Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
1999-06-16
2001-09-18
Jones, W. Gary (Department: 1655)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C536S023100, C514S002600, C424S009200
Reexamination Certificate
active
06291175
ABSTRACT:
BACKGROUND OF THE INVENTION
In general, the invention relates to methods for treating a neurological disease. Neurological diseases, for example, Alzheimer's disease, provide a unique series of complications for clinicians, patients, and care givers; the diseases often progress rapidly and disrupt a vast number of major life functions. The progressive nature of these diseases makes the passage of time a crucial issue in the treatment process. Treatment choices for neurological diseases, particularly those affecting cognitive function, can be complicated by the fact that it often takes a significant period of treatment to determine if a given therapy is effective. Accordingly, treatment with the most effective drug or drugs is often delayed while the disease continues to progress. A method that would allow one to predict which patients will respond to a specific therapy would provide physical and psychological benefits. As healthcare becomes increasingly inaccessible, the ability to allocate healthcare resources effectively also becomes more important.
SUMMARY OF THE INVENTION
The present invention provides a method for treating a patient at risk for a neurological disease, or diagnosed with a neurological disease. The methods include identifying such a patient and determining the patient's BCHE allele status. The invention provides a method for using the patient's BCHE allele status to determine a treatment protocol which includes a prediction of the efficacy of a therapy for the treatment of a neurological disease. In a related aspect, the invention features a treatment protocol that provides a prediction of patient outcome.
In another related aspect, the invention provides a method for identifying a patient for participation in a clinical trial of a therapy for the treatment of a neurological disease. The method involves characterizing a patient with a disease risk and determining the patient's BCHE allele status. In yet another related aspect, the method further involves determining the patient's BCHE allele status and selecting those patients having at least one wild type BCHE allele, preferably having two wild type BCHE alleles, as candidates likely to respond to a therapy for the treatment of a neurological disease. In a preferred embodiment, the treatment protocol involves a comparison of the BCHE allele status of a patient with a control population and a responder population. This comparison allows for a statistical calculation of a patient's likelihood of responding to a therapy.
In preferred embodiments of two of the above aspects, the prediction of drug efficacy involves cholinomimetic therapies, preferably tacrine, or non-cholinomimetic therapies, preferably a vasopressinergic drug that will be effective in patients with the genotype of at least one non-BCHE-K allele, and preferably two non-BCHE-K alleles. In a preferred embodiment, the invention provides a treatment protocol that utilizes one of the following therapies for a neurological disease: probucol, a monoamine oxidase inhibitor, muscarinic agonist, neurotrophic factor, noradrenergic factor, antioxidant, anti-inflammatory, corticotrophin-releasing hormone (CRH), somatostatin, substance P, neuropeptide Y, or thyrotrophin-releasing hormone (TRH).
In a particular application of the invention, all of the above aspects feature a determination of the BCHE allele status of the patient, where a determination of the patient's BCHE-K allele status as being heterozygous or homozygous, is predictive of the patient having a poor response to a therapy for a neurological disease. In a preferred embodiment, the above methods are used for treating a neurological disease such as Alzheimer's disease, neurofibromatosis, Huntington's disease, depression, amyotrophic lateral sclerosis, multiple sclerosis, stroke, Parkinson's disease, or multi-infarct dementia. In another preferred embodiment, the invention is suitable for treating a patient with a non-AD neurological disease.
In another aspect, the invention provides a method for treating a patient at risk for a non-AD neurological disease by a) identifying a patient with a risk, b) determining the BCHE allele status of the patient, and c) converting the data obtained in step b) into a treatment protocol that includes a comparison of the BCHE allele status with the allele frequency of a control population. This comparison allows for a statistical calculation of the patient's risk for having a non-AD neurological disease. In preferred embodiments, the method provides a treatment protocol that predicts a patient being heterozygous or homozygous for the BCHE-K allele to respond poorly to a cholinomimetic (e.g., tacrine) or specific non-cholinomimetic (e.g., vasopressinergics) therapy for a neurological disease, and a patient who is wild type BCHE homozygous, to respond favorably to the therapy.
In a related aspect, the invention provides treating a patient at risk for or diagnosed with a neurological disease using the above method, and conducting an additional step c) which involves determining the apoE allele load status of the patient. This method further involves converting the data obtained in steps b) and c) into a treatment protocol that includes a comparison of the allele status of these steps with the allele frequency of a control population. This affords a statistical calculation of the patient's risk for having a neurological disease. In a preferred embodiment, the method is useful for treating a neurological disease such as Alzheimer's disease, neurofibromatosis, Huntington's disease, depression, amyotrophic lateral sclerosis, multiple sclerosis, stroke, Parkinson's disease, or multi-infarct dementia. In addition, in related embodiments, the methods provide a treatment protocol that predicts a patient to be at high risk for a neurological disease and responding poorly to a cholinomimetic or particular non-cholinomimetic therapy (e.g., vasopressinergics) if the patient is determined to have both an apoE4 allele and a BCHE-K allele. Such patients are preferably given an alternative therapy.
The invention also provides a method for improving the efficacy of a therapy for the treatment of neurological diseases. The method includes the step of comparing the relative efficacy of the therapy in patients having different BCHE alleles. Preferably, administration of the drug is preferentially provided to those patients with a BCHE allele type associated with increased efficacy. In a preferred embodiment, the alleles of BCHE used are wild type BCHE and BCHE associated with reduced biological activity. Most preferably the allele associated with reduced biological activity is BCHE-K.
As used herein, by “therapy for the treatment of a neurological disease” is meant any therapy suitable for treating a neurological disease. A suitable therapy can be a pharmacological agent or drug that may enhance cognitive function, motor function, or neuronal activity of the central nervous system, peripheral nervous system, or inhibit the further deterioration of any of these faculties.
By “cholinomimetic therapy” is meant any drug that mimics the function of acetylcholine or enhances the activity of acetylcholine synthesizing cells. These drugs include, but are not limited to, inhibitors of acetylcholine degradation (acetylcholine esterase inhibitors such as tacrine), drugs that mimic acetylcholine structure and function, drugs that block acetylcholine uptake by neurons, and drugs that interact with pre-synaptic receptors to induce acetylcholine release from cholinergic neurons.
By “non-cholinomimetic vasopressinergic therapy” is meant a therapy that utilizes a vasopressinergic modulator such as, for example, S12024 (provided by Servier, Les Laboratoires Servier, 22 rue Gamier, 92200 Neuilly sur Seine, France).
By “non-AD neurological disease” is meant a disease other than Alzheimer's disease, which involves the neuronal cells of the nervous system. Specifically included are: prion diseases (e.g., Creutzfeldt-Jakob dise
Amouye Philippe
Schappert Keith
Sevigny Pierre
Wiebusch Heiko
Bieker-Brady Kristina
Clark & Elbing LLP
Goldberg Jeanine
Jones W. Gary
Variagenics Inc.
LandOfFree
Methods for treating a neurological disease by determining... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Methods for treating a neurological disease by determining..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods for treating a neurological disease by determining... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2515647