Max
08-14-2001, 02:25 PM
Old Drugs May Fight 'Mad Cow' Disease
By Will Boggs, MD
NEW YORK (Reuters Health) - Two old drugs may prove useful in treating the fatal brain malady Creutzfeldt-Jakob disease (news - web sites) (CJD)--including the form related to ``mad cow'' disease, scientists at the University of California, San Francisco (UCSF) have found.
Prion diseases, including CJD, result from the misfolding of prion protein into a shape that somehow copies itself and causes progressive loss of brain function. The form of CJD linked to eating meat infected with mad cow disease is called variant Creutzfeldt-Jakob disease, or vCJD. All forms are invariably fatal.
But new research in mice suggests that two long-used drugs--one for malaria, the other for schizophrenia--may fight prion disease.
Dr. Stanley B. Prusiner and colleagues screened a variety of drugs for their ability to prevent the misfolding of prion protein and to clear from cells whatever misfolded prion protein was already there.
Their search uncovered the schizophrenia drug chlorpromazine and quinacrine, a drug long used to treat malaria, according to a report in the August 14th issue of Proceedings of the National Academy of Sciences (news - web sites).
Chlorpromazine prevented abnormal prion protein formation in cells grown in the laboratory at doses similar to those used to treat schizophrenia, the report indicates. And quinacrine was 10 times as powerful as chlorpromazine in preventing the misfolding of prion protein, the authors note.
Based on these results, the researchers believe quinacrine or chlorpromazine could be used immediately to treat such prion diseases as CJD. Whether the two drugs might be even more effective when used together remains to be seen.
In fact, two CJD patients have already received quinacrine at UCSF. The family of one patient, a 20-year-old UK woman with symptoms of vCJD, says she has undergone an ``extraordinary transformation'' since beginning treatment, according to British media reports.
But the scientists are cautious about the potential success of these two drugs.
``I don't want to raise any unrealistic hopes,'' study co-author Dr. Carsten Korth told BBC Radio. ``We have treated two patients and one of them did not improve and the other, it is too early to tell.''
A spokesman for the Department of Health in London said experts from the National CJD Surveillance Unit are in close contact with Prusiner and his colleagues over this research.
``They have been having discussions about how it can be progressed. We are looking at the possibility of taking it forward--it's a very encouraging piece of research,'' the spokesman told Reuters Health.
But he also pointed to a major obstacle--the fact that there is currently no way of definitively diagnosing vCJD until after death. This makes it difficult to be certain the drug is treating the disease and not another condition with similar symptoms, according to the spokesman.
SOURCE: Proceedings of the National Academy of Sciences 2001;98:9836-
By Will Boggs, MD
NEW YORK (Reuters Health) - Two old drugs may prove useful in treating the fatal brain malady Creutzfeldt-Jakob disease (news - web sites) (CJD)--including the form related to ``mad cow'' disease, scientists at the University of California, San Francisco (UCSF) have found.
Prion diseases, including CJD, result from the misfolding of prion protein into a shape that somehow copies itself and causes progressive loss of brain function. The form of CJD linked to eating meat infected with mad cow disease is called variant Creutzfeldt-Jakob disease, or vCJD. All forms are invariably fatal.
But new research in mice suggests that two long-used drugs--one for malaria, the other for schizophrenia--may fight prion disease.
Dr. Stanley B. Prusiner and colleagues screened a variety of drugs for their ability to prevent the misfolding of prion protein and to clear from cells whatever misfolded prion protein was already there.
Their search uncovered the schizophrenia drug chlorpromazine and quinacrine, a drug long used to treat malaria, according to a report in the August 14th issue of Proceedings of the National Academy of Sciences (news - web sites).
Chlorpromazine prevented abnormal prion protein formation in cells grown in the laboratory at doses similar to those used to treat schizophrenia, the report indicates. And quinacrine was 10 times as powerful as chlorpromazine in preventing the misfolding of prion protein, the authors note.
Based on these results, the researchers believe quinacrine or chlorpromazine could be used immediately to treat such prion diseases as CJD. Whether the two drugs might be even more effective when used together remains to be seen.
In fact, two CJD patients have already received quinacrine at UCSF. The family of one patient, a 20-year-old UK woman with symptoms of vCJD, says she has undergone an ``extraordinary transformation'' since beginning treatment, according to British media reports.
But the scientists are cautious about the potential success of these two drugs.
``I don't want to raise any unrealistic hopes,'' study co-author Dr. Carsten Korth told BBC Radio. ``We have treated two patients and one of them did not improve and the other, it is too early to tell.''
A spokesman for the Department of Health in London said experts from the National CJD Surveillance Unit are in close contact with Prusiner and his colleagues over this research.
``They have been having discussions about how it can be progressed. We are looking at the possibility of taking it forward--it's a very encouraging piece of research,'' the spokesman told Reuters Health.
But he also pointed to a major obstacle--the fact that there is currently no way of definitively diagnosing vCJD until after death. This makes it difficult to be certain the drug is treating the disease and not another condition with similar symptoms, according to the spokesman.
SOURCE: Proceedings of the National Academy of Sciences 2001;98:9836-