MX2019000327A - Regímenes de dosificación de antagonistas de lingo-1 y usos para el tratamiento de trastornos desmielinizantes. - Google Patents

Regímenes de dosificación de antagonistas de lingo-1 y usos para el tratamiento de trastornos desmielinizantes.

Info

Publication number
MX2019000327A
MX2019000327A MX2019000327A MX2019000327A MX2019000327A MX 2019000327 A MX2019000327 A MX 2019000327A MX 2019000327 A MX2019000327 A MX 2019000327A MX 2019000327 A MX2019000327 A MX 2019000327A MX 2019000327 A MX2019000327 A MX 2019000327A
Authority
MX
Mexico
Prior art keywords
lingo
antagonists
treatment
dosage regimens
demyelinating disorders
Prior art date
Application number
MX2019000327A
Other languages
English (en)
Inventor
Cadavid Diego
Xu Lei
Xu Lin
Original Assignee
Biogen Ma Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Biogen Ma Inc filed Critical Biogen Ma Inc
Publication of MX2019000327A publication Critical patent/MX2019000327A/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6854—Immunoglobulins
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/28—Neurological disorders
    • G01N2800/285—Demyelinating diseases; Multipel sclerosis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biochemistry (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Microbiology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biotechnology (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Endocrinology (AREA)
  • Mycology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Dermatology (AREA)

Abstract

Se describen regímenes de dosificación, métodos, composiciones y kits para detectar y/o tratar una enfermedad desmielinizante del SNC.
MX2019000327A 2016-07-13 2017-07-12 Regímenes de dosificación de antagonistas de lingo-1 y usos para el tratamiento de trastornos desmielinizantes. MX2019000327A (es)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US201662362032P 2016-07-13 2016-07-13
US201662394094P 2016-09-13 2016-09-13
US201662412582P 2016-10-25 2016-10-25
US201762486217P 2017-04-17 2017-04-17
US201762512510P 2017-05-30 2017-05-30
PCT/US2017/041757 WO2018013714A1 (en) 2016-07-13 2017-07-12 Dosage regimens of lingo-1 antagonists and uses for treatment of demyelinating disorders

Publications (1)

Publication Number Publication Date
MX2019000327A true MX2019000327A (es) 2019-04-11

Family

ID=59388180

Family Applications (1)

Application Number Title Priority Date Filing Date
MX2019000327A MX2019000327A (es) 2016-07-13 2017-07-12 Regímenes de dosificación de antagonistas de lingo-1 y usos para el tratamiento de trastornos desmielinizantes.

Country Status (16)

Country Link
US (2) US20200031924A1 (es)
EP (1) EP3484512A1 (es)
JP (1) JP7149257B2 (es)
KR (1) KR20190039134A (es)
CN (1) CN109862911A (es)
AU (1) AU2017297404A1 (es)
BR (1) BR112019000630A2 (es)
CA (1) CA3030745A1 (es)
CL (1) CL2019000027A1 (es)
CO (1) CO2019001116A2 (es)
IL (1) IL264139A (es)
MA (1) MA45668A (es)
MX (1) MX2019000327A (es)
PH (1) PH12019500075A1 (es)
SG (1) SG11201811704SA (es)
WO (1) WO2018013714A1 (es)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
UY38605A (es) * 2019-03-11 2020-09-30 Biogen Ma Inc Composiciones farmacéuticas que contienen anticuerpos anti-lingo-1
CN116549632B (zh) * 2023-03-28 2024-09-10 中国人民解放军军事科学院军事医学研究院 抗Lingo-1抗体Opicinumab的新用途及针对新用途的药物
CN116740064B (zh) * 2023-08-14 2023-10-20 山东奥洛瑞医疗科技有限公司 一种核磁共振肿瘤区域提取方法

Family Cites Families (55)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
JPS6147500A (ja) 1984-08-15 1986-03-07 Res Dev Corp Of Japan キメラモノクロ−ナル抗体及びその製造法
EP0173494A3 (en) 1984-08-27 1987-11-25 The Board Of Trustees Of The Leland Stanford Junior University Chimeric receptors by dna splicing and expression
GB8422238D0 (en) 1984-09-03 1984-10-10 Neuberger M S Chimeric proteins
JPS61134325A (ja) 1984-12-04 1986-06-21 Teijin Ltd ハイブリツド抗体遺伝子の発現方法
GB2183662B (en) 1985-04-01 1989-01-25 Celltech Ltd Transformed myeloma cell-line and a process for the expression of a gene coding for a eukaryotic polypeptide employing same
GB8601597D0 (en) 1986-01-23 1986-02-26 Wilson R H Nucleotide sequences
GB8607679D0 (en) 1986-03-27 1986-04-30 Winter G P Recombinant dna product
US5225539A (en) 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
US5116742A (en) 1986-12-03 1992-05-26 University Patents, Inc. RNA ribozyme restriction endoribonucleases and methods
US4987071A (en) 1986-12-03 1991-01-22 University Patents, Inc. RNA ribozyme polymerases, dephosphorylases, restriction endoribonucleases and methods
GB8717430D0 (en) 1987-07-23 1987-08-26 Celltech Ltd Recombinant dna product
AU4308689A (en) 1988-09-02 1990-04-02 Protein Engineering Corporation Generation and selection of recombinant varied binding proteins
US5223409A (en) 1988-09-02 1993-06-29 Protein Engineering Corp. Directed evolution of novel binding proteins
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
WO1991000906A1 (en) 1989-07-12 1991-01-24 Genetics Institute, Inc. Chimeric and transgenic animals capable of producing human antibodies
JP3068180B2 (ja) 1990-01-12 2000-07-24 アブジェニックス インコーポレイテッド 異種抗体の生成
US5427908A (en) 1990-05-01 1995-06-27 Affymax Technologies N.V. Recombinant library screening methods
AU665190B2 (en) 1990-07-10 1995-12-21 Cambridge Antibody Technology Limited Methods for producing members of specific binding pairs
GB9015198D0 (en) 1990-07-10 1990-08-29 Brien Caroline J O Binding substance
ATE352612T1 (de) 1990-08-29 2007-02-15 Pharming Intellectual Pty Bv Homologe rekombination in säugetier-zellen
ATE158021T1 (de) 1990-08-29 1997-09-15 Genpharm Int Produktion und nützung nicht-menschliche transgentiere zur produktion heterologe antikörper
DK0564531T3 (da) 1990-12-03 1998-09-28 Genentech Inc Berigelsesfremgangsmåde for variantproteiner med ændrede bindingsegenskaber
ATE363532T1 (de) 1991-03-01 2007-06-15 Dyax Corp Verfahren zur herstellung bindender miniproteine
ES2315612T3 (es) 1991-04-10 2009-04-01 The Scripps Research Institute Genotecas de receptores heterodimericos usando fagemidos.
DE69233482T2 (de) 1991-05-17 2006-01-12 Merck & Co., Inc. Verfahren zur Verminderung der Immunogenität der variablen Antikörperdomänen
DE4122599C2 (de) 1991-07-08 1993-11-11 Deutsches Krebsforsch Phagemid zum Screenen von Antikörpern
MX9204374A (es) 1991-07-25 1993-03-01 Idec Pharma Corp Anticuerpo recombinante y metodo para su produccion.
WO1994004678A1 (en) 1992-08-21 1994-03-03 Casterman Cecile Immunoglobulins devoid of light chains
US5736137A (en) 1992-11-13 1998-04-07 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma
EP0669986B1 (en) 1992-11-13 2003-04-09 Idec Pharmaceuticals Corporation Fully impaired consensus kozac sequences for mammalian expression
DK0678122T3 (da) 1993-01-12 2000-03-06 Biogen Inc Rekombinante anti-VLA4 antistofmolekyler
AU687790B2 (en) 1993-02-09 1998-03-05 Biogen Idec Ma Inc. Treatment for insulin dependent diabetes
US5840299A (en) 1994-01-25 1998-11-24 Athena Neurosciences, Inc. Humanized antibodies against leukocyte adhesion molecule VLA-4
GB9524973D0 (en) 1995-12-06 1996-02-07 Lynxvale Ltd Viral vectors
US20030143204A1 (en) 2001-07-27 2003-07-31 Lewis David L. Inhibition of RNA function by delivery of inhibitors to animal cells
PL191251B1 (pl) 1997-03-14 2006-04-28 Idec Pharma Corp Sposób wprowadzania żądanego DNA w docelowe miejsce w genomie ssaka i układ wektorów
AU2001245793A1 (en) 2000-03-16 2001-09-24 Cold Spring Harbor Laboratory Methods and compositions for rna interference
JP5133494B2 (ja) 2001-08-10 2013-01-30 アバディーン ユニバーシティ 抗原結合ドメイン
US20030157641A1 (en) 2001-11-16 2003-08-21 Idec Pharmaceuticals Corporation Polycistronic expression of antibodies
US20030166282A1 (en) 2002-02-01 2003-09-04 David Brown High potency siRNAS for reducing the expression of target genes
US7556944B2 (en) 2002-05-03 2009-07-07 The Board Of Trustees Of The Leland Stanford Junior University Methods and compositions for use in preparing siRNAs
US7700758B2 (en) 2002-08-12 2010-04-20 New England Biolabs, Inc. Methods and compositions relating to gene silencing
PL1606409T3 (pl) 2003-03-19 2011-02-28 Biogen Ma Inc Białko wiążące receptor Nogo
CN1972707B (zh) * 2004-06-24 2014-12-03 比奥根艾迪克Ma公司 涉及脱髓鞘的疾病的治疗
JP4960865B2 (ja) 2004-06-24 2012-06-27 バイオジェン・アイデック・エムエイ・インコーポレイテッド 脱髄に関連する状態の処置
CN103351437A (zh) * 2006-11-17 2013-10-16 诺瓦提斯公司 Lingo结合分子及其制药用途
WO2008086006A2 (en) * 2007-01-09 2008-07-17 Biogen Idec Ma Inc. Sp35 antibodies and uses thereof
US8128926B2 (en) 2007-01-09 2012-03-06 Biogen Idec Ma Inc. Sp35 antibodies and uses thereof
EP2205071B1 (en) * 2007-10-11 2015-07-22 Biogen MA Inc. Lingo-1 antagonists and trkb agonists for use in the treatment of glaucoma
CA2729961C (en) 2008-07-09 2018-05-01 Biogen Idec Ma Inc. Li113, li62 variant co2, anti-lingo antibodies
IT1395574B1 (it) 2009-09-14 2012-10-16 Guala Dispensing Spa Dispositivo di erogazione
SG191875A1 (en) 2011-02-07 2013-08-30 Biogen Idec Inc S1p modulating agents
KR102257645B1 (ko) * 2012-10-09 2021-06-01 바이오젠 엠에이 인코포레이티드 탈수초성 질환의 치료를 위한 복합 요법 및 용도
CA2973266A1 (en) * 2015-01-08 2016-07-14 Biogen Ma Inc. Lingo-1 antagonists and uses for treatment of demyelinating disorders

Also Published As

Publication number Publication date
AU2017297404A1 (en) 2019-01-24
KR20190039134A (ko) 2019-04-10
CO2019001116A2 (es) 2019-02-19
US20200031924A1 (en) 2020-01-30
BR112019000630A2 (pt) 2019-07-09
US20210403556A1 (en) 2021-12-30
EP3484512A1 (en) 2019-05-22
CL2019000027A1 (es) 2019-05-24
MA45668A (fr) 2019-05-22
PH12019500075A1 (en) 2019-07-08
CN109862911A (zh) 2019-06-07
JP2019524731A (ja) 2019-09-05
JP7149257B2 (ja) 2022-10-06
WO2018013714A1 (en) 2018-01-18
IL264139A (en) 2019-02-28
CA3030745A1 (en) 2018-01-18
SG11201811704SA (en) 2019-01-30

Similar Documents

Publication Publication Date Title
MX2023004593A (es) Inhibidores de tirosina cinasa 2 (tyk2) y usos de los mismos.
PH12019500095A1 (en) Compounds, compositions, and methods for the treatment of disease
PH12018500086A1 (en) Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases
MX2017009038A (es) Antagonistas de proteina 1 de interacción con el receptor de nogo que contiene el dominio de inmunoglobulina y repeticiones ricas en leucina (lingo-1) y usos para el tratamiento de trastornos desmielinizantes.
MX2020012165A (es) Derivados de bencimidazol como inhibidores de tirosina cinasa erbb para el tratamiento del cancer.
GEP20247593B (en) Compositions and methods of inhibiting masp-3 for the treatment of various diseases and disorders
MX2017014191A (es) Metodos de tratamiento de una enfermedad neurodegenerativa.
NZ737399A (en) Ccr2 modulators
MX2018006632A (es) Inhibidores biciclicos de peptidilarginina deiminasa 4 (pad4).
NZ735044A (en) Condensed ring derivative, and preparation method, intermediate, pharmaceutical composition and use thereof
MX2017011206A (es) Combinacion de un antagonista con muerte programada 1 (pd-1) y eribulina para el tratamiento de cancer.
TW201713341A (en) Compositions and methods of treating a neurodegenerative disease
TN2017000196A1 (en) 4-oxo-3,4-dihydro-1,2,3-benzotriazines as modulators of gpr139
EA201791227A1 (ru) РЕЖИМ ДОЗИРОВАНИЯ АНТАГОНИСТОВ MAdCAM
PH12019500075A1 (en) Dosage regimens of lingo-1 antagonists and uses for treatment of demyelinating disorders
MX2018005987A (es) Compuestos heterociclicos para el tratamiento de enfermedades.
MX2021006011A (es) Un inhibidor de la quinasa aurora a para su uso en el tratamiento del neuroblastoma.
MX2018009662A (es) Metodo y composicion farmaceutica para tratamiento de neurodegeneracion.
MX2018001592A (es) Composiciones y metodos para el tratamiento y la prevencion de trastornos neurodegenerativos.
MX370897B (es) Compuestos bicíclicos fusionados para el tratamiento de enfermedades,.
EA201692482A1 (ru) Способы лечения заболеваний антителами, которые связывают рецептор колониестимулирующего фактора 1 (csf1r)
MX2018014034A (es) Compuestos bicíclicos fusionados para el tratamiento de enfermedades.
EA201790851A1 (ru) Способы предотвращения, уменьшения и лечения макулодистрофии
MX2017002093A (es) Terapia con anticuerpos para vih como sustituto de tratamiento.
PH12016502480A1 (en) Compounds, pharmaceutical composition and their use in treating neurodegenerative diseases