EP2063880A2 - Composition destinee au traitement de la sclerose laterale amyotrophique - Google Patents
Composition destinee au traitement de la sclerose laterale amyotrophiqueInfo
- Publication number
- EP2063880A2 EP2063880A2 EP07823842A EP07823842A EP2063880A2 EP 2063880 A2 EP2063880 A2 EP 2063880A2 EP 07823842 A EP07823842 A EP 07823842A EP 07823842 A EP07823842 A EP 07823842A EP 2063880 A2 EP2063880 A2 EP 2063880A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- lysine
- poly
- acid
- oleic acid
- composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 38
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 title claims abstract description 18
- 238000011282 treatment Methods 0.000 title description 10
- 229920000656 polylysine Polymers 0.000 claims abstract description 24
- 108010039918 Polylysine Proteins 0.000 claims abstract description 22
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 10
- 239000000194 fatty acid Substances 0.000 claims abstract description 10
- 229930195729 fatty acid Natural products 0.000 claims abstract description 10
- 150000004665 fatty acids Chemical class 0.000 claims abstract description 10
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 9
- 235000006708 antioxidants Nutrition 0.000 claims abstract description 9
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 6
- 229920000729 poly(L-lysine) polymer Polymers 0.000 claims description 102
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 39
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 39
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 39
- 239000005642 Oleic acid Substances 0.000 claims description 39
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 39
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 39
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims description 16
- XOAAWQZATWQOTB-UHFFFAOYSA-N Taurine Natural products NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 11
- 229960003080 taurine Drugs 0.000 claims description 8
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 6
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Natural products SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 6
- 239000004201 L-cysteine Substances 0.000 claims description 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Natural products C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 6
- 235000013878 L-cysteine Nutrition 0.000 claims description 4
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 claims description 4
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- 229960005070 ascorbic acid Drugs 0.000 claims description 4
- 239000011668 ascorbic acid Substances 0.000 claims description 4
- 235000012000 cholesterol Nutrition 0.000 claims description 4
- 229940099418 d- alpha-tocopherol succinate Drugs 0.000 claims description 4
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- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 claims description 4
- 235000019136 lipoic acid Nutrition 0.000 claims description 4
- 229930002330 retinoic acid Natural products 0.000 claims description 4
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- 229960001727 tretinoin Drugs 0.000 claims description 4
- 150000003862 amino acid derivatives Chemical class 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
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- QYPPJABKJHAVHS-UHFFFAOYSA-N Agmatine Natural products NCCCCNC(N)=N QYPPJABKJHAVHS-UHFFFAOYSA-N 0.000 claims description 2
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 claims description 2
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
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- 229940055726 pantothenic acid Drugs 0.000 claims description 2
- GHOKWGTUZJEAQD-ZETCQYMHSA-N pantothenic acid Natural products OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 claims description 2
- 235000019161 pantothenic acid Nutrition 0.000 claims description 2
- 239000011713 pantothenic acid Substances 0.000 claims description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 18
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- 241001465754 Metazoa Species 0.000 description 11
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- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 6
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N biotin Natural products N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 5
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- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 4
- IPCSVZSSVZVIGE-UHFFFAOYSA-N n-hexadecanoic acid Natural products CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 4
- FFEARJCKVFRZRR-UHFFFAOYSA-N L-Methionine Natural products CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 3
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- SECPZKHBENQXJG-FPLPWBNLSA-N (Z)-Palmitoleic acid Natural products CCCCCC\C=C/CCCCCCCC(O)=O SECPZKHBENQXJG-FPLPWBNLSA-N 0.000 description 2
- TZHFFNMXKPLNME-YFKPBYRVSA-N 5-[(2R)-2-amino-3-sulfanylpropanoyl]oxy-5-oxopentanoic acid Chemical compound C(CCCC(=O)O)(=O)OC([C@@H](N)CS)=O TZHFFNMXKPLNME-YFKPBYRVSA-N 0.000 description 2
- ULXRNYCUWLSGRN-ZETCQYMHSA-N 5-[(2S)-2-amino-4-methylsulfanylbutanoyl]oxy-5-oxopentanoic acid Chemical compound C(CCCC(=O)O)(=O)OC([C@@H](N)CCSC)=O ULXRNYCUWLSGRN-ZETCQYMHSA-N 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 2
- IELOKBJPULMYRW-NJQVLOCASA-N D-alpha-Tocopheryl Acid Succinate Chemical compound OC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C IELOKBJPULMYRW-NJQVLOCASA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 239000005639 Lauric acid Substances 0.000 description 2
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- 235000021360 Myristic acid Nutrition 0.000 description 2
- TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Natural products CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 2
- 235000021319 Palmitoleic acid Nutrition 0.000 description 2
- SYSLNQMKLROGCL-BCYUYYMPSA-N S-[(2E,6E)-farnesyl]-L-cysteine zwitterion Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CSC[C@H](N)C(O)=O SYSLNQMKLROGCL-BCYUYYMPSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
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- SECPZKHBENQXJG-UHFFFAOYSA-N cis-palmitoleic acid Natural products CCCCCCC=CCCCCCCCC(O)=O SECPZKHBENQXJG-UHFFFAOYSA-N 0.000 description 2
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- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N methyl undecanoic acid Natural products CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
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- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/203—Retinoic acids ; Salts thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
Definitions
- the present invention relates to a composition for controlling the evolution of Amyotrophic Lateral Sclerosis, comprising endogenous molecules grafted to Poly-Lysine, also known as Poly-Lysine conjugates.
- the invention also relates to the use of this composition.
- Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disease linked to the progressive impairment of motor neurons, nerve cells that control voluntary muscles. The impairment concerns both the peripheral motor neurons, in direct relation to the muscles, and the central motor neurons located in the motor cortex. This systematised degeneration of motor neurons results in numerous motor disorders such as the existence of spasms related to an exaggeration of muscle tone, an increase in osteo-tendinous reflexes, fasciculations, or paralysis associated with muscle atrophy.
- the bulbar form is related to the initial involvement of motor neurons of the brainstem and causes speech and swallowing disorders.
- Amyotrophic Lateral Sclerosis that starts with the motor neuron involvement of the motor cortex.
- the disease always evolves towards a complete form, with multiple disabilities that influence the vital prognosis.
- death is due to a respiratory deficiency aggravated by a bronchial superinfection.
- Amyotrophic lateral sclerosis The management of patients is limited to the prevention of motor dysfunction, the use of disabilities and the treatment of the symptoms of the disease. In addition, this care requires the intervention of professionals and requires hospitalization and special monitoring, heavy for patients.
- Amyotrophic able to control the progression of the disease and easy to administer.
- composition for controlling the evolution of amyotrophic lateral sclerosis comprising at least:
- the invention also proposes a particular composition capable of controlling the evolution of amyotrophic lateral sclerosis.
- the invention is now described in detail, with reference to the appended figures in which:
- FIG. 1 represents the curve of the mean normalized weight in grams of transgenic hSOD1 rats, obtained for three treatments: Dosel, Dose2 and Placebo,
- FIG. 2 represents the survival curve in days of hSOD1 transgenic rats treated with Dosel, Dose2 or placebo,
- FIG. 3 represents the follow-up over time of the Rotarod score (exercise time) in seconds, of hSOD1 transgenic rats treated with Dosel, Dose2 or placebo, and
- FIG. 4 represents the evolution of the mV amplitude of the muscular potential evoked over time, of hSOD1 transgenic rats treated with Dosel, Dose2 or placebo.
- the present invention aims at the use of a composition for the manufacture of a medicament for controlling the evolution of amyotrophic lateral sclerosis, the composition comprising at least:
- Antioxidants are the known antioxidants and free radical scavengers.
- the useful composition according to the invention comprises at least:
- Poly-Lysine is Poly-L-Lysine.
- the mechanism causing lateral sclerosis is unknown to date
- Amyotrophic It is known only that sporadic forms, without any mutation, coexist with much rarer familial forms, associated with mutations in the SOD1 gene coding for superoxide dismutase. Although we do not know the exact origin of the pathology, different hypotheses have been put forward to explain the motor neuron involvement. These hypotheses refer to several mechanisms, in particular oxidative stress, ie disorders of oxygen metabolism.
- ROS toxic reactive oxygen species
- NO nitric oxide
- Nitric oxide and EOR in general, present in large quantities, have deleterious actions on the body. They are responsible for changes in the elements of the self, namely amino acids, proteins and fatty acids. In particular, they cause oxidation of thiols, fatty acids and DNA nucleic acids involved in the death of motor neurons. Neuronal death is also linked to the phenomenon of excitotoxicity, which is based on the excessive mobilization of calcium in the cell as a result of activation of glutamate receptors. These disorders of calcium metabolism induce mitochondrial abnormalities that are also involved in oxidative metabolism. In people with Amyotrophic Lateral Sclerosis, there is a multiplicity of very aggressive radical mechanisms that lead to the death of motor neurons.
- An object of the present invention is therefore to fight against the formation of multiple free radicals involved in the disease and to control the oxidative processes induced so as to limit the destruction of motor neurons.
- the useful composition according to the invention contains a great diversity of free anti-free radicals conjugated to Poly-Lysine which trap the oxygenated species and inhibit the pathogenic oxidative processes.
- the pathology is linked to an unknown causal agent. This bacterial or viral environmental stress would trigger the production of antibodies against the constituents of these bacteria or viruses. The immune response induced would be involved in the death of motor neurons.
- circulating antibodies in patients with lateral sclerosis are associated with a great diversity of free anti-free radicals conjugated to Poly-Lysine which trap the oxygenated species and inhibit the pathogenic oxidative processes.
- Amyotrophic is particularly found antibodies against short-chain fatty acids.
- composition according to the invention contains poly-Lysine-conjugated fatty acids, in particular short-chain fatty acids which play a decoying role for the short-chain fatty acids carried by the potential causative agent of Amyotrophic Lateral Sclerosis.
- Lateral Amyotrophic is a multifactorial disease linked to a number of identified mechanisms.
- An objective of the invention is therefore to act on these different mechanisms and to combine the actions.
- composition according to the invention contains at least two types of endogenous molecules which have complementary and combined actions which allow to act on different aspects of lateral sclerosis
- the composition according to the invention contains at least three types of endogenous molecules.
- the molecules of the composition according to the invention can not be used unbound because they would be rapidly metabolized, would not reach their target and have no therapeutic activity.
- these endogenous molecules are grafted to a particular vector: Poly-Lysine. This particular vector makes it possible: to avoid the metabolic degradation of the endogenous molecules,
- Poly-Lysine also has the advantage of being inert, non-allergenic, non-immunogenic and having a long half-life.
- the composition according to the invention contains only endogenous substances that is known to be naturally present in the living. It has no toxicity or side effects and can be administered in the long term.
- the composition according to the invention can be incorporated into different types of pharmaceutical preparations presented in all galenic forms.
- compositions according to the invention there may be mentioned a particular composition containing the following poly-L-Lysine conjugates: - Oleic Acid - Poly-L-Lysine - Thioctic Acid
- the operating procedure consists in injecting daily from J65 to J185, subcutaneously, 500 ⁇ l of the composition according to the invention, Dosel or Dose2, or a placebo.
- concentrations in M (moles / liter) of the elements of the Dosel composition are as follows:
- Dose2 are as follows:
- the rats are approximately 65 days old.
- Blood samples are taken by venipuncture at the rat's tail at D60, D90, D115, D140, D225 and at the time of sacrifice at the end of the experiment.
- the weight of the animals is listed at least once a week.
- the weight curve makes it possible to detect directly whether an animal is developing muscle atrophy and therefore a loss of mass.
- the curve of the average of the normalized weights obtained for each of the three treatments is shown in FIG. 1. It is noted that the animals treated with the composition according to the invention (Dosel, Dose2) have an improved weight curve compared with the treated animals. by the placebo. Moreover, the survival of the animals is observed during the protocol.
- the survival curve according to the treatment, presented in FIG. 2 shows that the survival of the rats treated with the composition according to the invention (Dosel, Dose2) is significantly increased compared with that of the placebo-treated animals.
- the average survival time of the animals treated with the placebo is 210 days, while that of the animals treated with Dose 1 is 230 and with Dose 2 of 248.
- electromyographic tests are carried out on each animal at several periods: before inclusion in the protocol and during the protocol to
- J140 and J200 J140 and J200.
- Several parameters are measured, notably the amplitude of the muscular potential evoked in the muscles of the anterior-leggings box.
- results presented in FIG. 4 show that the rats treated with the composition according to the invention with Dose2 retain, on day 200, an amplitude greater than that of the animals treated with placebo.
- composition according to the invention has a beneficial effect on transgenic rats hSOD1, Sclerosis model.
- the invention is obviously not limited to the use of this example of the composition shown and described above, but covers all variants, especially with regard to fatty acids, antioxidants and the amino acid derivatives used, as well as preparations that may include the composition.
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Abstract
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0653789A FR2905868B1 (fr) | 2006-09-18 | 2006-09-18 | Composition destinee au traitement de la sclerose laterale amyotrophique |
PCT/FR2007/051947 WO2008035001A2 (fr) | 2006-09-18 | 2007-09-17 | Composition destinee au traitement de la sclerose laterale amyotrophique |
Publications (1)
Publication Number | Publication Date |
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EP2063880A2 true EP2063880A2 (fr) | 2009-06-03 |
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ID=37907089
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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EP07823842A Withdrawn EP2063880A2 (fr) | 2006-09-18 | 2007-09-17 | Composition destinee au traitement de la sclerose laterale amyotrophique |
Country Status (6)
Country | Link |
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US (1) | US20090318384A1 (fr) |
EP (1) | EP2063880A2 (fr) |
JP (1) | JP2010503645A (fr) |
CA (1) | CA2663272A1 (fr) |
FR (1) | FR2905868B1 (fr) |
WO (1) | WO2008035001A2 (fr) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
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EP3072513A1 (fr) * | 2015-03-26 | 2016-09-28 | Medday | Biotin pour le traitement de la sclérose latérale amyotrophique |
FR3048616B1 (fr) | 2016-03-14 | 2018-04-06 | Polyneuros | Polycomplexes de composes poly-lysine pour la prevention et/ou la lutte contre la sclerose laterale amyotrophique |
FR3066393B1 (fr) | 2017-05-16 | 2019-07-19 | Polyneuros | Principe actif constitue par un melange de composes poly-lysine et utilisation dans la prevention des avc et le traitement de la phase inflammatoire post-avc |
FR3122573B1 (fr) * | 2021-05-10 | 2024-03-29 | Hydro Fill Tech | Compositions de conjugués poly-lysine et de micelles et/ou de copolymères de poly-lysine |
FR3122571B1 (fr) * | 2021-05-10 | 2023-05-12 | Hydro Fill Tech | Compositions et leur utilisation pour rétablir la perméabilité intestinale et/ou prévenir ou lutter contre des maladies multifactorielles |
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FR2727117A1 (fr) * | 1994-11-18 | 1996-05-24 | Geffard Michel | Utilisation de conjugues de la polylysine pour la preparation de medicaments utiles dans le traitement des maladies neurodegeneratives et des affections degeneratives a caractere autoimmun |
US5788962A (en) * | 1995-01-17 | 1998-08-04 | The Curators Of The University Of Missouri | DNA sequences coding for mycoplasma hyopneumoniae surface antigens, corresponding proteins and use in vaccines and diagnostic procedures |
FR2886153B1 (fr) * | 2005-05-27 | 2009-04-10 | Gemac Sa | Composition destinee au traitement de la sclerose en plaques |
-
2006
- 2006-09-18 FR FR0653789A patent/FR2905868B1/fr not_active Expired - Fee Related
-
2007
- 2007-09-17 WO PCT/FR2007/051947 patent/WO2008035001A2/fr active Application Filing
- 2007-09-17 EP EP07823842A patent/EP2063880A2/fr not_active Withdrawn
- 2007-09-17 JP JP2009527873A patent/JP2010503645A/ja active Pending
- 2007-09-17 CA CA002663272A patent/CA2663272A1/fr not_active Abandoned
- 2007-09-17 US US12/441,808 patent/US20090318384A1/en not_active Abandoned
Non-Patent Citations (1)
Title |
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See references of WO2008035001A2 * |
Also Published As
Publication number | Publication date |
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JP2010503645A (ja) | 2010-02-04 |
FR2905868B1 (fr) | 2012-12-21 |
US20090318384A1 (en) | 2009-12-24 |
WO2008035001A3 (fr) | 2008-05-22 |
WO2008035001A2 (fr) | 2008-03-27 |
CA2663272A1 (fr) | 2008-03-27 |
FR2905868A1 (fr) | 2008-03-21 |
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