There are several benefits to the development of multiple drugs that modify autophagy through different mechanisms. Researchers found that the co-administration of verapamil and rapamycin had additive effects in reducing huntingtin aggregation and toxicity. That is, co-administration of the drugs was more effective than administration of either drug alone. One possible therapeutic strategy would be to administer lower doses of two different drugs. A combination therapy may be safer for long-term treatment because the drug-specific complications and side-effects may be reduced due to lower dosages. However, more research is needed before any autophagy-inducing drugs are prescribed for use in treating patients with HD.
- A. Pipathsouk, 4/24/09
Further reading
Raught, et al. "The target of rapamycin (TOR) proteins." Proceedings of the National Academy of Sciences of the United States of America. 2001 Jun 19;98(13):7037-44. Short paper which describes various functions of target of rapamycin (TOR) proteins in fairly technical writing.
Ravikumar, et al. "Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy." Human Molecular Genetics. 2002 May 1;11(9):1107-17.
2001 Jun 19;98(13):7037-44. Fairly technical article which describes experiments aimed to discover whether or not proteins with multiple amino acid repeats could be controlled through the process of autophagy.
Ravikumar, et al. "Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease." Nature Genetics 2004 Jun 36(6):585-95. This technical paper describing the effects of mTOR inhibition was cited in the "mTOR and HD" section.
Sarkar S., et al. "Rapamycin and mTOR-independent autophagy inducers ameliorate toxicity of polyglutamine-expanded huntingtin and related proteinopathies." Cell Death and Differentiation advance online publication, 18 July 2008; doi:10.1038/cdd.2008.110. Very technical paper which describes the effects of autophagy inducers in controlling HD and other diseases caused by malformed proteins.
Thoreen, et al. "Huntingtin aggregates ask to be eaten." Nature Genetics. 2002 Jun;36(6):553-4. Less technical article that describes the role of autophagy in controlling mutant huntingtin aggregates.
Williams et al. "Novel targets for Huntington's Disease in an mTOR-independent autophagy pathway." 2008 May;5(4):295-305 Less technical article which reviewed the role of calpains in HD and different autophagy-inducing therapies was cited in the "Calpains and HD" and the "Combination Therapies" sections.
Last Modified: 10/26/2009
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