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Reversing Ischemia with Gene therapy

Ischemia treatment market

A human body comprises of many small, long, narrow and broad blood vessels that carry oxygenated blood from the heart to other body parts for their normal functioning. However, due to life style-shifting more towards a sedentary one, and inculcation of bad food habits, there has been an increase in the number of non-communicable diseases like cardiovascular diseases, diabetes, obesity, and ultimately leading to Ischemia.

What is Ischemia?

Ischemia is a condition that results in a blockade of the arteries of the body. It is a restriction in the supply of the blood through the blood vessels resulting in scarcity of the oxygen. In the dearth of sufficient oxygen, there are disturbances in normal cellular and circulatory processes, thus resulting in tissue dysfunction.

Types of Ischemia

Based on the arteries, Ischemia afflicts, it is categorised into five types, namely, Cardiac Ischemia, Bowel Ischemia, Brain Ischemia, Limb Ischemia, and Cutaneous Ischemia.  

Why does it happen?

Impediment in the availability of enough oxygen results in a condition known as atherosclerotic plaque. The plaque which constitutes excess fat, cholesterol, and other products gets deposited on the walls of the coronary arteries narrowing their circumference.

Whenever the demand for oxygen is more than the supply, Ischemia develops.

In layman language, Ischemia usually does not occur when the body is at leisure or rest.  However, during extreme physical work like exercising oxygen demand soars up and plagued arteries fail to deliver the same, resulting in angina pectoris. It is a condition which describes pain and discomfort in the heart muscles due to insufficient blood supply.

Occlusion

In addition to this, Ischemia can also occur if there is a formation of embolus, a condition known as Arterial embolism. An embolus is a term for foreign materials that traverse through a blood vessel and adheres to the wall of an artery, which is too small for it to pass through. This is referred to as thromboembolism when the substance stuck in the artery is a blood clot. If the clot lyses, muscles will relax, and there would be enough oxygen to fulfil the requirement preventing Ischemia.

Moreover, Ischemia may occur due to undue pressure on the blood vessels, known as Vasoconstriction.

There also exists chances that a patient may have Ischemia and may be unaware of it. This is referred to as Silent Ischemia, which has no symptoms. It is characterised by unusual pumping of the heart and abnormal heart rhythms.

Ischemia Treatment market 

Ischemia treatment varies with the location of the ischemia and its severity. However, Common factors that increase the risk of Ischemia such as tobacco, diabetes, high blood pressure, high blood cholesterol level, and minimal or nil physical activity should be taken care of and eliminated. Curbing them may help in preventing the Ischemia progression and reduces the chances of death.

The treatment goals of Ischemia focus on increasing blood flow to the arteries. This can be accomplished in several ways: Medications, Exercise, and Surgery or Endovascular Procedures.

Furthermore, medications are prescribed to stop Ischemia progression. Also, to limit the risk of Ischemia, medications are prescribed for contributing factors such as diabetes, blood pressure and others. In addition to this, medicines are present in the Ischemia treatment market to stop excess blood clotting. Ischemia patients are also advised to follow a strict and supervised exercise routine. To address the pain due to Ischemia, a condition known as claudication, medications exist.

The symptomatic approach of Ischemia treatment landscape includes cholesterol-lowering drug (statin), Cilostazol (Pletal) for reducing pain due to claudication by widening (dilating) the arteries, and aspirin-dipyridamole as an antiplatelet therapy for acute cerebral ischemia are prescribed.

In addition to the medicinal drugs, Ischemia treatment market also comprises of Revascularization (Angioplasty, or bypass surgery) for the purpose of widening of the arteries.

How Gene Therapy is fueling Ischemia treatment market

The present Ischemia treatment landscape is symptomatic and has several limitations and unmet needs. For instance, the standard treatment for Ischemic heart disease, as mentioned above, is percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Yet, the after-treatment phase of the patient’s does not go as smoothly as it seems so. Treatment approaches undertaken for Ischemia treatment are often accompanied by several complications and side effects and demands the need for repeated procedures in case of revascularisation.

However, the last decades have brought many advances in the understanding of the different forms of Ischemia, their pathophysiology, symptoms and the treatment of leading mortality causing forms Ischemia, i.e., Critical Limb Ischemia and Ischemic Heart Disease. However, the present Ischemia treatment landscape has several limitations and unmet needs.

Gene therapy offers a striking alternative approach to current supportive and pharmacological treatments for Ischemia. Many pieces of research and clinical studies have shown promising results of innovative DNA-based gene therapy. Gene therapy, the latter approach to offer a permanent therapeutic cure to any disease with unmet needs, has been successful in treating many disorders so far. Ischemia can be one of them.

Myocardial Ischemia and Critical limb ischemia (CLI) represent the most advanced stages of atherosclerotic and are often associated with high rates of morbidity and mortality.  In cases of Myocardial Ischemia death is often seen as about 150,000 individuals die of stroke every year, whereas in CLI amputations are common. Critical Limb Ischemia incidence is estimated to be ranging from 125,000 to 250,000 patients per year in the United States.

Gene therapy promises a continuous supply of proteins required for the normal functioning of the body at the site of need. Not only Gene therapy has the potential of offering one-time treatment, but it also has the potential to reverse the pathophysiology associated with Ischemia.

In a recent finding (by Sunkomat JN, Gaballa MA.), it was revealed that stem cells contribute to the formation of new blood vessels a process known as neovascularisation, can possibly revolutionise how the heart failures are treated. Stem cell-based therapies deliver cells with regenerative properties, substantiates cardiac regeneration, improves cell survival, and tissue remodelling. Stem cells therapies, when combined with gene therapy, shows a higher rate of success.    

However, there is still a long way to go. Lack of positive results due to the poor rate of survival and poor retention of transplanted cells in the injured tissues and cells along with the route of administration remain as the major areas that need attention.

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