DESCRIPTION
METHODS FOR PROMOTING NEURONAL DEVELOPMENT AND/OR HEALTH ซึ่งประกอบรวมด้วย ADMINISTRATION OF A COMBINATION OF DOCOSAHEXAENOIC
ACID AND ALPHA-LIPOIC ACID
TECHNICAL FIELD
[0001] The การเปิดเผยนี้ relates to method(s) for promoting neuronal health and development, as well as accelerating the development of neuronal activity and/or improving electrochemical synapse signaling, ซึ่งประกอบรวมด้วย providing a nutritional
composition ที่รวมถึง alpha-lipoic acid ("ALA") and โดโคซาเฮกซาอีโนอิก แอซิด ("DHA").
The methods disclosed herein include nutritional compositions suitable for
administration to adult and pediatric subjects.
BACKGROUND ART
[0002] The brain makes up only 2% of total body weight, yet it is a demanding organ that uses up to 30% of the day's calories and nutrients. (Harris, J.J. et al, The Energetics of CNS White Matter. Jour. of. Neuroscience, Jan. 2012: 32(1): 356-371). The human brain and nervous system begin forming very early in prenatal life and both continue to develop until about the age of three. This early development can have
lifelong effects on overall brain and nervous system health. Accordingly, brain nutrients can be important additives in the diets of infants, children and pregnant and lactating women because of their ability to promote early brain development and prevent and protect from brain and nervous system injury or illness. Additionally, brain nutrients are important for adults, as many nutrients promote nervous system repair and provide
neuroprotective health benefits.
[0003] Numerous nutrients are believed to be involved with supporting healthy brain development. Recently, however, it has been discovered herein that ALA, which is also commonly known as lipoic acid ("LA"), may accelerate the development of
neuronal activity thus enhancing neuronal development and cognitive function.
[0004] Given the early development of the nervous system, what is needed is a method for promoting neuronal health and development, in order to support brain and nervous system health. Accordingly, provided herein are methods for accelerating the development of neuronal activity and/or improving electrochemical synapse signaling in a target subject by providing a nutritional composition ซึ่งประกอบรวมด้วย ALA. Moreover,
these nutritional compositions may have additive and/or synergistic nervous system health benefits.
2
DISCLOSURE OF THE INVENTION
[0005] Briefly, the การเปิดเผยนี้ is directed, in an embodiment, to a method for promoting neuronal development by providing a nutritional composition ซึ่งประกอบรวมด้วย ALA and DHA. In some embodiments, the nutritional composition may also ประกอบรวมด้วย lactoferrin, at least one prebiotic, at least one probiotic, and mixtures thereof. It is
believed that DHA may act synergistically with ALA to accelerate neuronal activity
and/or promote and strengthen electrochemical synapse signaling in a subject.
[0006] In certain embodiments the nutritional composition may further ประกอบรวมด้วย at least one additional long chain polyunsaturated fatty acid ("LCPUFA") other than
DHA, sialic acid, a prebiotic source, a probiotic source, fl-glucan, an iron source, and/or mixtures of one or more thereof.
[0007] Due to critical brain development during the first years of life, in some embodiments the nutritional composition provided ประกอบรวมด้วย an infant formula or a pediatric nutritional composition. Additionally, the nutritional compositions described herein may be useful as medicaments or nutritional supplements for promoting
neurological health in subjects with a neural degenerative diseases and/or brain injury. Further, the nutritional compositions of the การเปิดเผยนี้ may provide
neuroprotective health benefits and promote overall brain and nervous system health.
[0008] It is to be understood that both the foregoing general description and the following detailed description present embodiments of the disclosure and are intended to provide an overview or framework for understanding the nature and character of the disclosure as it is claimed. The description serves to explain the principles and
operations of the claimed subject matter. Other and further features and advantages of the การเปิดเผยนี้ will be readily apparent to those skilled in the art upon a reading of the following disclosure.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] The patent or application file contains at least one drawing executed in
color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
[0010] รูป 1 provides an example illustration of a few of the burst parameters described herein.
[0011] รูป 2 illustrates autocorellograms from two different units in a network.
3
[0012] รูป 3 displays a qualitative comparison of effects induced by DHA or
alpha-lipoic acid, as illustrated by in vitro spike trains for 19 neurons over 60 seconds of selected concentrations for both DHA and ALA.
[0013] รูป 4 displays a qualitative comparison of effects induced by DHA, ALA, a combination of DHA and ALA, hBDNF and the vehicle DMSO in a concentration-
dependent manner on the cortical network activity in vitro.
[0014] รูป 5 displays a fitted curve for DHA with calculated slope (Hill
coefficient, nH). At the highest tested concentrations of 100 pM DHA the activity decline reached 63.6 % of native activity.
[0015] รูป 6 displays effective concentration for alpha-lipoic acid causing 10 and 50% activity change (ECio and EC50) and slope (Hill coefficient, nH). At 100 pM alpha-lipoic acid the activity reached 91.5 %, at 1 mM 83.6 % and at 5 mM 43.9 % of
control (0.1 % DMSO) activity.
[0016] รูป 7 displays the comparison of effects of DMSO vs. DHA on the
cortical network activity in vitro. Displayed are 12 activity describing parameters in 4
categories for treatment of 9 accumulating concentrations in the range from 100 pM to
100 pM (mean ± standard error, Student's unpaired t-test: * p ** p *** p
0.001).
[0017] รูป 8 shows the comparison of effects of DMSO versus DHA on the
cortical network activity in vitro. Displayed are 12 activity describing parameters in 4
categories for treatment of 9 accumulating concentrations in ranges from 100 pM to 100
pM (mean ± standard error, Student's unpaired t-test: * p ** p *** p
0.001).
[0018] รูป 9 shows the calculated effective concentration for a combination of DHA and ALA, which causes a 50%, activity change (EC50).
[0019] รูป 10 shows the effective concentration for ALA causing a 10% and 50% activity change (ECio and EC50).
[0020] รูป 11 illustrates the comparison of effects of DMSO vs. ALA on in vitro cortical network activity. Displayed are 12 activity describing parameters in 4 categories for treatment of 9 accumulating concentrations of ALA ranging from 10 nM to 5 mM.
[0021] รูป 12a illustrates feature charts for 100 pM ALA and the combination of
20 pM DHA and 100 pM ALA. Sixty parameters at one selected concentration indicate the similarities and differences for ALA alone and ALA in combination with DHA. From
4
this figure, it can be seen that the mixture of DHA and alpha-lipoic acid induces different activity patterns in the categories of general activity, burst structure, oscillation and
synchronicity.
[0022] รูป 12b illustrates stepwise projection for 10 pM DHA in combination with 100 pM ALA and for 1mM ALA. The burst rate is significantly increased between the step from 10pM ALA to 100 pM ALA.
[0023] รูป 12c illustrates an overview of the activity charts comparing a
combination of DHA and Lipoic acid to Lipoic acid and a vehicle containing DMSO. The parameters are shown within the four general categories: general activity, burst
structure, oscillatory behavior, and synchronicity.
[0024] รูป 13 illustrates an overview of activity charts of the combination of DHA and ALA (A), ALA (B), hBDNF (C) and the pro-cognitive drug donepezil (D). As can be seen from รูป 11, the combination of DHA and ALA, hBDNF and Donepezil increase the neuronal network activity in certain concentration ranges.
[0025] รูป 14 illustrates the effect of hBDNF versus 0.1 % DMSO vehicle on 12
activity-describing parameters in four categories and displays a snapshot of the activity changes induced by hBDNF.
[0026] รูป 15 illustrates the chronic effects of hBDNF versus a vehicle of BDNF and water on neuronal activity parameters spike rate and burst rate. hBDNF at 20 ng/ml increases the general activity at every recorded time point which can be translated into an accelerated neuronal activity development of approximately one week.
BEST MODE FOR CARRYING OUT THE INVENTION