Minimally invasive gene therapy delivery and method

Details Minimally invasive gene therapy delivery and method Minimally invasive gene therapy delivery and method

1999-09-10

2001-11-27

Sykes, Angela D. (Department: 3762)

Surgery

Means for introducing or removing material from body for...

Treating material introduced into or removed from body...

C604S019000, C604S116000, C604S272000, C604S181000, C604S187000, C128S898000, C600S372000, C600S374000, C606S008000

Reexamination Certificate

active

06322536

ABSTRACT:

FIELD OF THE INVENTION
This invention embodies a therapeutic medical device and a method of treatment. In particular, the device is suitable for treating target tissue of a patient by injection of predetermined quantities of a substance into bodily tissue at successive locations within the patient's body. One particular application to which this invention may be applied is the delivery of therapeutic substances to the heart to induce angiogenesis for improving blood flow in heart tissue.
BACKGROUND OF THE INVENTION
Despite the recent advances in the treatment of ischemic heart disease, there still exist a significant number of patients for whom conventional therapies such as angioplasty and coronary bypass surgery are not feasible options. In particular, alternative therapies are required for patients in a number of circumstances. For example, patients with diffuse small vessel coronary artery disease cannot be treated by conventional coronary bypass surgery because of the small size and large number of diseased vessel segments. In other patients, re-occlusion of a diseased vessel may occur despite multiple angioplastic procedures or bypass surgeries. Accordingly, the need exists for alternative intervention methods.
One promising alternative treatment for ischemic heart disease is the delivery of angiogenesis-promoting substances to the heart tissue to induce angiogenesis. Angiogenesis is a complex biological process that results in the growth of new blood vessels within tissue. Angiogenesis is an essential process common to several normal and pathologic conditions including embryologic development, wound healing, development of neoplasms, and the like.
Angiogenesis has also been induced in heart tissue for re-perfusion of tissue compromised by myocardial ischemia. Several growth factors have been identified and are intimately involved in initiating and promoting angiogenesis in tissue within a living body. These growth factors are typically proteins which stimulate endothelial cell reproduction in the target tissue. The tissue must be exposed to the growth factors for a period of time, i.e., a number of days. In addition, the growth factor should be limited to the target tissue so that angiogenesis is not induced in sensitive non-diseased organs, such as the retina, or in occult tumors.
The growth factor may be delivered to the target tissue through the use of indwelling catheters over a period of time. However, a preferred method of delivering the growth factor is in the form of gene transfer by a replication deficient adenoviral vector. Under this method, a quantity of adenovirus having the desired genetic component is delivered to the treatment area by injection in solution.
In the past, an open-chest procedure has been used to deliver the treatment solution. According to this procedure, the patient's chest is opened surgically to expose the heart. The solution containing the adenovirus is then delivered to the heart tissue by using a syringe to make a number of injections in a grid-like pattern, with the surgeon keeping track of the location of each injection. Once injected, the adenovirus causes the cells in the target tissue to express the desired growth factor protein, and this protein expression from the treated cells will continue for the desired period of time. Previous studies have shown the feasibility and efficacy of safe, sustained, and localized expression of angiogenesis-promoting growth factors utilizing adenoviral-mediated gene transfer therapy.
It is desirable, however, to be able to provide the above-described therapy without the necessity of performing open-chest surgery on the patient. Accordingly, the present invention sets forth an apparatus and method for providing gene therapy treatment to the heart or other internal organs in a minimally invasive manner. The present invention also provides an apparatus and method for delivering angiogenesis-promoting substances to an area of diseased tissue with greater ease and efficiency, and with reduced trauma and recovery time for the patient. Accordingly, the subject invention could be potentially helpful to hundreds of thousands of patients with severe ischemic heart disease who are not candidates for surgical bypass or balloon angioplasty.
SUMMARY OF THE INVENTION
The present invention embodies a novel, minimally invasive injection apparatus and method. The invention is useful, for example, in gene transfer therapy for injecting an angiogenesis-promoting factor into living tissue, such as into the myocardium. The injection device includes an elongate flexible tubular body having a proximal end and a distal end. A hollow needle is mounted on the distal end of the tubular body. The needle is capable of penetrating the target tissue for delivering a therapeutic substance to the tissue.
In addition, a marking device and a method of marking are preferably provided. The marking device may result in a physical indication that may be viewed thoracoscopically, as would be effected, for example, by including a dye or the like in the injected substance, or other physical marking the location of the injection. In the illustrated embodiment, the marking device is in the form of a marking element mounted on a platen on the distal end of the tubular member. When the therapeutic substance is delivered to the bodily tissue, the marking element leaves a discernible mark on the target tissue so that the surgeon may keep track of which areas of tissue have been treated by viewing though a thoracoscope, or by other means. Preferably, a stop is provided which is spaced in from the distal tip of the needle. The stop regulates the distance to which the needle may penetrate the target tissue. In an illustrated embodiment, the platen and needle are fixed relative to each other so that the platen, by contacting the tissue surface, acts as a stop and ensures that the needle penetrates the target tissue to the same depth with each injection.
Alternate methods of marking and marking devices may result in markers or indications that may be detected thoracoscopically, ultrasonographically, radiographically, or fluoroscopically, as, for example, by x-ray or CAT scan, or by other three-dimensional imaging systems. Virtual marking or mapping may likewise be utilized. With electrocardiographic marking, as by ECG, an electrode preferably is provided at the end of the needle, while the remainder of the device is insulated.
A control apparatus may also be included with the device for controllably positioning the distal end of the tubular member to facilitate proper positioning and insertion of the needle. Furthermore, a metering device may also be included for controlling the amount of therapeutic substance injected at each successive injection site.
Under the method of the invention, a therapeutic substance may be injected into living tissue successively at a plurality of locations inside the body in a minimally invasive manner. The injections may be made for a variety of purposes in a variety of bodily tissues. However, the present invention is especially suitable for delivering gene therapy to the heart. In particular, an angiogenesis-promoting factor may be introduced into myocardial territories in predetermined quantities at a plurality of points to induce the growth of bypass vessels which may allow the bridging of narrowed or occluded coronary vessels. The treatment may also be used to induce the growth of new vessels in myocardial territories poorly supplied by the native coronary vasculature. The treatment method may also be used to deliver therapeutic substances to other bodily tissues in a minimally invasive manner.
Under an additional method of the invention, a patient's lung may be partially collapsed by the introduction of gas into the patient's thoracic cavity. This enlarges the working area for injection of the therapeutic substance and increases access to heart tissue. The delivery of the therapeutic substance to the myocardium may be made transpericardially, rather than from within the pericardium. An elect

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