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October 01, 1996; 47 (4 Suppl 2) Clinical Trials and Future Research

Drug combination treatment in patients with ALS

Current status and future directions

Hiroshi Mitsumoto, Richard K. Olney
First published October 1, 1996, DOI: https://doi.org/10.1212/WNL.47.4_Suppl_2.103S
Hiroshi Mitsumoto
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Richard K. Olney
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Drug combination treatment in patients with ALS
Current status and future directions
Hiroshi Mitsumoto, Richard K. Olney
Neurology Oct 1996, 47 (4 Suppl 2) 103S-107S; DOI: 10.1212/WNL.47.4_Suppl_2.103S

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Although the cause of ALS remains enigmatic, plausible hypotheses have been generated and new facts are continuously presented to explain the disease process in ALS, as have been summarized in this colloquium. The likelihood that several drugs will be effective in treating ALS is a reality. At present, the first drug available by prescription for ALS, riluzole, appears to have only modest effects in prolonging survival. A consensus has developed that a key strategy for increasing benefit is the treatment of ALS patients with a combination of drugs that are effective individually to achieve additive or synergistic benefits. In fact, a combination of several drugs is the standard practice in the treatment of advanced cancers and infectious diseases. In this report, we review the preclinical data supporting combination treatment for ALS and discuss the issues that need to be addressed with drug combination treatment of patients with ALS.

The effects of combined neurotrophic factors in tissue cultures.

Motor neuron survival in chick embryonic tissue culture is only 4.8% in the control medium, whereas the percentage of the survival increases to 14.5% when insulin-like growth factor-I (IGF-I) is added, 51.9% with basic fibroblast growth factor (bFGF), and 60.7% with ciliary neurotrophic factor (CNTF). [1] When these trophic molecules are combined in the culture media, the percentage of motor neuron survival rises to 76.1% with a combination of bFGF and IGF-I, 87% with CNTF and IGF-I, and 98.2% with bFGF and CNTF. A combination of all three trophic factors (bFGF, IGF-I, and CNTF), however, does not increase the survival further. Concerning the survival of in vitro motor neurons, a combination of bFGF and CNTF appears to be most effective. [1] Although these studies demonstrate a partially additive effect of the combination, [1] similar studies have shown that a combination of CNTF and bFGF results in survival-promoting effects that are more than …

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  • Article
    • The effects of combined neurotrophic factors in tissue cultures.
    • The effects of combined neurotrophic factors in wild-type laboratory animals.
    • The effects of combined neurotrophic factors in animal models for motor neuron disease.
    • Clinical studies in patients with ALS.
    • Issues in combination treatment.
    • Concluding remarks and future directions.
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