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EP-4734773-A1 - NUTRITIONAL COMPOSITION FOR NEURODEGENERATION AND NEUROTRAUMA

EP4734773A1EP 4734773 A1EP4734773 A1EP 4734773A1EP-4734773-A1

Abstract

The invention relates to a nutritional composition comprising a combination of (i) omega-3 fatty acid DHA with (ii) vitamin B2 and (iii) vitamin D3 and one or more from (iv) choline or a salt thereof and/or choline esters; and (v) dietary fibres and/or dietary butyrate for use in the treatment of neurodegenerative diseases and/or neurotrauma, brain injury and/or brain damage. The invention also relates to a composition comprising a combination of DHA, vitamin B2, vitamin D3 with one or more from (iv) choline or a salt thereof and/or choline esters; and (v) dietary fibres and/or dietary butyrate.

Inventors

  • BROERSEN, LADISLAUS MARIA
  • ROOVERS, Lisanne Marijn

Assignees

  • N.V. Nutricia

Dates

Publication Date
20260506
Application Date
20240627

Claims (16)

  1. 1 . A nutritional composition comprising a therapeutically effective combination of i) omega-3 fatty acids, wherein the omega-3 fatty acids comprises at least DHA; ii) vitamin B2; and iii) vitamin D3, and one or more selected from iv) choline or a salt thereof and/or phosphatidylcholine; and v) dietary fibres and/or dietary butyrate, for use in the treatment of neurodegenerative diseases and/or neurotrauma and/or cerebral palsy, preferably for use in the treatment of neurodegenerative diseases and/or neurotrauma, brain injury and/or brain damage and/or cerebral palsy, wherein vitamin D3 is supplemented in an amount of 5 to 80 pg per day.
  2. 2. The nutritional composition for use according to claim 1 , wherein at least 40 mol % choline is provided in the form of phosphatidylcholine, preferably the molar ratio of choline or a salt thereof to PC is in the range from 40:60 to 60:40.
  3. 3. The nutritional composition for use according to any one of claims 1 - 2, further comprising one or more components selected from vitamin A, C and E, phospholipids, selenium, magnesium and further B vitamins.
  4. 4. The nutritional composition for use according to any one of the preceding claims, wherein the neurodegenerative disease is selected from Alzheimer’s diseases, Parkinson’s disease, Huntington’s disease, frontotemporal dementia and Lewy body dementia.
  5. 5. The nutritional composition for use according to any one of the preceding claims, wherein the treatment of a neurodegenerative disease involves, i.e. comprises treating and/or preventing and/or delaying the symptoms associated with said neurodegenerative disease in a subject that is suffering from said neurodegenerative disease or wherein the prodromal phase of said neurodegenerative disease has been diagnosed in said subject, preferably wherein the symptoms involve, i.e comprises, one or more of: cognitive decline associated with memory loss, reduced attention span, reduced executive function, impairment in performing activities of daily living; and/or motor symptoms associated with tremors, rigidity, bradykinesia, coordination and balance; and/or behavioural and psychological changes associated with depression, anxiety, irritability, fatigue, apathy, social withdrawal and mood swings; and/or sensory disturbances associated with loss of sensation, numbness, tingling, or altered perception of touch, pain or temperature; and/or sleep disturbances associated with insomnia, excessive daytime sleepiness, fragmented sleep, restless legs syndrome and rapid eye movement (REM) sleep behaviour disorder; and/or autonomic dysfunction associated with orthostatic hypotension, urinary problems, incontinence, constipation, changes in sweating and body temperature regulation,
  6. 6. The nutritional composition for use according to claim 1 , wherein the neurotrauma is selected from traumatic brain injury (TBI), spinal cord injury (SCI), and peripheral nerve injuries.
  7. 7. The nutritional composition for use according to claim 6, wherein the neurotrauma is caused by external factors selected from one or more of: occupational hazards including car, sports, and workplace accidents; explosions and blast injuries; electric shock; blunt force trauma; penetrating injuries involving the penetration of an external object, including a bullet or a sharp object, into the brain, spinal cord or peripheral nerves.
  8. 8. The nutritional composition for use according to any one of claims 1 to 7, wherein the treatment of neurodegenerative diseases involves, i.e. comprises an increase in neurite outgrowth in subjects suffering from a neurodegenerative disease and treated with the composition as compared to subjects suffering from said neurodegenerative disease and not treated with the composition and/or wherein the treatment of neurotrauma involves, i.e. comprises an increase in length of neuronal outgrowth in subjects suffering from neurotrauma and treated with the composition as compared to subjects suffering from said neurotrauma and not treated with the composition, preferably wherein the treatment of neurotrauma, brain injury and/or brain damage comprises an increase in length of neuronal outgrowth in subjects suffering from neurotrauma, brain injury and/or brain damage and treated with the composition as compared to subjects suffering from said neurotrauma, brain injury and/or brain damage and not treated with the composition.
  9. 9. The nutritional composition for use according to any one of the preceding claims, wherein the composition is used daily for at least 4 weeks after diagnosis of said neurodegenerative disease and/or after diagnosis or occurrence of said neurotrauma, preferably after diagnosis of said neurodegenerative disease and/or diagnosis or occurrence of said neurotrauma, brain injury and/or brain damage.
  10. 10. The nutritional composition for use according to any one of the preceding claims, wherein the composition comprises daily dosages of: i) 150 to 1200 mg, preferably 200 to 1100 mg, more preferably 250 to 1000 mg DHA per day; ii) 0.8 to 7.6 mg, preferably 1 to 7.4 mg, more preferably in the range of 1.2 to 7.2 mg vitamin B2; iii) 6 to 75 pg, preferably 8 to 70 pg, more preferably 10 to 65 pg vitamin D3; and one or more of: iv) 200 to 1400 mg, preferably 300 to 1200 mg, more preferably 350 to 1100 mg choline based on molar weight of choline, wherein choline is selected from free choline, choline salts and/or choline esters, preferably at least phosphatidylcholine; and/or v) 2.5 to 12.5 g, preferably 3 to 12 g, more preferably 3.5 to 11 .5 g dietary fibres and/or 0.125 g to 0.65 g, preferably 0.025 g to 0.65 g, more preferably 0.043 g to 0.65 g dietary butyrate .
  11. 11 . The nutritional composition for use according to any one of the preceding claims wherein the nutritional composition is a liquid nutritional composition, preferably wherein the nutritional composition is an oral nutritional supplement or a tube feed.
  12. 12. A nutritional composition comprising a combination, based on 100 g dry weight, of: i) 480 - 680 mg DHA; ii) 1 .23 - 1 .53 mg vitamin B2; iii) 38 - 54 pg vitamin D3; iv) 200 - 370 mg choline; v) 9.0 - 11 .3 g dietary fibres, wherein choline is provided in the form of a choline salt and phosphatidylcholine.
  13. 13. The nutritional composition according to claim 12, wherein the nutritional composition further comprises 100 - 170 mg EPA based on 100 g dry weight of the composition.
  14. 14. The nutritional composition according to claim 12 or 13, wherein 1 - 5 wt% choline in the nutritional composition is provided in the form of phosphatidylcholine.
  15. 15. A liquid nutritional composition comprising the combination of iv) DHA; v) vitamin B2; vi) vitamin D3; and one or more from vii) choline or a salt thereof and/or phosphatidylcholine; and viii) dietary fibres and/or dietary butyrate.
  16. 16. Liquid nutritional composition according to claim 15, wherein the composition comprises per 100 kcal i) 20 to 100 mg, preferably 25 to 90 mg, more preferably 30 to 80 mg DHA; ii) 0.4 to 0.6 mg vitamin B2; iii) 1 .3 to 4.5 pg vitamin D3; and further comprises iv) 100 to 1000 mg, preferably 200 to 800 mg, more preferably 300 to 500 mg choline or a salt thereof and/or phosphatidylcholine; and/or v) 0.75 to 2.5 g, preferably 1 .0 to 2.0 g, more preferably 1.1 to 1 .5 g dietary fibres and/or 0.015 to 0.25 g, preferably 0.03 to 0.25 g, more preferably 0.05 to 0.25 g dietary butyrate.

Description

Nutritional composition for neurodegeneration and neurotrauma Field of the invention The present invention is in the field of compositions and nutritional compositions for use in treating neurodegenerative diseases, preferably treating and/or improving the symptoms of neurodegenerative diseases and their use in neurotrauma/brain trauma and/or neurological damage caused by trauma and/or improving functional recovery after brain damage. Background Neurite outgrowth refers to the process by which nerve cells, also known as neurons, extend their projections called neurites. Neurites include both axons and dendrites. Axons transmit electrical or neurochemical signals to other neurons, while dendrites receive signals from neighbouring neurons. When neurons undergo neurite outgrowth, it allows them to establish connections and communicate with other neurons in the brain. These connections are essential for the functioning of the brain and form what is known as the functional connectivity. Functional connectivity refers to the patterns of communication and interaction between different brain regions which involves the synchronized activity of multiple neurons and neural circuits. Neurite outgrowth plays a crucial role in shaping these connections and influencing how brain regions communicate with each other. Neurons extend their neurites towards specific target areas and seek out other neurons or regions of the brain to form connections, allowing the establishment of neural circuits and enabling information processing and transmission. The growth of neurites helps in the formation of synapses, which are the points of connection between neurons, thereby contributing to the overall functional connectivity of the brain. The complex network of neurons is responsible for various brain functions, including sensory perception, motor control, sleep, memory, and cognitive processes by means of sending and receiving signals. Neurodegenerative diseases can disrupt the functional connectivity of the brain, primarily through the accumulation of abnormal proteins, inflammation, and loss of supportive glial cells. Impaired neurite outgrowth in neurodegenerative diseases affects the ability of neurons to form new connections and maintain functional connectivity in the brain. Together this leads to the progressive decline in brain function and the characteristic symptoms associated with these diseases, such as memory loss, movement difficulties, sleep disturbances, and cognitive impairment. Treatment of neurodegenerative diseases focuses on medication, delaying the disease progress, physical therapy, lifestyle modifications and supportive care. Regarding lifestyle modifications, a balanced diet has been shown to play a role in disease management and to slow down disease progression. CN107889992 describes a functional health beverage for preventing or treating dementia containing omega-3 fatty acids, choline, and uridine as active ingredients to reduce disease progression and further comprising vitamins and trace elements. WO2021/034942 describes a dietary supplement ameliorating dietary inadequacies related to brain health or neurodegenerative disease containing two polyphenolic compounds, an omega-3 fatty acid, a water-soluble and oil-soluble vitamin component and magnesium. CN112890136 describes an antioxidant total nutrition powder as adjuvant therapy for the treatment of Alzheimer’s disease comprising DHA, B vitamins, vitamin D, phospholipids, and taurine among many other ingredients. WO2018/226089 focuses on treating impaired motor skills in mammals suffering from Parkinson’s disease (PD) and mentions presence of omega-3 fatty acids, choline and D3 and refers to dietary fibres for its neuroprotective effect in PD patients. Neurotrauma refers to an injury or damage to the brain, spinal cord, or peripheral nerves, typically resulting from a sudden traumatic event. It encompasses a broad range of injuries, including traumatic brain injury (TBI), spinal cord injury (SCI), and peripheral nerve injuries. Traumatic brain injury (TBI) occurs when there is a sudden blow, jolt, or penetrating injury to the head, leading to disruption of normal brain function. TBIs can range from mild concussions to severe injuries causing long-term or permanent neurological deficits. SCI refers to damage to the spinal cord, resulting in loss of motor and sensory function below the level of injury. SCI can lead to varying degrees of paralysis, depending on the location and severity of the injury. Peripheral nerve injuries involve damage to the nerves located outside the brain and spinal cord. These injuries can occur due to trauma, such as lacerations, fractures, or compression, and can result in loss of sensation or motor function in the affected area. Neurotrauma can have significant consequences and may result in physical, cognitive, and psychological impairments. In this regard, neurotrauma can have both direct and indirect effects on neurite outgr