SODIUM L-LACTATE INFUSION FOR EARLY DIAGNOSIS OF PARKINSON'S DISEASE

Abstract

Parkinson's disease is characterized by degeneration of highly metabolic dopaminergic neurons which produce clinical signs to include tremor, rigidity, and glabellar reflex. There are few objective, inexpensive, sensitive, and specific tests for early diagnosis of Parkinson's disease. In this invention, patients who manifest early objective signs of possible Parkinson's disease are pretreated with a supplement to increase central nervous system NAD.sup.+, and then subsequently administered a sodium L-lactate infusion after which the signs of early Parkinson's disease are recorded. Remission of the early signs of Parkinson's disease is diagnostic for Parkinson's disease. A clinical trial is suggested.

Claims

1. A method to diagnose Parkinson's disease in a human subject comprising: administering nicotinamide or an equivalent, derivative or analog thereof to the subject; infusing sodium L-lactate or a salt of L-lactate via an intravenous access to the subject; and recording a decrement in a Parkinson motor response in the subject.

2. The method of claim 1, wherein an equivalent, derivative or analog thereof is nicotinic acid, nicotinamide riboside, or nicotinic acid riboside.

3. The method of claim 1, wherein a Parkinson motor response is tremor, cogwheel rigidity, or glabellar reflex.

4. The method of claim 1, wherein an equivalent, derivative or analog thereof is nicotinic acid, nicotinamide riboside, or nicotinic acid riboside and wherein a Parkinson motor response is tremor, cogwheel rigidity, or glabellar reflex.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0034] The concepts of the instant invention can be summarized as follows: [0035] 1. The etiologies of Parkinson's disease are many; however, the underlying dysfunction of dopaminergic neurons can be explained by the hypermetabolic energy imbalance requirements of these dopaminergic neurons, which are structurally and functionally distinct from other neurons. [0036] 2. L-lactate can restore the energy deficit in dopaminergic neurons, either directly as a fuel to increase ATP, or as a buffer to increase the efficiency of aerobic glycolysis. [0037] 3. Restoring the energy balance in compromised dopaminergic neurons can be clinically assessed by measuring motor functions including, resting tremor, cogwheel rigidity, and glabellar reflex.

[0038] The early diagnosis of Parkinson's disease is not easy, requiring careful examination skills even challenging a very skilled neurologist. One criteria includes bradykinesia and either tremor or rigidity. There are no good laboratory tests, and brain scans including advance dopamine imaging is expensive and not conclusive. A challenge with levodopa therapy is sometimes required to confirm the diagnosis of Parkinson's disease, and such a challenge is not without substantial risks.[32] In the instant invention, three objective physical examination findings are measured to include resting tremor, cogwheel rigidity and/or glabellar reflex, and remission of the motor responses after L-lactate infusion is diagnostic of Parkinson's disease.

[0039] Three common forms of tremors observed in patients with Parkinson's disease include resting tremors, postural tremors, and action tremors. Resting tremors with combined frequencies of 4-5 Hz and 6 Hz diagnose Parkinson's disease in greater than 80% of patients with tremor; however, tremor frequency is not easy to assess in most clinical situations, which confirms the utility of the instant invention. Resting tremor needs to be separated from tremor of other causes.[33]

[0040] Cogwheel rigidity is a hallmark of Parkinson's disease. It can be assessed by flexion of the wrist or elbow and commonly occurs in the frequencies of 6 Hz and 8-9 Hz, which are not easily assessed in the clinic. It needs to be distinguished between rigidity from pseudo-parkinsonism which is one utility of the instant invention.

[0041] Although the glabellar reflex has been used as a diagnostic criteria by neurologists for decades, its use is controversial with poor correlation with (DAT) [.sup.123I] FP-CIT SPECT scanning. It poorly discriminates between patients with essential tremor vs. Parkinsonian tremor.[34]However, clinical studies demonstrate reversal of the glabellar reflex with successful levodopa treatment in patients with Parkinson's disease.[35] This reflex is easily quantified and can be easily conducted at the bedside. Incorporation of this reflex in the instant invention teaches away from present diagnostic testing for Parkinson's disease.

Steps in the Method to Diagnose Early Parkinson's Disease

[0042] 1. Three signs of suspected Parkinson's disease are evaluated on numeric scales and recorded. These signs include resting tremor, cogwheel rigidity, and glabellar reflex. [0043] 2. Patients are subsequently treated to increase CSF NAD.sup.+ with nicotinamide, the preferred embodiment, or other agents known to increase NAD.sup.+ levels to include but not limited to nicotinic acid, nicotinamide riboside, or nicotinic acid riboside.[18] [0044] 3. The three signs of suspected Parkinson's disease are reevaluated and recorded. [0045] 4. An isotonic, intravenous solution comprised of L-lactate infusion is administered with an initial loading dose 300 mol/kg over 5 minutes followed with a continuous infusion of 20 mol*kg.sup.1*min.sup.1 for .sup.120 minutes. [0046] 5. After L-lactate infusion, signs of resting tremor, cogwheel rigidity, and glabellar reflex are evaluated and recorded. [0047] 6. Remission of resting tremor, cogwheel rigidity, and/or glabellar reflex is diagnostic of Parkinson's disease.

REFERENCES

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