Use of medium chain triglycerides for the treatment and prevention of Alzheimer's disease and other diseases resulting from reduced neuronal metabolism

Abstract

Methods and compositions for treating or preventing, the occurrence of senile dementia of the Alzheimer's type, or other conditions arising from reduced neuronal metabolism and leading to lessened cognitive function are described. In a preferred embodiment the administration of triglycerides or fatty acids with chain lengths between 5 and 12, to said patient at a level to produce an improvement in cognitive ability.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. application Ser. No. 09 / 845,741 filed May 1, 2001, entitled “Use of Medium Chain Triglycerides for the Treatment and Prevention of Alzheimer's Disease and Other Diseases Resulting from Reduced Neuronal Metabolism,” which claims priority to U.S. Provisional Application No. 60 / 200,980 filed May 1, 2000, entitled “Use of Medium Chain Triglycerides for the Treatment and Prevention of Alzheimer's Disease and Other Diseases Resulting from Reduced Neuronal Metabolism.”FIELD OF THE INVENTION [0002] This invention relates to the field of therapeutic agents for the treatment of Alzheimer's Disease, and other diseases associated with reduced neuronal metabolism. BACKGROUND OF THE INVENTION [0003] Alzheimer's Disease (AD) is a progressive neurodegenerative disorder, which primarily affects the elderly. There are two forms of AD, early-onset and late-onset. Early-onset AD is rare, strikes susceptible indivi...

AI Technical Summary

Benefits of technology

[0024] The present invention also provides a method of treating or preventing dementia of Alzheimer's type, or other loss of cognitive function caused by reduced neuronal metabolism, comprising administering an effective amount of free fatty acids derived from medium chain triglycerides to a patient in need thereof.

[0025] The present invention also provides a method of treating or preventing dementia of Alzheimer's type, or other loss of cognitive function caused by reduced neuronal metabolism, comprising administering an effective amount of a medium chain triglyceride prodrug to a patient in need thereof.

[0026] The present invention also provides a method of treating or preventing dementia of Alzheimer's type, or other loss of cognitive function caused by reduced neuronal metabolism, comprising administering an effective amount of a therapeutic agent which induces utilization of fatty acids and development of ketosis to a patient in need thereof.

Problems solved by technology

As the disease progresses, additional cognitive functions become impaired, until the patient is completely incapacitated.

Currently, no effective prevention or treatment exists for AD.

These drugs do not address the underlying pathology of AD.

Since the disease continues, the benefits of these treatments are slight.

However, the toxicity of Aβ peptide and fibrils remains controversial.

However, the amyloid cascade hypothesis remains controversial.

Increasing the dosage of the E4 allele increases the risk of AD, and lowers the age of onset.

Decreased access to triglycerides results in decreased availability of fatty acids and decreased production of ketone bodies, and hence a decreased alternative energy source for cerebral neurons.

This reduction in energy supplies may become critical when glucose metabolism in compromised.

Reduced glucose metabolism results in critically low levels of ATP in AD patients.

Additionally, molecular components of insulin signaling and glucose utilization are impaired in AD patients.

Hence, genetic risk factors for AD may result in slightly compromised neuronal metabolism in the brain.

Without ketone bodies to use as an energy source, the neurons of the AD patient brain slowly and inexorably starve to death.

However, since insulin is a polypeptide and must be transported across the blood brain barrier, delivery to the brain is complicated.

Large dose of insulin in the blood stream can lead to hyperinsulinemia, which will cause irregularities in other tissues.

Both of these shortcomings make this type of therapy difficult and rife with complications.

Neurons are very specialized and can only efficiently metabolize a few substrates, such as glucose and ketone bodies.

This limited metabolic ability makes brain neurons especially vulnerable to changes in energy substrates.

Hence, sudden interruption of glucose delivery to the brain results in neuronal damage.

Neurons of the brain cannot efficiently oxidize fatty acids and hence rely on other cells, such as liver cells and astrocytes to oxidize fatty acids and produce ketone bodies.

However, because they are rapidly utilized, the concentration of ketone bodies in the blood is very low.

Since the brain has such high energy demands, the liver oxidizes large amounts of fatty acids until the body becomes literally saturated in ketone bodies.

Therefore, when an insufficient source of ketone bodies is coupled with poor glucose utilization severe damage to neurons results.

Since the defects are limited to the brain and peripheral glucose metabolism is normal, the body does not increase production of ketone bodies, therefore neurons of the brain slowly starve to death.

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