| Novel use of peptide compounds for treating amyotrophic lateral sclerosis -> Monitor Keywords |
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Novel use of peptide compounds for treating amyotrophic lateral sclerosisRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Peptide Containing (e.g., Protein, Peptones, Fibrinogen, Etc.) Doai, Cyclopeptides, 2 Peptide Repeating Units In Known Peptide ChainNovel use of peptide compounds for treating amyotrophic lateral sclerosis description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20050277596, Novel use of peptide compounds for treating amyotrophic lateral sclerosis. Brief Patent Description - Full Patent Description - Patent Application Claims
[0001] The present invention is directed to the use of a class of peptide compounds for treating amyotrophic lateral sclerosis (ALS) and other forms of motoneuron diseases and peripheral neuropathies. [0002] Certain peptides are known to exhibit central nervous system (CNS) activity and are useful in the treatment of epilepsy and other CNS disorders. These peptides which are described in the U.S. Pat. No. 5,378,729 have the Formula (Ia): 1 [0003] wherein [0004] R is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl, aryl lower alkyl, heterocyclic, heterocyclic lower alkyl, lower alkyl heterocyclic, lower cycloalkyl, lower cycloalkyl lower alkyl, and R is unsubstituted or is substituted with at least one electron withdrawing group or electron donating group; [0005] R.sub.1 is hydrogen or lower alkyl, lower alkenyl, lower alkynyl, aryl lower alkyl, aryl, heterocyclic lower alkyl, heterocyclic, lower cycloalkyl, lower cycloalkyl lower alkyl, each unsubstituted or substituted with an electron donating group or an electron withdrawing group; and [0006] R.sub.2 and R.sub.3 are independently hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl lower alkyl, aryl, heterocyclic, heterocyclic lower alkyl, lower alkyl heterocyclic, lower cycloalkyl, lower cycloalkyl lower alkyl, or Z-Y wherein R.sub.2 and R.sub.3 may be unsubstituted or substituted with at least one electron withdrawing group or electron donating group; [0007] Z is O, S, S(O).sub.a, NR.sub.4, PR.sub.4 or a chemical bond; [0008] Y is hydrogen, lower alkyl, aryl, aryl lower alkyl, lower alkenyl, lower alkynyl, halo, heterocyclic, heterocyclic lower alkyl, and Y may be unsubstituted or substituted with an electron donating group or an electron withdrawing group, provided that when Y is halo, Z is a chemical bond, or [0009] ZY taken together is NR.sub.4NR.sub.5R.sub.7, NR.sub.4O.sub.5, ONR.sub.4R.sub.7, OPR.sub.4R.sub.5, PR.sub.4OR.sub.5, SNR.sub.4R.sub.7, NR.sub.4SR.sub.7, SPR.sub.4R.sub.5 or PR.sub.4SR.sub.7, NR.sub.4PR.sub.5R.sub.6 or PR.sub.4NR.sub.5R.sub.7, 2 [0010] R.sub.4, R.sub.5 and R.sub.6 are independently hydrogen, lower alkyl, aryl, aryl lower alkyl, lower alkenyl, or lower alkynyl, wherein R.sub.4, R.sub.5 and R.sub.6 may be unsubstituted or substituted with an electron withdrawing group or an electron donating group; and [0011] R.sub.7is R.sub.6 or COOR.sub.8 or CON; [0012] R.sub.8 is hydrogen or lower alkyl, or aryl lower alkyl, and the aryl or alkyl group may be unsubstituted or substituted with an electron withdrawing group or an electron donating group; and [0013] n is 1-4; and [0014] a is 1-3. [0015] U.S. Pat. No. 5,773,475 also discloses additional compounds useful for treating CNS disorders. These compounds are N-benzyl-2-amino-3-methox- y-propionamide having the Formula (IIa): 3 [0016] wherein [0017] Ar is aryl which is unsubstituted or substituted with halo; R.sub.3 is lower alkoxy; and R.sub.1 is methyl. [0018] The patents U.S. Pat. No. 5,378,729 and U.S. Pat. No. 5,773,475 are hereby incorporated by reference. However, neither of these patents describes the use of these compounds as specific neuroprotective agents for the treatment of ALS and other motoneuron diseases as well as peripheral neuropathies. [0019] WO 02/074297 relates to the use of a compound according to Formula (IIa) wherein Ar is phenyl which may be substituted by at least one halo, R.sub.3 is lower alkoxy containing 1-3 carbon atoms and R.sub.1 is methyl for the preparation of pharmaceutical compositions useful for the treatment of allodynia related to peripheral neuropathic pain. [0020] WO 02/074784 relates to the use of a compound having Formula (Ia) or/and Formula (IIa) showing antinociceptive properties for treating different types and symptoms of acute and chronic pain, especially non neuropathic inflammatory pain, e.g. rheumatoid arthritic pain or/and secondary inflammatory osteo-arthritic pain. [0021] Amyotrophic lateral sclerosis is characterized by degeneration and loss of motoneurons in the anterior horn of the spinal cord and of the brainstem and, to a variable extent, by degeneration of the descending motor pathways within the cortico-spinal tract (Deng et al., 1993; Rothstein et al., 1995). This disorder leads to progressive muscular atrophy, weakness, paralysis and eventually death due to respiratory failure (Andersen et al., 1995). ALS occurs in both familial (FALS) and sporadic (SALS) forms. FALS accounts for 5-10% of cases, with an autosomal dominant pattern of inheritance (Gurney et al., 1994; Rosen et al., 1993). Approximately 20% of the FALS cases have been associated with mutations in SOD1, the gene that encodes for cytosolic Cu,Zn superoxide dismutase (SOD) (Beckman et al., 1993; Rosen et al., 1993). This recent discovery of mutations affecting the SOD gene has given impetus to research on the role of oxidative stress in the pathogenesis of FALS. [0022] In order to establish an animal model for familial ALS, several strains of transgenic mice that carry the human SOD1 gene have been produced. Mice overproducing wild-type human Cu,Zn SOD are clinically normal and in fact show increased resistance to oxidative stress (Yang et al., 1994). Mice producing mutant Cu,Zn SOD rapidly develop a progressive motoneuron disease that strongly resembles ALS (Gurney et al., 1994; Mohajeri et al., 1998). This phenotype occurs in mice expressing the G93A mutation as well as a glycine.fwdarw.arginine mutation (Gurney et al., 1994). [0023] The mechanisms of motoneuron disorders are poorly understood. Current treatments use a variety of pharmacological, surgical, physical and psychological approaches. However, the evidence for many of the treatments is still limited. [0024] The use of compounds of Formula (Ib) or/and Formula (IIb) for treatment of motoneuron disorders has not been reported. Thus, the present invention concerns the use of said compounds of Formulae (Ib) or/and (IIb) for the preparation of a pharmaceutical composition for the prevention, alleviation or/and treatment of motoneuron disorders such as ALS, progressive spinal muscular atrophies or progressive bulbar palsy, or/and peripheral neuropathies such as Guillain-Barr Syndrome or Charcot-Marie-Tooth Syndrome. Continue reading about Novel use of peptide compounds for treating amyotrophic lateral sclerosis... 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