WO2021195438A1 - Traitement de lésions respiratoires - Google Patents

Traitement de lésions respiratoires Download PDF

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WO2021195438A1
WO2021195438A1 PCT/US2021/024243 US2021024243W WO2021195438A1 WO 2021195438 A1 WO2021195438 A1 WO 2021195438A1 US 2021024243 W US2021024243 W US 2021024243W WO 2021195438 A1 WO2021195438 A1 WO 2021195438A1
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PCT/US2021/024243
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Bradley Robinson
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Predictive Technology Group, Inc.
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/48—Reproductive organs
    • A61K35/51—Umbilical cord; Umbilical cord blood; Umbilical stem cells
    • A—HUMAN NECESSITIES
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    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
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    • A61K38/19—Cytokines; Lymphokines; Interferons
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    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/21—Interferons [IFN]
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    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
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Definitions

  • Viral infection can lead to severe complications, such as lung damage, in subjects if left untreated or if treatment is ineffective.
  • development of traditional antiviral regimens can be labor-intensive and costly and may not be beneficial in all cases.
  • mutation of viruses can hinder development of effective antiviral therapies and/or reduce the efficacy of a treatment over time in a population.
  • New approaches for the treatment of viral infections are needed.
  • a method for treating one or more symptoms in a subject comprises: administering a therapeutically effective amount of allogenic stem cells to the subject to treat the one or more symptoms, wherein (i) the one or more symptoms comprise respiratory damage, (ii) the allogenic stem cells are from at least in part Wharton’s jelly, and (iii) the allogenic stem cells are administered in a formulation in unit dose form.
  • the one or more symptoms are at least in part produced from or occurring as a result of a viral infection.
  • the one or more symptoms are at least in part produced from or occurring as a result of a non-viral cause.
  • the subject has emphysema.
  • the allogenic stem cells comprise mesenchymal stem cells (MSCs).
  • the MSCs are not expanded in vitro.
  • the MSCs express CD73, CD90, CD105, or any combination thereof.
  • the MSCs do not substantially express CD14, CD34, CD45, HLA-DR, CD 19, or any combination thereof.
  • the allogenic stem cells are harvested mechanically.
  • the administering is performed during onset of a viral infection. In some cases, the administering is performed after onset of a viral infection. In some cases, the administering is performed before and after onset of a viral infection.
  • the method further comprises administering to the subject remdesivir, chloroquine, lopinavir, ritonavir, favilavir, corticosteroid, interferon-beta, antivirals, vitamin C, a salt thereof, or any combination thereof.
  • the method further comprises administering to the subject oxygen, saline, or any combination thereof.
  • the method further comprises administering to the subject azithromycin, amoxicillin, cephalosporin, fluroquinolone, ampicillin, sulbactam, doxycycline, an antibiotic, a salt of any of these, or any combination thereof.
  • the herb comprises two or more herbs, extracts thereof, or any combinations thereof in a traditional Chinese medicine formulation.
  • the subject is a human subject.
  • the human subject is about 1 month to about 12 months old, 1 year to about 20 years, 15 years to about 50 years, 40 years to about 80 years, or about 60 years to about 110 years.
  • the human subject has a comorbidity.
  • the comorbidity is selected from schematic heart disease, hypertension, atrial fibrillation, stroke, renal failure, liver disease, cancer, diabetes, respiratory disease or any combination thereof.
  • comorbidity is a respiratory disease selected from asthma, chronic obstructive pulmonary disease, bronchitis, emphysema, lung cancer, cystic fibrosis, pneumonia, pleural effusion, or any combination thereof.
  • the subject is a smoker.
  • the treating comprises administering a solid formulation to the subject.
  • the solid formulation is a powder.
  • the solid formulation comprises one or more of remdesivir, chloroquine, lopinavir, ritonavir, favilavir, corticosteroid, interferon-beta, antivirals, vitamin C, azithromycin, amoxicillin, cephalosporin, fluroquinolone, ampicillin, sulbactam, doxycycline, an antibiotic, saline, an herb, an herb extract, a salt of any of these, or a combination thereof.
  • the therapeutically effective amount of the allogenic stem cell is formulated as a liquid formulation.
  • the liquid formulation is administered by intravenous injection, by inhalation, or a combination thereof.
  • the therapeutically effective amount comprises an amount of about 0.1 ⁇ 10 6 cells per kilogram of weight, an amount of 0.1 ⁇ 10 6 cells per kilogram of weight to 1 ⁇ 10 6 cells per kilogram of weight, an amount of about 1 ⁇ 10 6 cells per kilogram of weight, an amount of 1 ⁇ 10 6 cells per kilogram of weight to 5 ⁇ 10 6 cells per kilogram of weight, an amount of about 5 ⁇ 10 6 cells per kilogram of weight, an amount of 5 ⁇ 10 6 cells per kilogram of weight to 10 ⁇ 10 6 cells per kilogram of weight, an amount of about 10 ⁇ 10 6 cells per kilogram of weight, an amount of 10 ⁇ 10 6 cells per kilogram of weight, an amount of 10 x 10 6 cells per kilogram of weight to 20 ⁇ 10 6 cells per kilogram of weight, an amount of about 20 x 10 6 cells per kilogram of weight, an amount of 20 ⁇ 10 6 cells per kilogram of weight to 100 x 10 6 cells per kilogram of weight, an amount of about 100 ⁇ 10 6 cells per kilogram of weight, or an amount greater than 100 ⁇ 10 6 cells per kilogram of weight.
  • the administering is performed at least once per day, at least twice per day, at least three times per day, or at least 4 times per day. In some cases, the administering is performed for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months 11 months, 1 year, 2 years, 3 years, at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months at least 11 months, at least 1 year, at least 2 years, at least 3 years, 1 day to 2 days, 2 days to 3 days, 1 day
  • the allogenic stem cells are harvested mechanically.
  • the respiratory damage comprises lung damage, trouble breathing, inflammation, shortness of breath, a cough, wheezing, a productive cough comprising blood, a productive cough comprising mucus, discolored fingernails, decreased blood oxygen level, chest tightness of any combination thereof.
  • the viral infection is diagnosed with an antibody diagnostic, quantitative polymerase chain reaction (PCR), real-time reverse transcription PCR, PCR, an enzyme-linked immunosorbent assay (ELISA), a rapid diagnostic test, an imaging method, a general symptom, or any combination thereof.
  • the imaging method is an X-ray, computed tomography (CT) scan, a magnetic resonance image (MRI), an ultrasound, or any combination thereof.
  • the general symptom is a fever, a cough, a shortness of breath, breathing difficulties, or any combination thereof.
  • the administering the therapeutically effective amount of allogenic stem cells results in a change in the respiratory damage.
  • a change in the respiratory damage following the administration of the therapeutically effective amount of allogenic stem cells comprises an increased blood oxygen level, reduced cough, decreased wheezing, normal fingernail color, an improved respiratory image relative to an image taken during infection but before administration of stem cells, or any combination thereof.
  • the change in the respiratory damage results in at least a partially amelioration of the respiratory damage.
  • treatment with the therapeutically effective amount of the allogenic stem cell results in a reduction of inflammation.
  • the reduction of inflammation comprises decreased fluid accumulation, reduced swelling, decreased immobility, reduced accumulation of lymphocytes, or any combination thereof.
  • the reduction of inflammation comprises decreased TNF-alpha concentration, decreased C-reactive protein concentration, a decreased quantity of overactivated cytokine-secreting immune cells or any combination thereof in the bloodstream of the human.
  • the overactivated cytokine-secreting immune cells are T-cells.
  • the allosteric stem cells are administered with at least one of the following: fetuin-A, interleukin 37, macrophage colony stimulating factor, serpin A4, syndecan-4, complement component 5a, platelet derived growth factor-AA, thrombospondin-2, adhesion G protein, cystatin-B, galectin- 9, granulysin, lipocalin-2, intracellular adhesion molecule 1.
  • fetuin-A interleukin 37
  • macrophage colony stimulating factor serpin A4
  • syndecan-4 complement component 5a
  • platelet derived growth factor-AA thrombospondin-2
  • adhesion G protein adhesion G protein
  • cystatin-B galectin- 9, granulysin, lipocalin-2
  • intracellular adhesion molecule 1 intracellular adhesion molecule 1.
  • the viral load is a Coronavirus viral load.
  • the formulation comprises an excipient.
  • the excipient is Wharton’s jelly, saline, or any combination thereof.
  • the unit dose formulation is contained within a vial.
  • the unit dose formulation is stored as a cryogenic composition.
  • the cryogenic composition contains a cryoprotectant.
  • the cryoprotectant comprises Wharton’s Jelly and saline.
  • the viral infection is from the virus SAR-CoV-2 (COVID-19), SARS-COV, MERS-CoV, HKU1, OC43, NL63, 229E or any combination thereof.
  • the virus comprises a Coronavirus or a mutated form thereof.
  • the virus comprises SAR-CoV-2 (COVID-19) or a mutated form thereof.
  • Methods and compositions disclosed herein include treatments and methods of treating subjects having one or more symptoms related to respiratory damage and/or viral infection. In some cases, methods and systems described herein can be used to treat a subject having one or more symptoms associated with and/or caused by a viral infection.
  • administering e.g., stem cells, such as mesenchymal stem cells (MSCs)
  • one or more additional agents described herein e.g., an antibiotic, an antiviral medication, a steroid, or a corticosteroid
  • administration of one or more cells e.g., stem cells, such as mesenchymal stem cells (MSCs)
  • one or more additional agents described herein e.g., an antibiotic, an antiviral medication, a steroid, or a corticosteroid
  • a subject having one or more symptoms associated with a condition having a non-viral cause can be treated using the methods and/or compositions described herein.
  • administering e.g., stem cells, such as mesenchymal stem cells (MSCs)
  • MSCs mesenchymal stem cells
  • additional agents described herein e.g., an antibiotic, an antiviral medication, a steroid, or a corticosteroid
  • administering can partially or completely ameliorate the one or more symptoms of the respiratory damage.
  • a treatment described herein can comprise one or more allogenic stem cells (e.g., one or more allogenic mesenchymal stem cells (MSCs)). Allogeneic stem cells can be derived from a donor and can be given to a different recipient of the cells. Allogenic stem cells can be undifferentiated cells and can multiply by cell division. Allogenic stem cells can divide indefinitely and can generate many different cell types.
  • a treatment described herein can comprise one or more autologous cells (e.g., one or more autologous stem cells, such as mesenchymal stem cells (MSCs).
  • one or more autologous cells can be administered to a subject for treating one or more conditions or symptoms described herein (e.g., viral infection, emphysema, lung damage, etc.).
  • a mesenchymal stem cell MSC
  • MSC mesenchymal stem cell
  • one or more allogenic cells can be administered to a subject for treating one or more conditions or symptoms described herein (e.g., viral infection, emphysema, lung damage, etc.).
  • MSCs can be of the stromal origin and may differentiate into different types of tissues and cell types, for example, a MSC can differentiate into an osteoblast, a chondroblast, an adipocyte, a myocyte, a neuroectodermal cell, or a hepatocyte. MSCs can be isolated from an umbilical cord, a placenta, an adipose tissue, a lung, teeth, bone marrow, Wharton’s jelly or any combination thereof.
  • a method described herein can comprise differentiating one or more stem cells (e.g., one or more MSCs for administration to a subject) toward a cellular lineage (e.g., wherein the cellular lineage is selected from: ectodermal, endodermal, mesodermal or wherein the cellular lineage is selected from osteoblast, chondroblast, adipocyte, myocyte, neuroectodermal, or hepatocyte).
  • stem cells e.g., one or more MSCs for administration to a subject
  • a cellular lineage e.g., wherein the cellular lineage is selected from: ectodermal, endodermal, mesodermal or wherein the cellular lineage is selected from osteoblast, chondroblast, adipocyte, myocyte, neuroectodermal, or hepatocyte.
  • one or more stem cells can be differentiated in culture (e.g., in vitro culture, which may comprise adherent culture on culture plastic, such as tissue culture plastic or culture plastic comprising one or more extracellular matrix proteins, and/or culturing in a bioreactor).
  • one or more stem cells e.g., one or more MSCs
  • can be differentiated via non-adherent expansion e.g., via embryoid body formation.
  • a method described herein can comprise isolating cells grown ex vivo (e.g., cells grown in culture in vitro). In some cases, cells are not cultured or expanded in vitro.
  • one or more cells can be formulated for administration to a subject after isolation (e.g., dissociation from a tissue, for example via mechanical mincing of the tissue), for example, without culturing the cells between isolation and administration.
  • MSCs can be used in clinical therapy to modulate the immune response, provide tropic support, regenerate damaged tissue, or any combination thereof.
  • Wharton’s Jelly may be a biological matrix, comprising collagen and glucosaminoglycans, and found in umbilical cords. Wharton’s Jelly can be harvested by enzymatic or mechanical methods.
  • the jelly may comprise various cell types, mucopolysaccharides, proteins, glycoproteins, growth factors, cytokines or any combination thereof.
  • Wharton’s Jelly can include an epithelial cell, an epidermal cell, a fibroblast, an immune cell, a stem cell or any combination thereof.
  • Wharton’s Jelly can be a rich source of MSCs. In some cases, Wharton’s Jelly can contain up to 20% MSC.
  • viable MSCs can be isolated from different sources, for example, an umbilical cord, with a tissue mincer, a chemical, an enzymatic, a mechanical disruption or any combination thereof.
  • an MSC can be a primary cell or an immortalized cell (e.g., an immortalized MSC).
  • mechanical disruption may be a tissue mincer.
  • the use of a tissue mincer can comprise using a manual tissue mincer (e.g., a pair of scissors) or a mechanical tissue mincer (e.g., an automatic tissue mincer, such as a tissue homogenizer).
  • a mechanical disruption can reduce the solid tissue of the umbilical cord to pieces of between about 0.1 grams to about 10 grams.
  • the umbilical cord tissue pieces can be combined with an amount of saline, at a ratio of grams tissue: milliliters saline of from about 1 : 100 to about 1 :2, in one embodiment about 1 gram of tissue can be combined with about 5 ml of saline (i.e. 1:5).
  • the saline can be a solution ofNaCl of between 0.1 and 23%, in one embodiment, the saline can be about a 0.9% solution.
  • the Wharton’s Jelly may be subjected to further processing after processing with the tissue mincer.
  • the Wharton’s Jelly can be separated from solid tissue and other larger pieces of umbilical cord by filtering through, for example, a filter of at least about 100 micrometer ( ⁇ m) pore size filter.
  • the Wharton’s Jelly can be filtered through a filter having a pore size less than about 100 ⁇ m, 95 ⁇ m, 90 ⁇ m, 85 ⁇ m, 80 ⁇ m, 75 ⁇ m, 70 ⁇ m, 65 ⁇ m, 60 ⁇ m, 55 ⁇ m, 50 ⁇ m, 45 ⁇ m, 40 ⁇ m, 35 ⁇ m, 30 ⁇ m, 25 ⁇ m, 20 ⁇ m, 15 ⁇ m, 10 ⁇ m, or 5 ⁇ m, or greater than about 1 ⁇ m, 5 ⁇ m, 10 ⁇ m, 15 ⁇ m, 20 ⁇ m, 25 ⁇ m, 30 ⁇ m, 35 ⁇ m, 40 ⁇ m, 45 ⁇ m, 50 ⁇ m, 55 ⁇ m, 60 ⁇ m, 65
  • the Wharton’ s Jelly can comprise one or more of a mammalian cell, a protein, a peptide, and an extracellular matrix.
  • the Wharton’s Jelly can comprise a population ofMSCs at a concentration of between about 0.1 ⁇ 10 6 cells/mL and 20 ⁇ 10 6 cells/mL,
  • the Wharton’s Jelly can comprise about 5-40% MSCs of the total population of cells, in some embodiments the amount of MSCs in Wharton’s Jelly, relative to all the cells, can be about 20%.
  • MSCs can express CD73, CD90, CD105, or any combination thereof.
  • MSCs can express TNF- ⁇ receptor type 1.
  • one or more MSCs may not substantially express CD11, CD 14, CD 19, CD34, CD45, HLA-DR, or any combination thereof (e.g., wherein the one or more MSCs express CD11, CD 14, CD 19, CD34, CD45, and/or HLA-DR at a level that is statistically similar to and/or does not have a higher median level of expression than a control cell population, such as a cell population known to express phenotypically insignificant levels of the marker(s)).
  • viable MSCs are plastic adherent.
  • a population of cells can be positive for a specific marker if between about 30% and 100% of the cells express the marker, for example, greater than about 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%, and less than about 100%, 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, or 35%.
  • a population of cells can be negative for a specific marker if between about 70% and 0% of the cells express the marker, for example less than about 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, or 5%, and greater than about 0%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, or 65%.
  • a positive marker can be expressed by more than 80% of the population and a negative marker can be expressed by less than about 20% of the population.
  • a cell that may be negative for a given marker can have a level of staining that may be above zero, but less than what may be deemed the level of background for a given ceil with a given marker.
  • the MSCs are not expanded in vitro.
  • expansion e.g., culture
  • expansion of all or a portion of a population ofMSCs used in a treatment described herein in vitro has been disallowed.
  • the MSCs can be cryopreserved. In some embodiments, cryopreservation can occur at temperatures less than about -20 °C to greater than about -140 °C. In some embodiments, cryopreservation can include a composition. In some embodiments, the cryopreservation compositions may include a concentration of DMSO between about 0% to about 30%, a concentration of human serum albumin between about 0.1 and about 10%, or any combination thereof. In some embodiments, the cryopreservation composition can include saline, Wharton’s jelly, or any combination thereof. In some embodiments, the cryopreservation composition can include DMSO, albumin, saline, Wharton’s jelly, or any combination thereof. In some embodiments, the MSCs can be in a vial. In some embodiments, the vial can be glass, plastic, metal, or any combination thereof.
  • administer can refer to methods that can be used to enable delivery of MSCs or MSCs formulations to the desired site of biological action. Delivery can include direct application to the affect tissue or region of the body. Delivery can include a parenchymal injection, an intra-thecal injection, an intra-ventricular injection, or an intra-ci sternal injection. A composition provided herein can be administered by any method.
  • a method of administration can be by intravenous injection, intraarterial injection, intracerebroventricular injection, intraci sternal injection, intramuscular injection, intraorbital injection, intraparenchymal injection, intraperitoneal injection, intraspinal injection, intrathecal injection, intraventricular injection, stereotactic injection, subcutaneous injection, or any combination thereof.
  • Delivery can include parenteral administration (including intravenous, subcutaneous, intrathecal, intraperitoneal, intramuscular, intravascular or infusion), oral administration, inhalation administration, intraduodenal administration, rectal administration.
  • delivery can include topical administration (such as a lotion, a cream, a gel, a liquid, a solid, a powder, an ointment) to an external surface of a surface, such as a skin.
  • a liquid formulation can be converted (e.g., dried, for example, by a process comprising freeze-drying or other means such as atomization) into a solid (e.g., a powder).
  • a treatment (e.g., which can be administered to a subject, such as a subject having or suspected of having a viral infection) comprises one or more MSCs and/or one or more additional agents, such as azithromycin, amoxicillin, cephalosporin, fluroquinolone, ampicillin, sulbactam, doxycycline, an antibiotic, remdesivir, chloroquine, lopinavir, ritonavir, favilavir, corticosteroid, interferon-beta, antivirals, vitamin C, a salt of any of these, or any combination.
  • additional agents such as azithromycin, amoxicillin, cephalosporin, fluroquinolone, ampicillin, sulbactam, doxycycline, an antibiotic, remdesivir, chloroquine, lopinavir, ritonavir, favilavir, corticosteroid, interferon-beta, antivirals, vitamin C
  • a treatment e.g., comprising one or more of azithromycin, amoxicillin, cephalosporin, fluroquinolone, ampicillin, sulbactam, doxycycline, an antibiotic, remdesivir, chloroquine, lopinavir, ritonavir, favilavir, corticosteroid, interferon-beta, antivirals, vitamin C, a salt of any of these, or any combination thereof
  • a lyophilized solid e.g., a lyophilized powder
  • a solid or powder formulation described herein can be hydrated or reconstituted at a desired concentration in a liquid to produce a liquid formulation (e.g., for injection or oral administration).
  • a solid or powder formulation described herein e.g., a lyophilized solid or lyophilized powder
  • a subject can administer the composition in the absence of supervision.
  • a subject can administer the composition under the supervision of a medical professional (e.g., a physician, nurse, physician’s assistant, orderly, hospice worker, or a combination thereof).
  • a medical professional can administer the composition.
  • treatment or “treating” of a viral infection can comprise causing a change in (e.g., reducing) the frequency or severity of symptoms.
  • treating a subject e.g., who has a viral infection
  • treatment of a viral infection can include, for example, relieving the cough experienced by a subject (e.g., a human male subject or a human female subject) having a viral infection (e.g., Coronavirus infection), or causing the regression or disappearance of a viral infection (e.g., a Coronavirus infection).
  • a subject e.g., a human male subject or a human female subject
  • a viral infection e.g., Coronavirus infection
  • treatment of a male subject can be different than treatment of a female subject having a same or similar viral infection (e.g., based on gender-related presentation of symptoms and/or gender-based response to treatment).
  • treatment can include an improved respiratory diagnostic image relative to a diagnostic image taken during infection but before administration of the stem cells.
  • treatment can reduce proinflammatory cytokines, for example, TNF- ⁇ , IL-Ib, IL-6, IL-2, IL-7, GSCF, IP10, MCP1, MIP1A, or any combination thereof.
  • treatment can reduce C-reactive protein.
  • treatment can reduce overactivated immune cells, for example, T-cells, macrophages, neutrophils, NK cells, peripheral blood mononuclear cells (PBMCs) or any combination thereof. Treating can also include: reduced malaise, cessation of viral infection side effects, abatement of a viral infection, or any combination thereof.
  • the MHCs can be administered during the infection. In some embodiments, the MHCs can be administered before the infection. In some embodiments, the MHCs can be administered after the infection. In some embodiments the MHCs can be administered before, during, and after an infection. In some embodiments representative daily intravenous, or injection dosages are from about 0.1 ⁇ 10 6 cells per kilogram of weight to about 1.
  • ⁇ 10 6 cells per kilogram of weight from about 1 ⁇ 10 6 cells per kilogram of weight to about 10 x 10 6 cells per kilogram of weight, from about 10 ⁇ 10 6 cells per kilogram of weight to about 100 x 10 6 cells per kilogram of weight, or from about 100 ⁇ 10 6 cells per kilogram of weight to about 1000 ⁇ 10 6 cells per kilogram of weight per day of the MSC.
  • ranges of dosage amounts represent total dosage amounts of the active ingredient per day for a given patient.
  • a daily administered dose can be less than about: 1000 ⁇ 10 6 cells per kilogram of weight, 100 ⁇ 10 6 cells per kilogram of weight, 10 ⁇ 10 6 cells per kilogram of weight, 1 ⁇ 10 6 cells per kilogram of weight, 0.1 ⁇ 10 6 cells per kilogram of weight, or 0.01 ⁇ 10 6 cells per kilogram of weight per day of the MSCs. In some embodiments, a daily administered dose can be at least about: 1000 ⁇ 10 6 cells per kilogram of weight, 100 ⁇ 10 6 cells per kilogram of weight, 10 ⁇ 10 6 cells per kilogram of weight, 1 ⁇ 10 6 cells per kilogram of weight, 0.1 ⁇ 10 6 cells per kilogram of weight, or 0.01 ⁇ 10 6 cells per kilogram of weight per day of the MSC.
  • the treatment can be given once, twice, three, or four times in a 24 hour period.
  • the treatment with MSC cells can last about or at least: 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days or 14 days.
  • the treatment with MSCs can last about or at least: 1 week, 2 weeks, 3 weeks, 4 weeks.
  • the treatment with MSCs can last about or at least: 1 year, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years or 10 years.
  • the treatment of MSCs can be administered with a second therapy that can comprise one or more agents selected from remdesivir, chloroquine, lopinavir, ritonavir, favilavir, corticosteroid, interferon-beta, antivirals, vitamin C, azithromycin, amoxicillin, cephalosporin, fluroquinolone, ampicillin, sulbactam, doxycycline, an antibiotic, an antifungal, an antimalarial, a salt of any of these, or any combination thereof.
  • the treatment of MSCs can be oxygen, intravenous saline, or any combination thereof.
  • a second therapy can comprise an anticancer drug, chemotherapy, radiation, a bone marrow transplantation, immunotherapy, a hormone therapy, a cryotherapy, a surgical procedure or any combination thereof.
  • a second therapy can comprise administration of a muscle relaxant, an anti-depressant, a steroid, an opioid, a cannabis-based therapeutic, acetaminophen, a non-steroidal anti-inflammatory, a neuropathic agent, a cannabis, a progestin, a progesterone, or any combination thereof.
  • a second therapy can include a non-steroidal anti- inflammatory can comprise naproxen, ibuprofen, a COX-2 inhibitor, or any combination thereof.
  • a second therapy can comprise administration of a biologic agent, cellular therapy, regenerative medicine therapy, a tissue engineering approach, a stem cell transplantation or any combination thereof.
  • a second therapy can comprise a medical procedure.
  • a second therapy can comprise an herb, an extract thereof of any combination thereof.
  • the herb or herb extract can be one of traditional Chinese medication, for example, astragalus, ginkgo biloba, red yeast rice, cinnamon, ginger, ginseng, goto kola, yu xing cao, monkshood rood, birth works, cayenne pepper, Chinese kabootar, cocklebur fruit, crow differ, croton seed, dioscorea root, rhubarb, cardamom fruit, thunder god vine, insects, fungi, marine life, minerals, mammals, reptiles, amphibians, or any combination thereof.
  • traditional Chinese medication for example, astragalus, ginkgo biloba, red yeast rice, cinnamon, ginger, ginseng, goto kola, yu xing cao, monkshood rood, birth works, cayenne pepper, Chinese kabootar, cocklebur fruit, crow differ, croton seed, dioscorea root, rhubarb, cardamom fruit,
  • a subject can be a human.
  • a subject can have or can be suspected of having a disease or condition.
  • the subject can be a patient, such as a patient being treated for a condition or a disease, such as a heart disease, hypertension, atrial fibrillation, stroke, renal failure, liver disease, cancer, diabetes, respiratory disease, asthma, chronic obstructive pulmonary disease, bronchitis, emphysema, lung cancer, cystic fibrosis, Coronavirus infection, pneumonia, pleural effusion or any combination thereof.
  • the subject can have one or more symptoms of respiratory damage.
  • respiratory damage can comprise lung damage, trouble breathing, inflammation, shortness of breath, a cough, wheezing, a productive cough comprising blood, a productive cough comprising mucus, discolored fingernails, decreased blood oxygen level, chest tightness, or any combination thereof.
  • the subject can have and/or be suspected of having and/or be at risk of having acute respiratory distress syndrome (ARDS).
  • ARDS can result from an inflammatory response in a subject’s body (e.g., in response to a viral infection).
  • ARDS can develop from a non-viral cause.
  • ARDS can arise from a condition such as emphysema, which can be caused by smoking.
  • a subject can be identified (e.g., alone or in combination with one or more additional indications, such as family history, a viral infection, and/or heart disease) as a candidate for treatment with one or more methods or compositions described herein on the basis of being a smoker (e.g., of tobacco products) or having a history of smoking.
  • ARDS can be caused by overactivated immune cells, such as overactivated T-cells.
  • ARDS can result from cytokine storm (e.g., which may result from a viral infection) and/or be identified by symptoms of cytokine storm in a subject (e.g., increased cytokine levels in the blood and/or increased activation of immune cells, such as immune cells in the blood).
  • ARDS can result in excess fluid accumulation in the lungs and/or damage to the lungs (e.g., resulting from fluid accumulation in the lungs).
  • the presence of ARDS in a subject can be determined via measurement of blood oxygenation and/or via imaging (e.g., X-ray imaging or computer tomography (CT) imaging).
  • CT computer tomography
  • a subject can be predisposed to a risk of developing a condition or a disease such as a respiratory disease.
  • a subject can be in remission from a condition or a disease, such as a cancer patient.
  • a subject can be healthy.
  • a composition or formulation can be a liquid, a solid, an aerosol, a powder, or any combination thereof.
  • the composition or formulation can include an excipient.
  • Excipients can include, but are not limited to one or more of: Wharton’s jelly, saline, water, a fluidizer, a lubricant, an adhesion agent, a surfactant, an acidifying agent, an alkalizing agent, an agent to adjust pH, an antimicrobial preservative, an antioxidant, an anti- static agent, a buffering agent, a chelating agent, a humectant, a gel-forming agent, or a wetting agent.
  • Excipients can also include a coloring agent, a coating agent, a sweetening agent, a flavoring and perfuming agent or a masking agent.
  • a composition and formulation can include a therapeutic agent with an individual excipient or with multiple excipients in any suitable combination, with or without a carrier.
  • a therapeutically effective amount can refer to the amount of MSCs with or without additional agents that can be effective to achieve its intended purpose. Individual patient needs may vary. Generally, the dosage required to provide an effective amount of the compound, salt thereof, or composition containing one or both of these, and which can be adjusted by one of ordinary skill in the art, will vary, depending on the age, health, physical condition, sex, weight, extent of the dysfunction of the recipient, frequency of treatment and the nature and scope of the dysfunction. Dosages can be in unit dose form.
  • administering MSCs as described herein can be used to prevent or treat diseases associated with or caused by a virus (e.g., a Coronavirus).
  • diseases can include, for example, a cough, a fever, malaise, myalgia, fatigue, difficult breathing, a runny nose, a sore throat, nasal congestion, a headache, diarrhea, acute respiratory distress syndrome (ARDS), a secondary infection or any combination thereof.
  • the secondary infection can be a bacterial infection, a viral infection, a fungal infection, an infectious disease, or any combination thereof.
  • a coronavirus infection can be caused by alpha coronavirus, beta coronavirus, gamma coronavirus, delta coronavirus, 229E coronavirus, NL63 coronavirus, OC43 coronavirus, HKU1 coronavirus, MERS-CoV, SARS-CoV, SARS-CoV-2 (COVID-19), or any combination of these.
  • a coronavirus infection can be diagnosed with an antibody diagnostic, polymerase chain reaction (PCR), quantitative polymerase chain reaction (qPCR), real-time reverse transcription PCR, an enzyme-linked immunosorbent assay (ELISA), a rapid diagnostic test, IgG, IgM, IgA, an imaging method, a general symptom or any combination thereof.
  • PCR polymerase chain reaction
  • qPCR quantitative polymerase chain reaction
  • ELISA enzyme-linked immunosorbent assay
  • the imaging method can be an X-ray, a computed tomography (CT) scan, a magnetic resonance image (MRI), an ultrasound, or any combination thereof.
  • CT computed tomography
  • MRI magnetic resonance image
  • ultrasound ultrasound
  • the general symptom can be a cough, shortness of breath, breathing difficulties, or a combination thereof.
  • administering MSCs as described herein can be used for patients with comorbidities.
  • comorbidities can include, for example, hypertension, pulmonary hypertension, congestive heart failure, renal failure, myocardial infraction, stable, unstable and variant (Prinzmetal) angina, atherosclerosis, cardiac edema, renal insufficiency, nephrotic edema, hepatic edema, stroke, asthma, bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, dementia including Alzheimer's disease, immunodeficiency, premature labor, Parkinson's disease, multiple sclerosis, dysmenorrhoea, benign prostatic hyperplasis (BPH), bladder outlet obstruction, incontinence, conditions of reduced blood vessel patency, e.g., postpercutaneous transluminal coronary angioplasty (post-PTCA), peripheral vascular disease, respiratory disease, bronchitis, emphysem
  • post-PTCA
  • a method of making a composition can comprise contacting a cell as described herein other ingredients as described herein (e.g. a carrier, diluent, excipient, etc.).

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Abstract

L'invention concerne des procédés de traitement d'un symptôme chez un être humain résultant au moins en partie produit d'une infection virale ou se produisant à partir d'une infection virale, comprenant : l'administration d'une quantité thérapeutiquement efficace de cellules souches allogéniques à un être humain pour traiter le symptôme.
PCT/US2021/024243 2020-03-25 2021-03-25 Traitement de lésions respiratoires WO2021195438A1 (fr)

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