Alternatives to Rilutek

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The Limitations of Rilutek

As most people with amyotrophic lateral sclerosis (ALS) know, Rilutek is the only prescription medication that prolongs life. Unfortunately, this increase is only about two months. Some people may enjoy greater benefits, especially those with bulbar-onset ALS, but most people will experience far less than a year of additional life with riluzole (Rilutek). Unfortunately, not every patient is likely to experience any benefit from treatment with riluzole. The drug is not likely to be of benefit to anyone with a tracheostomy, for example. Therefore, it is reasonable and common for people with ALS (PALS) to look for alternatives to Rilutek, or at least medications that can be used in addition to this prescription drug.

Clinical Trials, OR How ALS Treatments Fail

Dozens of potential treatments for ALS have shown promise in laboratory studies. Yet when they have been tested in formal clinical trials, there has been no demonstrable benefit in patient mortality (with the exception of a modest benefit from riluzole). From the researcher’s perspective, a drug that fails in a clinical trial does not merit FDA approval or further development.1 It is then essentially placed in the “failed” pile along with all the other drugs tested.

Symptoms Rather than Survival

There are several other ways to look at these results, however. The trial endpoint of “survival” is a very high bar. Rilutek is the only drug that prolongs survival, but what about improving symptoms? Are people living better in those two months of extra life? One must also consider ways to manage the symptoms of ALS and preserve or improve the quality of life. Patients who receive immunizations against infectious lung pathogens, for instance, protect themselves against various forms of pneumonia that are likely to occur in ALS. Speech and physical therapists can help PALS adapt to the progressive muscular issues that arise during the course of the disease. Specific medications can also help with muscle spasms, pain and sleep disorders. The goal of symptom management is to prolong functional capacity and reduce discomfort; Rilutek is not the drug for this purpose.

Testing More than One Agent

Another way to look at these failed clinical trials is to consider the limitations of their design. Clinical trials are almost always designed to test a single agent or, rarely, the combination of two or three agents at one time. What about testing many agents simultaneously? Given the extensive list of compounds that have been tested in ALS and failed, it is unlikely that a single drug will be able to treat this devastating, progressive disease by itself. Thus, it is reasonable for PALS to consider taking multiple agents simultaneously.

Multiple Targets in ALS

Why might multiple agents work? ALS is a complex disease. It is not due to any single cause, but a collection of potential cell injuries including oxidative damage, excitotoxicity, and intracellular inclusions, to name a few. ALS is the result of several pathological processes which occur simultaneously.2,3 One promising approach might be to intervene in several processes at once. One could target oxidative damage using antioxidants. While there are limits to the dose of any single antioxidant, taking multiple, lower-dose antioxidants may quell oxidative damage with less risk of side effects than any one high-dose agent.

Multiple Targets need Multiple Treatments

Consider Vitamin E. Clinical trials with Vitamin E in ALS have been disappointing4,5; however, one could take modest doses of Propolis, Theanine, alpha-Lipoic acid and taurine along with Vitamin E to potentially extend or enhance the antioxidant effect. Likewise, trials of Coenzyme Q10 have not yielded positive results—a surprise to ALS researchers.1  Coenzyme Q10 was tested in clinical trials because it supports cellular energy production and worked well in laboratory animals with experimental ALS. It even increased the lifespan of those experimental animals.6  What has not been formally tested, however, is the combination of several substances that promote cellular energy. The combination of B vitamins, L-Carnitine, Creatine, and alpha-ketoglutarate along with Coenzyme Q10 could theoretically support cellular energy at various metabolic points within the cell.

Conclusions

Rilutek is a useful agent for which most PALS should be considered an important part of their therapy. However, it is also reasonable to consider additions to Rilutek to possibly help target other areas in which the prescription drug fails to treat. Symptom control is an important feature of ALS treatment and should be optimized at each stage in the disease’s progression. One practical limitation of clinical trials is that they usually compare only one or perhaps two agents at one time. The pathophysiology of ALS is complex—there are various disease processes occurring simultaneously. Therefore, it is reasonable to speculate that multiple, related substances may work better than a single agent. One might consider groups of antioxidants or ingredients to support cellular energy as an adjunct/alternative to Rilutek in ALS. Future clinical trials in ALS should include multiple-ingredient treatments.

References

  1. Kaufmann P, Thompson JL, Levy G, et al. Phase II trial of CoQ10 for ALS finds insufficient evidence to justify phase III. Ann Neurol. Aug 2009;66(2):235-244.
  2. Lawton KA, Cudkowicz ME, Brown MV, et al. Biochemical alterations associated with ALS. Amyotroph Lateral Scler. Jan 2012;13(1):110-118.
  3. Rothstein JD. Current hypotheses for the underlying biology of amyotrophic lateral sclerosis. Ann Neurol. Jan 2009;65 Suppl 1:S3-9.
  4. Desnuelle C, Dib M, Garrel C, Favier A. A double-blind, placebo-controlled randomized clinical trial of alpha-tocopherol (vitamin E) in the treatment of amyotrophic lateral sclerosis. ALS riluzole-tocopherol Study Group. Amyotroph Lateral Scler Other Motor Neuron Disord. Mar 2001;2(1):9-18.
  5. Graf M, Ecker D, Horowski R, et al. High dose vitamin E therapy in amyotrophic lateral sclerosis as add-on therapy to riluzole: results of a placebo-controlled double-blind study. J Neural Transm. May 2005;112(5):649-660.
  6. Matthews RT, Yang L, Browne S, Baik M, Beal MF. Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc Natl Acad Sci U S A. Jul 21 1998;95(15):8892-8897.