Why do we still not have a cure for PH? And other research questions

02.02.2015

In this issue of Research Corner, I will provide some insight into the challenges facing PH research, as well as answers to other research questions.

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Why do we still not have a cure for PH? In order to be able to look at curing a disease, scientists have to know why/how the disease occurs and how it progresses, which requires understanding which systems, organs and cells are involved in the generation of the disease. This knowledge allows the discovery of ways to stop and ultimately reverse that progression of the disease. In PH, there are some challenges we face with understanding how/why PH develops, that limits our ability to develop a successful cure. The first challenge is the origin of PH: PH is classified into five groups and each has its own subgroups. On the clinical level, patients can appear similar, displaying increased pulmonary artery pressure, increased pulmonary vascular resistance and right ventricle thickening. However, each subgroup of PH patients is unique at the cellular and molecular level, due to different causes of the disease. For example, group II PH is due to left heart disease, while group IV is due to blood clots in the lungs; both result in PH, but need to be treated differently. This uniqueness dictates which therapies will work while others will not, making it difficult to find a common cure that works for all these conditions. 

The second issue is progression of PH: PH in the early stages is almost asymptomatic, and many PH patients present to the clinic at the later stages of disease. At these stages, the lung blood vessels display a more complex pathology, including the blockage or closing of blood vessels and complex lesions, as opposed to the earlier stages where the blood vessels are only narrow. This makes it more challenging to reverse the condition.

The third issue is the “multifactorial” nature of PH: Several cell types are involved in PH disease pathology, which can differ depending on the origin of the disease. Endothelial, smooth muscle, and immune cells can all contribute to PH pathology and progression. This is one of the major complications for finding a cure, since some drugs can only work on one cell type but have opposite effects on another, which means that they fail in producing a significant improvement in patients. 

On the horizon: Looking at the above, you might get a bleak image of PH research, but you should not. The field of PH therapeutics is evolving very rapidly and current approved therapies have significantly improved patient life and slowed down disease progression. Scientists are, and will always be, working hard to discover new pathways involved in PH pathology, and develop novel therapeutics to find a cure for this devastating condition.

Why do some PH patients have a drop in their peak VO2, while others do not? Peak VO2 is a measure of the maximum rate of oxygen consumption. Variability in peak VO2 occurs because VO2 doesn’t only depend on PH progression: it’s also affected by underlying other cardio or pulmonary diseases; depression or anxiety. This explains the variability. 

What is the difference between a CCBs (Calcium Channel Blockers) true responder and a non-responder?  Calcium channels are the major channels regulating calcium uptake into the cell. Calcium is important in PH because it can control the contraction of smooth muscle cells, thus blocking calcium intake, using CCBs, can result in more relaxed blood vessels in the lungs. To determine if CCBs can be used, an initial acute vaso-reactivity test using a vasodilator factors (such as nitric oxide inhalation) has to be performed. If the pulmonary pressure decreases with this acute exposure, then the patient can be treated with CCBs.  

Please always keep in mind that while I can provide you with a small insight into PH research, you should always be able to get answers from your Pulmonary Hypertension Specialist, who is more familiar with your specific case and your treatment history.

Contributed by: Mohamad Taha, Ph.D. candidate and pulmonary hypertension researcher in Dr. Duncan Stewart's laboratory at the University of Ottawa

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