U.S. patent application number 15/341471 was filed with the patent office on 2017-09-21 for treatment for chronic myocardial infarct.
The applicant listed for this patent is BioCardia, Inc.. Invention is credited to Peter A. Altman, Julio Argentieri, Luis M. de la Fuente, Eduardo Penaloza, Simon H. Stertzer.
Application Number | 20170266107 15/341471 |
Document ID | / |
Family ID | 40721901 |
Filed Date | 2017-09-21 |
United States Patent
Application |
20170266107 |
Kind Code |
A1 |
de la Fuente; Luis M. ; et
al. |
September 21, 2017 |
TREATMENT FOR CHRONIC MYOCARDIAL INFARCT
Abstract
A method of treating chronic post-myocardial infarction
including helical needle transendocardial delivery of autologous
bone marrow (ABM) mononuclear cells around regions of hypo or
akinesia in chronic post-myocardial infarction (MI) patients. The
treatment is safe and improves ejection fraction (EF).
Inventors: |
de la Fuente; Luis M.;
(Buenos Aires, AR) ; Stertzer; Simon H.; (Santa
Fe, NM) ; Argentieri; Julio; (Buenos Aires, AR)
; Penaloza; Eduardo; (Buenos Aires, AR) ; Altman;
Peter A.; (Menlo Park, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
BioCardia, Inc. |
San Carlos |
CA |
US |
|
|
Family ID: |
40721901 |
Appl. No.: |
15/341471 |
Filed: |
November 2, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14630305 |
Feb 24, 2015 |
9517199 |
|
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15341471 |
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|
13953961 |
Jul 30, 2013 |
9504642 |
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14630305 |
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11735869 |
Apr 16, 2007 |
8496926 |
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13953961 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 35/28 20130101;
A61K 9/0019 20130101; A61K 35/35 20130101; A61K 35/14 20130101;
A61P 9/00 20180101; A61K 35/32 20130101 |
International
Class: |
A61K 9/00 20060101
A61K009/00; A61K 35/14 20060101 A61K035/14; A61K 35/32 20060101
A61K035/32; A61K 35/28 20060101 A61K035/28; A61K 35/35 20060101
A61K035/35 |
Claims
1. (canceled)
2. A method of treating myocardial infarction comprising:
identifying a patient with myocardial infarction with areas of
myocardial infarct within the patient's myocardium; and
transendocardially injecting a therapeutic preparation comprising
30,000,000 to 264,000,000 concentrated mononuclear cells into
myocardium of the patient near or in an area of infarcted tissue
resulting from myocardial infarct, where said mononuclear cells
were harvested from autologous bone marrow cells from the
patient.
3. The method of claim 2, wherein said at least 40% of said
concentrated mononuclear cells are (a) CD-34 positive cells, (b)
CD-90 positive cells, (c) CD-133 positive cells, or (d) a
combination of CD-34 positive cells, CD-90 positive cells, and/or
CD-133 positive cells.
4. The method of claim 2, wherein said concentrated mononuclear
cells comprises at least 40% CD-34 positive cells.
5. The method of claim 2, wherein said concentrated mononuclear
cells comprises at least 40% CD-133 positive cells.
6. A method of treating myocardial infarction comprising:
identifying a patient with myocardial infarction with areas of
myocardial infarct within the patient's myocardium;
transendocardially injecting a therapeutic preparation into the
myocardium of the patient near or in areas of myocardial infarct,
where said therapeutic preparation comprises concentrated CD-34
positive cells and CD-133 positive cells harvested from autologous
bone marrow cells of the patient and suspended in solution.
7. The method of claim 6, wherein said at least 40% of said
concentrated mononuclear cells are (a) CD-34 positive cells, (b)
CD-90 positive cells, (c) CD-133 positive cells, or (d) a
combination of CD-34 positive cells, CD-90 positive cells, and/or
CD-133 positive cells.
8. The method of claim 6 wherein said therapeutic preparation
comprising at least 40% CD-34 positive cells.
9. The method of claim 6 wherein said therapeutic preparation of
the cells comprising at least 40% CD-133 positive cells.
10. The method of claim 6 wherein a concentration of mononuclear
cells including CD-34 positive cells, CD-133 positive cells or a
combination thereof is in the range from 10.sup.8 concentrated
cells/ml of solution to 1.2.times.10.sup.8 concentrated cells/ml of
solution.
11. A method of treating myocardial infarction comprising:
identifying a patient with myocardial infarction having an ejection
fraction less than 40%; and transendocardially injecting a
therapeutic preparation comprising concentrated CD-34 positive and
CD-133 positive mononuclear cells into myocardium of the patient,
where said mononuclear cells were harvested from autologous bone
marrow cells from the patient.
12. The method of claim 11 wherein the therapeutic preparation
comprises 30,000,000 to 264,000,000 concentrated mononuclear cells
comprising CD-34 positive and CD-133 positive mononuclear
cells.
13. The method of claim 11, wherein said at least 40% of said
concentrated mononuclear cells are (a) CD-34 positive cells, (b)
CD-90 positive cells, (c) CD-133 positive cells, or (d) a
combination of CD-34 positive cells, CD-90 positive cells, and/or
CD-133 positive cells.
14. The method of claim 11 wherein said therapeutic preparation
comprises at least 40% CD-34 positive cells.
15. The method of claim 11 wherein said therapeutic preparation
comprises at least 40% CD-133 positive cells.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 14/630,305, (Attorney Docket No.
29181-708.302), filed Feb. 24, 2015, now U.S. Pat. No. ______,
which is a continuation of U.S. patent application Ser. No.
13/953,961, (Attorney Docket No. 29181-708.301), filed Jul. 30,
2013, now U.S. Pat. No. ______, which is a continuation of U.S.
patent application Ser. No. 11/735,869, (Attorney Docket No.
29181-708.201), filed Apr. 16, 2007, now U.S. Pat. No. 8,496,926,
the entire contents of which are incorporated herein by reference
in their entirety.
BACKGROUND OF THE INVENTION
1. Field of the Invention
[0002] The inventions described below relate the field of
cardiology.
[0003] Chronic Myocardial Infarction refers to myocardial tissue
which has died as the result of myocardial infarct, and has over
the course of time become remodeled to scar tissue within the
myocardium. Left untreated, myocardial infarction induces global
changes in the ventricular architecture in a process called
ventricular remodeling. Eventually, the patient experiences
ventricular dilation and ventricular dysfunction. This ventricular
remodeling is a major cause of heart failure.
[0004] While there are several suggested means of ameliorating the
effects of acute myocardial infarction (immediately after the event
leading to infarct), no significant therapy has been proposed or
implemented for the amelioration or reversal of chronic myocardial
infarction and the deleterious effects of infracted tissue after
substantial transformation or remodeling of the infracted tissue to
scar tissue.
SUMMARY OF THE INVENTION
[0005] The method of treating chronic myocardial infarction
described below comprises injection of autologous bone marrow
derived mononuclear cells, or cells derived from those mononuclear
cells, into the myocardium. These cells are injected near or in the
chronic infracted tissue.
BRIEF DESCRIPTION OF THE DRAWINGS
[0006] FIG. 1 is a graph showing improvement in ejection fraction
of the patients in an experimental group, after injection of
autologous bone marrow derived mononuclear cells.
[0007] FIG. 2 is a graph showing improvement in exercise tolerance
of the patients in an experimental group, after injection of
autologous bone marrow derived mononuclear cells.
[0008] FIG. 3 is a graph showing improvement in ventricular
diastolic volume of the patients in an experimental group, after
injection of autologous bone marrow derived mononuclear cells.
DETAILED DESCRIPTION OF THE INVENTION
[0009] Chronic myocardial infarction refers to the condition of
infracted tissues after the infracted tissue has been remodeled by
natural wound healing responses and comprises, after such
remodeling, scar tissue, which is substantially dead. This is
distinct from ischemic tissue characteristic of chronic ischemia,
which refers to tissue which is chronically hypoxic due to lack of
sufficient blood flow, but is still viable even if not fully active
in the muscular and electro-physiologically activity of the heart.
The method starts with identifying patients afflicted with chronic
myocardial infarction. Once patients with chronic myocardial
infarction are identified, their suitability for treatment under
the method currently requires a low ejection fraction (less that
about 40%). In our experiments aimed at determining if the
treatment is safe, we included patients with left ventricular
dysfunction (less that about 40% but not less than about 30%) that
were not candidates for ventricular aneurysm surgery, implantable
defibrillators, or valve repair or replacement, while excluding
patients with active infections, malignancies, high grade
atrioventricular block, sustained ventricular tachyarrythmias, a
recent MI (less than 4 weeks old), presence of an artificial aortic
valve, recent history of alcohol or drug abuse or evidence of other
multi-system disease. However, given the results of our
experiments, we expect that the treatment could benefit all
patients suffering from chronic myocardial infarction so long as
they can tolerate the procedure.
[0010] Immediately prior to the catheterization necessary to
deliver the autologous bone marrow cells, the cells are collected
from suitable sites within the patient, such as the posterior iliac
crest, vertebral body and/or sternum. Bone marrow mononuclear cells
are isolated by suitable methods such as density gradient on
Ficoll-Paque Plus tubes (GE Healthcare, UK) through 100 .mu.m nylon
mesh to remove cell aggregates, and re-suspended in Ringers
solution at a concentration of 1.times.10.sup.8 cells/ml in a total
volume of 1.3 ml. These cells are prepared for injection back into
the patient within about 4 to 6 hours after harvesting. The bone
marrow derived mononuclear cells include CD-34 positive cells,
CD-133 positive cells, and CD-90 positive cells (mesenchymal stem
cells) which may also be separately isolated for injection to treat
chronic myocardial infarction. Preferably at least 40% of the cells
isolated comprise CD-34 positive cells, CD-90 positive cells, and
CD-133 positive cells or a combination thereof.
[0011] Just prior to cell delivery, the doctors performing the cell
delivery use various techniques, including ECG's, echocardiography,
and baseline orthogonal ventriculography data to define the target
infarct tissue zones. Access to the target infarct zone is
preferably via catheter, transendocardially (with the catheter tip
in the endocardial space) into the myocardium. Intramyocardial
delivery may also be accomplished through a trans-coronary venous
approach as described in BioCardia's U.S. Pat. No. 6,585,716,
through a trans-coronary arterial approach, or a trans-epicardial
approach. Any suitable catheter system can be used, though the
BioCardia.TM. helical infusion catheter and steerable guide
catheter are particularly well suited to the method. Dosage may
range from three injections of 0.1 to 0.2 ml of cell solution at a
concentration of 10.sup.8 (one hundred million) cells/ml (totaling
about 5.times.10.sup.7 cells) to 11 injections of 0.1 to 0.2 ml of
cell solution at a concentration of 1.2.times.10.sup.8 cells/ml for
a total of 1.2.times.10.sup.8 cells spread over numerous injection
cites proximate the target infarct tissue. The solution containing
the cells is injected near or at the site of an infarct, in several
small injections proximate the target infarct. Each injection is
performed slowly, and the helical injection catheter is left in the
injection site to dwell for a substantial period (about 15 to 30
seconds) to prevent back-leakage of the solution into the
endocardial space of the ventricle.
[0012] The efficacy of the treatment is reflected in FIGS. 1
through 3, which show that chronic myocardial infarct patients
treated with autologous bone marrow derived mononuclear cells
benefit from improved ejection fraction, improved exercise
tolerance, and reduced ventricular dilation. As shown in FIG. 1,
ejection fraction of the patients, as measured by 2D
echocardiography, demonstrates a statistically significant increase
at 1 week (P=0.02), 12 weeks (P=0.01), 6 months (P=0.001), and 12
months (P=0.0001) as compared to baseline. All patients in the
experimental group showed an increase in this parameter over
baseline at 6 months and 12 months. Smaller long term improvements
in diastolic volume and exercise tolerances were noted in our
experimental group, as shown in FIGS. 2 and 3. Given the results of
our experiment with a small number of patients, the method results
in significantly improved ejections fraction, reduced ventricular
dilation, and improved exercise tolerance. No increase in
ventricular arrhythmias was detected in any patient in the
experimental group.
[0013] Peripheral blood derived mononuclear cells (PBMC) and
adipose tissue derived mononuclear cells can be also be used in the
treatment, as can cells derived from those mononuclear cells
harvested from the peripheral blood or adipose tissue. While the
preferred embodiments of the devices and methods have been
described in reference to the environment in which they were
developed, they are merely illustrative of the principles of the
inventions. Other embodiments of the method, including sources of
cells and methods of isolation, and particular constituent cells of
the injected cell population may be devised without departing from
the spirit of the inventions and the scope of the appended
claims.
* * * * *