WO2023009537A1 - Use of mesenchymal stem cells in treatment of juvenile hypoplastic left heart syndrome - Google Patents

Use of mesenchymal stem cells in treatment of juvenile hypoplastic left heart syndrome Download PDF

Info

Publication number
WO2023009537A1
WO2023009537A1 PCT/US2022/038370 US2022038370W WO2023009537A1 WO 2023009537 A1 WO2023009537 A1 WO 2023009537A1 US 2022038370 W US2022038370 W US 2022038370W WO 2023009537 A1 WO2023009537 A1 WO 2023009537A1
Authority
WO
WIPO (PCT)
Prior art keywords
patient
administration
change
stem cells
mesenchymal stem
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.)
Ceased
Application number
PCT/US2022/038370
Other languages
English (en)
French (fr)
Inventor
Joshua M. Hare
Sunjay Kaushal
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Longeveron Inc
Original Assignee
Longeveron 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 Longeveron Inc filed Critical Longeveron Inc
Priority to JP2024504874A priority Critical patent/JP2024527034A/ja
Priority to CN202280062443.6A priority patent/CN117999082A/zh
Priority to EP22758316.8A priority patent/EP4376950A1/en
Priority to KR1020247006241A priority patent/KR20240040776A/ko
Priority to AU2022316959A priority patent/AU2022316959A1/en
Priority to CA3227475A priority patent/CA3227475A1/en
Priority to US18/292,150 priority patent/US20240350549A1/en
Publication of WO2023009537A1 publication Critical patent/WO2023009537A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/02—Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
    • A61B5/026—Measuring blood flow
    • A61B5/029—Measuring blood output from the heart, e.g. minute volume
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/48—Other medical applications
    • A61B5/4836—Diagnosis combined with treatment in closed-loop systems or methods
    • A61B5/4839—Diagnosis combined with treatment in closed-loop systems or methods combined with drug delivery
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Definitions

  • the following disclosure contains methods of treatment for HLHS, the methods comprising administering a composition of mesenchymal stem cells (MSC) to a subject in need of HLHS treatment.
  • MSC mesenchymal stem cells
  • FIG. 12 depicts the change in tricuspid regurgitation net aortic forward flow for select patients throughout the course of a clinical study.
  • FIG. 13 depicts the change in tricuspid regurgitation for each patient throughout the course of a clinical study.
  • FIG. 14 depicts a comparison between the post-treatment survival rate of patients who were administered Lomecel-BTM cells for treatment of HLHS and patients who underwent the clinical study performed by Son, et al. for treatment of HLHS.
  • MSCs secrete numerous bioactive molecules that: stimulate endogenous stem cell recruitment, proliferation, and differentiation; inhibit apoptosis and fibrosis; and stimulate neovascularization. MSCs can also regulate host stem cell niches through cell-cell interactions. Thus, MSCs can enhance intrinsic repair and regenerative mechanisms.
  • FIG. 4 depicts the right ventricular end-diastolic volume changes for each patient throughout the course of the clinical study. Measurements were taken at the beginning of the clinical study, six months post administration and twelve months post administration. The data presented within FIG. 4 was indexed to the BSA of the patients. Table 7 contains MRI data used to determine the change in each patient’s right ventricular end-diastolic volume after administration of the Lomecel-BTM cells.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Cardiology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Cell Biology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Virology (AREA)
  • Epidemiology (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Pathology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Surgery (AREA)
  • Physiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
PCT/US2022/038370 2021-07-26 2022-07-26 Use of mesenchymal stem cells in treatment of juvenile hypoplastic left heart syndrome Ceased WO2023009537A1 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
JP2024504874A JP2024527034A (ja) 2021-07-26 2022-07-26 若年性左心低形成症候群の治療における間葉系幹細胞の使用
CN202280062443.6A CN117999082A (zh) 2021-07-26 2022-07-26 间充质干细胞在治疗青少年左心发育不良综合征中的用途
EP22758316.8A EP4376950A1 (en) 2021-07-26 2022-07-26 Use of mesenchymal stem cells in treatment of juvenile hypoplastic left heart syndrome
KR1020247006241A KR20240040776A (ko) 2021-07-26 2022-07-26 소아 좌심 형성부전 증후군의 치료에 있어서의 중간엽 줄기 세포의 용도
AU2022316959A AU2022316959A1 (en) 2021-07-26 2022-07-26 Use of mesenchymal stem cells in treatment of juvenile hypoplastic left heart syndrome
CA3227475A CA3227475A1 (en) 2021-07-26 2022-07-26 Use of mesenchymal stem cells in treatment of juvenile hypoplastic left heart syndrome
US18/292,150 US20240350549A1 (en) 2021-07-26 2022-07-26 Use of Mesenchymal Stem Cells in Treatment of Juvenile Hypoplastic Left Heart Syndrome

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202163203519P 2021-07-26 2021-07-26
US63/203,519 2021-07-26

Publications (1)

Publication Number Publication Date
WO2023009537A1 true WO2023009537A1 (en) 2023-02-02

Family

ID=83049982

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2022/038370 Ceased WO2023009537A1 (en) 2021-07-26 2022-07-26 Use of mesenchymal stem cells in treatment of juvenile hypoplastic left heart syndrome

Country Status (9)

Country Link
US (1) US20240350549A1 (https=)
EP (1) EP4376950A1 (https=)
JP (1) JP2024527034A (https=)
KR (1) KR20240040776A (https=)
CN (1) CN117999082A (https=)
AU (1) AU2022316959A1 (https=)
CA (1) CA3227475A1 (https=)
TW (1) TW202321437A (https=)
WO (1) WO2023009537A1 (https=)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2025062365A1 (en) * 2023-09-22 2025-03-27 Mesoblast International Sárl Mesenchymal lineage precursor or stem cells (mlpscs) for use in methods of treating congenital heart disease

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20190038742A1 (en) 2016-02-04 2019-02-07 Longeveron Llc Mesenchymal stem cells as vaccine adjuvants and methods for using the same
US20190290698A1 (en) 2016-11-11 2019-09-26 Longeveron Llc Methods of Using Human Mesenchymal Stem Cells to Effect Cellular and Humoral Immunity
US20200129558A1 (en) 2017-06-19 2020-04-30 Longeveron Llc Treatment of sexual dysfunction and improvement in sexual quality of life
WO2021061203A1 (en) * 2019-09-24 2021-04-01 Mezzion Pharma Co., Ltd. Methods of improving exercise performance, single ventricular performance, and myocardial performance index (mpi) in single ventricle heart disease, using udenafil compositions

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20190038742A1 (en) 2016-02-04 2019-02-07 Longeveron Llc Mesenchymal stem cells as vaccine adjuvants and methods for using the same
US20190290698A1 (en) 2016-11-11 2019-09-26 Longeveron Llc Methods of Using Human Mesenchymal Stem Cells to Effect Cellular and Humoral Immunity
US20200129558A1 (en) 2017-06-19 2020-04-30 Longeveron Llc Treatment of sexual dysfunction and improvement in sexual quality of life
WO2021061203A1 (en) * 2019-09-24 2021-04-01 Mezzion Pharma Co., Ltd. Methods of improving exercise performance, single ventricular performance, and myocardial performance index (mpi) in single ventricle heart disease, using udenafil compositions

Non-Patent Citations (24)

* Cited by examiner, † Cited by third party
Title
A. R. WILLIAMS ET AL.: "Enhanced effect of combining human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and to restore cardiac function after myocardial infarction", CIRCULATION, vol. 127, no. 2, 2013, pages 213 - 223, XP055253561, DOI: 10.1161/CIRCULATIONAHA.112.131110
A. R. WILLIAMS ET AL.: "Intramyocardial stem cell injection in patients with ischemic cardiomyopathy: functional recovery and reverse remodeling", CIRC RES, vol. 108, no. 7, 2011, pages 792 - 796
ALABDULGADER: "Survival analysis: prenatal vs. postnatal diagnosis of HLHS", J INVASIVE NONINVASIVE CARDIOL, vol. 1, 2018, pages 8 - 12
BARRON ET AL.: "Hypoplastic left heart syndrome", THE LANCET, vol. 374, no. 9689, 2009, pages 551 - 564, XP026467951, DOI: 10.1016/S0140-6736(09)60563-8
CAO ET AL.: "S-nitrosoglutathione reductase-dependent PPARgamma denitrosylation participates in MSC-derived adipogenesis and osteogenesis", J CLIN INVEST, vol. 125, no. 4, 2015, pages 1679 - 1691
HATZISTERGOS ET AL.: "Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation", CIRC RES, vol. 107, no. 7, 2010, pages 913 - 922, XP055255062, DOI: 10.1161/CIRCRESAHA.110.222703
HATZISTERGOS ET AL.: "Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease", CIRC RES, vol. 109, no. 8, 2011, pages 923 - 940, XP055054593, DOI: 10.1161/CIRCRESAHA.111.243147
HOFFMAN JESSICA R ET AL: "Computational Modelling of Mesenchymal Stem Cell Exosomes Predicts Cardiac Improvements in Preclinical and Clinical Models of Hypoplastic Left Heart Syndrome; ISEV2020 Abstract Book, OF15.3", J EXTRACELL VESICLES. 2020; 9(SUPPL 1): 1784511., 15 July 2020 (2020-07-15), pages 63 - 63, XP055979270, Retrieved from the Internet <URL:https://onlinelibrary.wiley.com/doi/10.1080/20013078.2020.1784511> [retrieved on 20221108], DOI: 10.1080/20013078.2020.1784511 *
KAUSHAL ET AL.: "Study design and rationale for ELPIS: A phase I/Ilb randomized pilot study of allogeneic human mesenchymal stem cell injection in patients with hypoplastic left heart syndrome", AMERICAN HEART JOURNAL, vol. 192, 2017, pages 48 - 56
KAUSHAL SUNJAY ET AL: "Study design and rationale for ELPIS: A phase I/IIb randomized pilot study of allogeneic human mesenchymal stem cell injection in patients with hypoplastic left heart syndrome", AMERICAN HEART JOURNAL, vol. 192, 27 June 2017 (2017-06-27), AMSTERDAM, NL, pages 48 - 56, XP055979232, ISSN: 0002-8703, DOI: 10.1016/j.ahj.2017.06.009 *
KELLEHERLAUSSENTEIXEIRA-PINTODUGGAN: "Growth and correlates of nutritional status among infants with hypoplastic left heart syndrome (HLHS) after stage 1 Norwood procedure", NUTRITION, vol. 22, no. 3, 2006, pages 237 - 244
KONACKERSONLO: "How pediatricians counsel parents when no best-choice management exists: lessons to be learned from hypoplastic left heart syndrome", ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE, vol. 158, no. 5, 2004, pages 436 - 441
LE BLANC ET AL.: "Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study", LANCET, vol. 371, no. 9624, 2008, pages 1579 - 1586, XP026859188, DOI: 10.1016/S0140-6736(08)60690-X
MAHLESPRAYWERNOVSKYGAYNORCLARK III: "Survival after reconstructive surgery for hypoplastic left heart syndrome: a 15-year experience from a single institution", CIRCULATION, 2000
MALLIARASKREKEMARBAN: "The stuttering progress of cell therapy for heart disease", CLIN PHARMACOL THER, vol. 90, no. 4, 2011, pages 532 - 541
MASCIO ET AL.: "Thirty years and 1663 consecutive Norwood procedures: has survival plateaued?", J THORAC CARDIOVASC SURG, vol. 158, no. 1, 2019, pages 220 - 229, XP085725786, DOI: 10.1016/j.jtcvs.2018.12.117
MORRIS ET AL.: "Prenatal diagnosis, birth location, surgical center, and neonatal mortality in infants with hypoplastic left heart syndrome", CIRCULATION, vol. 129, no. 3, 2014, pages 285 - 292
OHYE, R. G. ET AL.: "Comparison of shunt types in the Norwood procedure for single-ventricle lesions", NEW ENGLAND JOURNAL OF MEDICINE, vol. 362, no. 21, 2010, pages 1980 - 1992
ROSENMYERBURGFRANCISCOLEMARBAN: "Translating stem cell research to cardiac disease therapies: pitfalls and prospects for improvement", J AM COLL CARDIOL, vol. 64, no. 9, 2014, pages 922 - 937
RYCHIK, J.: "Hypoplastic left heart syndrome: from in-utero diagnosis to school age", PAPER PRESENTED AT THE SEMINARS IN FETAL AND NEONATAL MEDICINE, 2005
SIFFELRIEHLE-COLARUSSOOSTERCORREA: "Survival of Children With Hypoplastic Left Heart Syndrome", PEDIATRICS, vol. 136, no. 4, 2015, pages e864 - 870
SON ET AL.: "Prognostic value of serial echocardiography in hypoplastic left heart syndrome", CIRCULATION: CARDIOVASCULAR IMAGING, vol. 11, no. 7, 2018, pages e006983
TOEBBEYEHLEKIRKPATRICKCODDINGTON: "Hypoplastic left heart syndrome: parent support for early decision making", JOURNAL OF PEDIATRIC NURSING, vol. 28, no. 4, 2013, pages 383 - 392
WEHMAN ET AL.: "Mesenchymal stem cells preserve neonatal right ventricular function in a porcine model of pressure overload", AM J PHYSIOL HEART CIRC PHYSIOL, vol. 310, no. 11, 2016, pages 816 - 1826

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2025062365A1 (en) * 2023-09-22 2025-03-27 Mesoblast International Sárl Mesenchymal lineage precursor or stem cells (mlpscs) for use in methods of treating congenital heart disease

Also Published As

Publication number Publication date
TW202321437A (zh) 2023-06-01
KR20240040776A (ko) 2024-03-28
CN117999082A (zh) 2024-05-07
AU2022316959A1 (en) 2024-02-29
EP4376950A1 (en) 2024-06-05
CA3227475A1 (en) 2023-02-02
JP2024527034A (ja) 2024-07-19
US20240350549A1 (en) 2024-10-24

Similar Documents

Publication Publication Date Title
Rupp et al. Intracoronary bone marrow cell application for terminal heart failure in children
Tuma et al. Safety and feasibility of percutaneous retrograde coronary sinus delivery of autologous bone marrow mononuclear cell transplantation in patients with chronic refractory angina
Tarui et al. Stem cell therapies in patients with single ventricle physiology
Povsic et al. Epicardial delivery of XC001 gene therapy for refractory angina coronary treatment (The EXACT Trial): Rationale, design, and clinical considerations
US20240350549A1 (en) Use of Mesenchymal Stem Cells in Treatment of Juvenile Hypoplastic Left Heart Syndrome
CN104862281A (zh) 表达bFGF和PDGF-BB的重组载体修饰的间充质干细胞及其制备方法和用途
Weale et al. Adult congenital heart disease
Haller et al. Surgical strategies in single ventricle management of neonates and infants
Qureshi et al. Cell-based therapy for myocardial dysfunction after fontan operation in hypoplastic left heart syndrome
US20190224240A1 (en) Cell therapy for the treatment of non-ischemic heart failure
Wehman et al. Stem cell therapy for CHD: towards translation
HK40103434A (zh) 间充质干细胞在治疗青少年左心发育不良综合征中的用途
Tabbah et al. Surviving a single ventricle and a single atrium with a situs inversus viscerum
CN113425731B (zh) 一种增效干细胞治疗心梗的药物及其应用
Ristić-Andjelkov et al. Left ventricular noncompaction in a patient presenting with a left ventricular failure
Juan et al. Two cases of anomalous origin of left coronary artery from the pulmonary artery
Weale et al. Adult congenital heart disease
Qiu et al. Congenital atresia of the left main coronary artery with left ventricular noncompaction: From infancy to adulthood
Lācis MEDICINE & NUTRACEUTICAL RESEARCH
Shah et al. EARLY OUTCOMES OF TOTAL CORRECTION IN TETRALOGY OF FALLOT IN A TERTIARY CARE HOSPITAL OF PESHAWAR, KHYBER PAKHTUNKHWA, PAKISTAN; A TWO-YEAR RETROSPECTIVE STUDY.
Sheu et al. Six-month angiographic study of immediate autologous bone marrow mononuclear cell implantation on acute anterior wall myocardial infarction using a mini-pig model
Selvan et al. Long-term follow-up of persistent truncus arteriosus: Kuwait experience
Ristić-AnĎelkov et al. PRESENTING WITH A LEFT VENTRICULAR FAIILURE NEKOMPAKTNA LEVA KOMORA KAO UZROK SRČANE SLABOSTI
Barbukhatty et al. A rare case of coronary artery bypass grafting in a patient with left ventricular noncompaction
Lacy-Niebla et al. Surgical treatment of intracardiac teratoma in a 66 years-old man. Case report

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22758316

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2024504874

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 3227475

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: AU2022316959

Country of ref document: AU

ENP Entry into the national phase

Ref document number: 20247006241

Country of ref document: KR

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 1020247006241

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: 2022758316

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2022316959

Country of ref document: AU

Date of ref document: 20220726

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 2022758316

Country of ref document: EP

Effective date: 20240226

WWE Wipo information: entry into national phase

Ref document number: 202280062443.6

Country of ref document: CN