A 1964 report described the use of Clioquinol in both the treatment and prevention of shigella infection and Entamoeba histolytica infection in institutionalized individuals at Sonoma State Hospital in California. The report indicates 4000 individuals were treated over a 4-year period with few side effects.
Several recently reported journal articles describing its use as an antiprotozoal include:
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Clioquinol's use as an antiprotozoal drug has been restricted or discontinued in some countries due to an event in Japan where over 10,000 people developed SMON (subacute myelo-optic neuropathy) between 1957 and 1970. The drug was used widely in many countries before and after the SMON event without similar reports. As yet, no explanation exists as to why it produced this reaction, and some researchers have questioned whether clioquinol was the causative agent in the disease, noting that the drug had been used for 20 years prior to the epidemic without incident, and that the SMON cases began to reduce in number prior to the discontinuation of the drug. Theories suggested have included improper dosing, the permitted use of the drug for extended periods of time, and dosing which did not consider the smaller average stature of Japanese; however a dose dependant relationship between SMON development and clioquinol use was never found, suggesting the interaction of another compound. Researchers have also suggested the SMON epidemic could have been due to a viral infection with an Inoue-Melnick virus.
Clioquinol is a constituent of the prescription medicine Vioform, which is a topical antifungal treatment. It is also used in the form of a cream (and in combination with betamethasone) in the treatment of inflammatory skin disorders.
Evidence from phase 2 clinical trials suggested that clioquinol could halt cognitive decline in Alzheimer's disease, possibly owing to its ability to act as a chelator for copper and zinc ions. This led to development of analogs including PBT2 as potential therapeutic compounds for the treatment of Alzheimer's disease.
Recent animal studies have shown that clioquinol can reverse the progression of Alzheimer's, Parkinson's and Huntington's diseases. According to Dr. Siegfried Hekimi and colleagues at McGill's Department of Biology, clioquinol acts directly on a protein called Clk-1, often informally called “clock-1,” and might slow down the aging process. They theorize that this may explain the apparent ability of the drug to be effective in the above conditions, but warn against individuals experimenting with this drug.
Research at the Academica Sinica in Taiwan shows that Clioquinol may be effective in increasing the transmission of zinc to the brain, thereby correcting the zinc deficiency found in many children with autism. When this was done to mice displaying autistic behaviour, their autistic traits subsided and their behaviour became almost identical to that of mice who were not autistic. The Academica Sinica researchers hope that psychiatrists will consider prescribing the drug, which is already permitted in Taiwan, to suitable patients.
Continued use and manufacture around the world
In August 2004, Prana Biotechnology, an Australian company and P.N Gerolymatos S.A (PNG) agreed to recognize each other's rights to market clioquinol in their respective territories, with PNG holding right for European territories, and Prana holding rights for US and Japan. Prana has performed research into the use of hydroxyquinolines drugs in the treatment of Alzheimers disease.
In 2001, the Canadian company Paladin Labs bought the rights to market Vioform from Novartis. Vioform is licensed for use in Canada as a topical anti-fungal.
^GHOLZ LM, ARONS WL (1964). "Prophylaxis And Therapy Of Amebiasis And Shigellosis With Iodochlorhydroxyquin". Am. J. Trop. Med. Hyg.13: 396–401. PMID14162901.
^Kager PA (2005). "[Outbreak of amoebiasis in a Dutch family; tropics unexpectedly nearby]". Nederlands tijdschrift voor geneeskunde (in Dutch and Flemish) 149 (1): 51–2; author reply 52–3. PMID15651505.CS1 maint: Unrecognized language (link)
^ abcBosman DK, Benninga MA, van de Berg P, Kooijman GC, van Gool T (2004). "[Dientamoeba fragilis: possibly an important cause of persistent abdominal pain in children]". Nederlands tijdschrift voor geneeskunde (in Dutch and Flemish) 148 (12): 575–9. PMID15074181.CS1 maint: Unrecognized language (link)
^Masters DK, Hopkins AD (1979). "Therapeutic trial of four amoebicide regimes in rural Zaire". The Journal of tropical medicine and hygiene82 (5): 99–101. PMID226725.
^Wadia NH (1984). "SMON as seen from Bombay". Acta Neurol. Scand., Suppl.100: 159–64. PMID6091394.