the past four years and would like to share some thoughts as to what needs to be done to get more effective treatments and possibly a cure in the next 5-10 years.
II. A Macro view of the US Healthcare Delivery System
When President Bill Clinton took office in the early '90s, the US healthcare system was approximately $900 billion, while the US GNP was $7 trillion. President Clinton recognized that the rate of growth of 14% per year in health expenses was unsustainable as America tried to compete in a world marketplace. For example, the largest cost in a Ford Taurus was not the transmission or the engine; it was the healthcare costs paid for the workers that built it. In addition, Clinton realized the explosion in the population called the "baby boomers," born between 1946 and 1954 after the closure of World War II, would create a huge strain on not only Social Security, but also on Medicare. The number of people paying into those systems would not be sufficient to cover the costs of the aging "baby boomer" population, as this group would be in their peak years for medical services.
Clinton initially proposed that Congress take a close look at the Canadian healthcare system. When that was unsuccessful-due to cries of socialized medicine-he then proposed an elaborate federal bureaucracy equally unpopular with the voters. The result was managed care, which sought to withhold dollars of healthcare cost by restricting patient flow to physician specialists and hospitals. As you're aware, this strategy has clearly failed. Most Americans want to choose their own primary care physician and want whatever specialists they might need when they feel that they need them. Since 1995, the rate of healthcare inflation has increased faster than the rate of GNP growth, so now we have approximately a $9 trillion economy with $2 trillion in healthcare costs in 2002.
In the year 2003, managed care companies are projecting the rate of increased healthcare costs at 15-20% after an average increase in 2002 of 11%, while real inflation in the overall economy is about 2-3% during this same time period.
Clearly, this is unsustainable as we compete for business in a world marketplace. In addition, the aforementioned population demographics work against the US as well because people use more and spend more for healthcare as they age. The largest expenditures for healthcare are typically made in the last year of life. President Bush doesn't seem concerned about healthcare expenses, and as a result, little has been done to curtail costs in the last two years.
At the beginning of President Clinton's first term, health care costs were basically divided as follows: about 50 cents out of every dollar was spent on hospital costs, about 20 cents was spent on healthcare provider costs, 20 cents on drug costs, and the balance expended on skilled nursing facilities, rehabilitation facilities, medical equipment, etc. The focus was on maintaining or curtailing healthcare expenses in the hospitals. This resulted in approximately a five cent savings, or 45 cents out of every dollar in 2002 was spent on hospital costs, 20 cents on healthcare provider costs, but drug costs increased to 25 cents. While managed care companies worked on reducing costs by pushing down on hospitals, total costs still escalated.
What was our ranking in the world by the World Health Organization in terms of quality of care and longevity in 2001? The answer may surprise you. Even though the US spent by far more per capita on healthcare than any other country in the world, we only ranked 44th in terms of healthcare quality. France and Italy were number one and two. The reason for this is that the US has approximately 50 million people without health insurance who generally receive substandard healthcare for themselves and their children. They die younger, as do their children. Healthcare does not have a good value proposition for US consumers!
What does this mean to ALS sufferers? Quite simply, in the decade of massive increases in healthcare spending, ALS sufferers have not received our fair share of the research funding from either the government or from industry. Without the research monies, ALS has had one drug (Rilutek) approved in 10 years. Instead of $13-15 million per year, we need $500 million. Also, you have noticed your healthcare costs escalate to the point that it is getting painful as employers, like GE and others, and even the government are looking to push the massive increases from health insurers off onto us!
III. Major Segments in Healthcare and What They Want
The major segments in healthcare and what role they will play going forward (from an ALS point of view) are: the drug manufacturers, physicians (particularly neurologists), the researchers who perform original research and publish their findings, associations such as ALSA and MDA, the federal government who sponsors drug research through NIH, and our Congressional representatives and Senators who influence NIH spending.
The drug companies want more profits; their motivation is greed. Since it is estimated that there are 30,000 ALS sufferers alive at any one time, they consider ALS to be an orphan disease (defined as fewer than 200,000 sufferers). The drug companies focus their research primarily on the major killers of the US population, which are heart disease, cancer, and AIDS. As a result, much progress had been made with all of these diseases. For example, within 20 years, we have effective treatments to keep AIDS sufferers alive longer or even affect a cure. The difference is that there is major profit potential in curing AIDS, heart disease, and cancer. Unfortunately for ALS sufferers, drug companies find it hard to calculate a return on their investment in finding an effective treatment for ALS. This is the main reason that we only have one drug approved for ALS (Rilutek) in the last ten years. The drug companies will not be investing in research for ALS unless they uncover something that occurs in other major neurological diseases that would have a common use for ALS. The CEOs of the drug industry will maintain their enormous salaries and positions by increasing their company earnings and shareholder value. Thus, we cannot count on these drug companies to change their research programs to focus on ALS.
Neurologists, the physicians who treat patients with ALS, are basically waiting for the NIH, researchers, or drug companies to provide them with an answer. Until then, their primary value is helping patients to live with the disease; they're not actively searching for a cure. Neurological researchers, M.D.s and Ph.Ds, have a host of diseases that they are seeking to cure, which include Parkinson's, stroke, Alzheimer's, and Multiple Sclerosis. Researchers have gone to where the money and recognition are, so that we won't see a flood of researchers going to work on ALS because of the limited funds available. More likely, the researchers will go into diseases where there is a lot of funding. Doctors like Rothstein at Johns Hopkins, Brown at Harvard, Siddique at Northwestern, Apeles at Baylor, and a few other leading researchers in ALS will have to find treatments for ALS. The cavalry won't arrive until funding for ALS has increased.
Associations such as the ALS Association, a group of affiliated chapters and a national organization, the Muscular Dystrophy Association and several others that raise money for neuro muscular diseases cannot be expected to raise the $3-5 billion needed to cure ALS. In addition, the national ALS organization, based in Los Angeles, California, is weak and ineffective in representing the interests of the ALS community at the federal level. The Muscular Dystrophy Association divides its funds among 44 neuro muscular diseases, of which ALS is one. Other organizations arise out of personal association with a given patient, but usually become less efficient when the ALS patient dies; in other words, these organizations have not been a consistent source of funding over time.
In some cases, these organizations fund ALS clinics, usually associated with prestigious medical schools. You should be aware, if you decide to use a doctor at one of these clinics, that he/she might not have your best interest in mind when you want to participate in a new drug trial. Why? Each of these clinics negotiate their own contracts with each drug company which probably contains exclusions that can keep you out of the trial. For example, Washington University School of Medicine, the MDA clinic in St. Louis, ran a BDNF trial for Regeneron Corporation. Regeneron did not want anyone in the trial except for people with FVC's between 60 and 90%, which the clinic accepted but did not inform the ALS sufferers-a clear conflict of interest.
Where do we turn for adequate funding to cure this disease? The answer must be the federal government, which has the deep pockets to find a cure in 5 to 10 years.
The federal government spent about $20 billion in 2001 on medical research through NIH. The National Institute of Neurological Disorders and Stroke (NINDS) is approximately $4 billion of that total and funds all of the neurological disease research on diseases such as Alzheimer's, Parkinson's, ALS, etc. The job of NIH has evolved into providing medical research on what has become an economic basis, not on the basis of social justice as it should be. As near as I can tell, NIH gets instructions from Congress on a basis of saving out year Medicare and Medicaid costs so naturally the most expensive and most prevalent diseases today get a majority of the research funding (i.e., cancer, AIDS, and heart diseases get $4 billion each for research each year and we can measure the results in lives saved).
When Congress decides which diseases they want funded, they decide based on how many people will vote for them because they want to ensure that they stay in power. Also, they're interested in saving Medicare and Social Security from being depleted so they aren't faced with the decision to cut benefits to seniors or bankrupt Medicare and Social Security.
The federal government remains our best choice for funding since it's expected to take about three to five billion dollars of funding over the next five years to cure this disease if Parkinson's and Alzheimer's are any indication. The friends and family of ALS suffers must convince Congress and thereby NIH to spend more money on the disease and to fulfill their mission of providing social justice to all of their constituents.
IV. Issues for ALS Sufferers
1. Research Funding
The number one issue for ALS sufferers is to convince Congress and NIH to allocate adequate research funding because that drives the entire process to find more effective treatments for this disease. Since the NIH currently spends only $15 million out of their budget of $20 billion for ALS research, we must do a better job at the federal level. Cystic Fibrosis, which has the same incidence in the US population as ALS, receives $100 million from the federal government for research. So clearly ALS sufferers must do a better job of bringing our case to the National Institute of Health. Also, ALSA and MDA have not been as effective in dealing with Congress as have the Parkinson lobbyists and the Alzheimer lobbyists. As a matter of fact, The Alzheimer's Association had a study done which showed that in 10 years, the number of Alzheimer patients would rise from 2 to 14 million people at an enormous cost to the federal government. This was sufficient to enough to increase their allocation from NIH from $520 million to $561 million in 2002. They have had 4 new drugs in the last 2 years in addition to a vaccine that has proven effective in mice, as opposed to ALS, which has had one new drug approved in the last 10 years. When an Alzheimer's Association doctor was asked by Senator Arlan Spector if an increase in funding from $520 million to $561 million would cure the disease, the doctor stated that he didn't think so because it would take another 2-3 billion dollars to cure Alzheimer's Disease. The question is why does anyone think it would cost any less to cure ALS?
The next major source of research funding is the ALS organizations that are usually tied to a patient such as Project ALS, Hope for ALS, Ride for Life, all of which generate significant funds (together less than $5 million annually). These organizations raise money to save a particular patient. The question is: what happens if that patient dies? Unfortunately, the history of these organizations is that they are less-than-effective and finally fall apart; most dissolve without the presence of the founding ALS sufferer. Thus, they are an inconsistent source of revenue. Basically, ALS organizations come and go because of a lack of succession planning. The organization must focus on the disease and not the patient. The disease should serve as the focal point of the organization.
Finally, we realize even if the ALS community was to raise $50 million per year, we need $500 million per year to put an end to ALS in the next 5-10 years.
2. Patient Advocacy
As a general statement, it is my experience that most ALS patients, like 99.9% of all neurologists, are waiting for someone else to supply a cure. A cure will not be forthcoming unless ALS patients get involved in the various associations and organizations that are attempting to further our cause. The reason for this is quite simple. The paid members of an ALS organization don't have the motivation or the sense of urgency that the ALS patients have. The greatest number of ALS patients I have seen at the National Advocacy Day in Washington DC is around 40. The question is where are the other 29,960 patients? Why are all ALS suffers not working to find a cure, if not for themselves, for their children and other relatives? All ALS sufferers know what a horrific disease it is. Many of our fellow sufferers lose their ability to walk or speak early in the disease. However, they too must take part in this activity, especially when lobbying Congress who needs to hear personal stories and see the impact of the disease.
Sadly, the family and friends of a deceased ALS patient cannot be counted on to carry the banner forward after that patient dies. I have seen numerous instances where the patient has died, and the husband or wife and family show up to ALSA meetings to give away or sell medical treatment equipment, and we never see them again. The loved ones try to put the disease out of their mind and forget about the painful experience of dealing with ALS. This must not be allowed to continue. We must keep their support on an ongoing basis through an organization assigned for this purpose.
Equally amazing, I have been absolutely stunned at the number of celebrity ALS sufferers who have refused to advocate a cure for this disease. What if Michael J. Fox had said that about Parkinson's? Would Parkinson's be so close to finding a cure today? On the other hand, Alzheimer's patients typically are beyond advocating for themselves yet members of the family step forward to take their place. So when former President Reagan was diagnosed with Alzheimer's, Nancy Reagan stepped forward to be a spokesperson for the cure for Alzheimer's. We have not been successful in letting others advocate for us, so we have to take a much larger role in advocating for ourselves and our children.
3. Accurate Numbers for ALS
Nobody knows how many people have ALS or how many people die from it. There are estimates from statistical data, which are not correct. Normally, ALS patients die from oxygen insufficiency, falls, or choking, but what ends up on the death certificate is something totally unrelated to ALS making it hard to tell how many people actually die from the disease. I wonder, for example, whether a soap opera star's death certificate states coronary thrombosis as the official cause of death, or does it read ALS-induced coronary thrombosis? Since the average time to diagnose the disease is thirteen months for sporadic ALS, how many people a) never get a diagnosis and die from the factors listed above, or b) decide that it isn't worth the time or money to travel and see a neurologist given the fact that there is no cure? How many poor Americans give up because they can't afford the enormous cost of this disease? In addition, since the cause of ALS is not known and could be anything from a virus to an immune system problem, it is difficult to know how many people potentially have the disease unlike heart disease, for example, which is easy to diagnose.
A second question that one has to answer is: as the American population ages, what is the impact of ALS? Does it suddenly go up, as in the case of Alzheimer's, or does it remain at a constant rate? If cancer and heart disease are 99% curable in ten years, this will mean an enormous increase in life span for the US. What happens to the rate of ALS in the US population? Nobody knows the answer to that question.
So we can see that when we talk about 30,000 people with ALS, it is really only an approximation, as is the number of people who die every year. Judging from past trends, one of the ways we can capture government attention and to force the government to provide us with more funding is to stay alive longer.
4. A Fight for More Resources for ALS
As the NINDS budget was growing at 15% per year, it didn't make sense to fight to increase ALS' share of the budget at the expense of other diseases. However, in my view, this is going to stop due to the increasing rate of healthcare expenses year after year. There will be a question of how much should be allocated to Alzheimer's, Parkinson's, and so on. I think that we best prepare ourselves for a time when we have to do battle with these diseases for Congressional support for an increased budget. This will take substantially more and better resources than have been applied to the problem to date.
5. Use of existing pharmaceuticals in ALS, DRUG TRIALS and the mouse model for ALS
As opposed to research efforts to look at the cellular level for the cause of ALS, another approach is to take a look at the existing pharmaceuticals that we have and use those to at least stop the progression of ALS. These trials will still take 2-3 years to prove efficacy. The ALS community is spending millions of dollars on this enticing approach. To date ALS researchers are running tests on drugs that have proven effective in the ALS mouse model (e.g., drugs such as Minocycline and Celebrex).
The FDA must use its power to speed up drug trials for ALS. The trials which normally take years not months are a monument to caution, MEANWHILE 6000 PEOPLE DIE EACH YEAR the trial goes on. ALS needs the same breaks given to AIDS clinical trials by the FDA. ALS patients need to quickly sign up for these trials so researchers have the critical mass needed to begin.
In the mouse model of ALS, everyone in the research community seems to feel that it represents a true model of the ALS disease; while in practice it has proved to be ineffective. We have had numerous drugs that have shown to be effective in the ALS mouse model that have later failed in human trials. A new mouse model must be developed for ALS.
While the knowledge gained from these trials has helped our understanding of ALS, it is much like the proverbial shot in the dark. As a matter of fact, different researchers report different results using the same mouse model and the same drug-one will report great success while the other reports no improvement.
There is always a great variability in dosing and the purity given this research. If sporadic ALS is started by different causes, then we may be discarding effective treatments for a part of the ALS population, because the current model is based on the inherited form of ALS.
V. The Future for ALS Sufferers
While much of this paper has been about the past, the future with an increase in funding can be bright. Stem cell research currently being done in the US and Europe has much potential for, if not curing the disease, at least restoring motor neurons in the spinal cord and brain. Unfortunately, stem cell treatments are more likely to be developed in Europe than in the US because of the sensitivity of the US to the beliefs of the Religious Right. The Religious Right do not believe in using fetal stem cells for treatments in diseases. They insist that this research will lead to the cloning of human beings. In Europe, they seem to have embraced this technology for curing diseases such as ALS; the Italians and British both reported success in the use of stem cells in ALS treatment. The use of fetal stem cells for ALS is likely to be several years off in the US.
Gene therapy is also a potential solution to ALS, especially the familial form and may also be potentially a cure for the sporadic form. Gene therapy will be available in a few years for ALS.
Several prominent researchers believe that there may be multiple causes for ALS. If this is true, then the cure will not be the same for all ALS sufferers. It may require stem cells for one patient, gene therapy for another, or potentially different drugs. At this point, no one knows for sure. Different causes for ALS have been identified by prominent researchers recently, including lipids clogging cells creating cell death of motor neurons, while others are reporting a breakdown of a transporter in the brain called EATT2 as a primary cause.
Potentially, each of these involves the development of a different drug to stop ALS from progressing or cure the disease. Finally, as previously mentioned, research is presently underway to use an existing FDA approved pharmaceutical as a mechanism for stopping the disease from progressing or until a cure is found. Celebrex, Minocycline, Tamoxifen, and an AIDS drug are all being tried in the US on ALS patients with the hope of finding some drug to reduce deaths and/or improve quality of life. The hope is that once a drug is found that stops the progress of ALS, then stem cells can be used to restore bodily function lost by the disease. This research could have been started a few years ago if sufficient research funding had been available.
We must remember that this disease has proven itself very difficult to understand and to stop. A few researchers are beginning to look at the impact of ALS on the entire brain because it is now thought that ALS affects more than three areas of the brain and the spinal cord.
VI. Summary - What needs to be done?
1. ALS sufferers and their caregivers must take an active role in finding funding for this disease.
2. The NINDS/NIH organization must be forced by Congress to allocate more research funding for ALS by more effective lobbying in Congress.
3. We must enlist the ongoing support of the family and friends of ALS sufferers who die.
4. We must continue to educate the American public on the horrific effects of Lou Gehrig's disease.