Chronic obstructive pulmonary disease (COPD)
Background
Chronic Obstructive Pulmonary Disease (COPD) is a common and severe lung disease affecting around 400 million people in the world, corresponding to a global prevalence of 10.7 % in the age group of 30 years or more1. Patients experience impaired physical fitness, increasing breathlessness, coughing, and a number of other symptoms. The disease is usually progressive in spite of all existing treatment. COPD caused an estimated 2.75 million deaths globally2 in 2000 (fourth leading cause of death) and the morbidity rates are growing every year.
1. Davies Adeloye et al. Global and regional estimates of COPD prevalence: Systemic review and meta-analysis. J Glob Health. 2015 Dec; 5(2): 020415.
2. David M Mannino and Victor A Kiri. Changing the burden of COPD mortality. Int J Chron Obstruct Pulmon Dis. 2006 Sep; 1(3): 219–233.
Causes of COPD
COPD has traditionally been seen as mainly caused by tobacco smoke. Tobacco smoke contains many hazardous substances such as carbon monoxide, nicotine, tar, irritants and other noxious gases. There are also considerable amounts of heavy metals in the smoke such as lead, cadmium and mercury1. No one knows what component in the smoke that is the most harmful to the lungs.
Today, more and more people in the world are affected by COPD without smoking. It is now considered that air pollutants and various industrial emissions are also important risk factors for COPD2.
1. M. Chiba and R. Masironi. Toxic and trace elements in tobacco and tobacco smoke. Bull World Health Organ. 1992; 70(2): 269–275.
2. Li Li, Jun Yang, Yun-Feng Song, Ping-Yan Chen & Chun-Quan Ou. The burden of COPD mortality due to ambient air pollution in Guangzhou, China. Scientific Reports 6, Article number: 25900 (2016).
Hypothesis
PharmaLundensis project is based on the hypothesis that the tobacco smoke’s content of heavy metals such as lead, cadmium and mercury play a key role in the development of COPD1+2. A significant association between obstructive lung disease and serum cadmium and lead has previously been found3. Also, it has been found that smoking is positively associated with mercury accumulation4. When smoke is inhaled, a considerable amount of heavy metals such as mercury (Hg) will be retained in the airway epithelial cells5, because they have a high oxidative capacity. As a result, epitelial cells convert Hg0 to Hg2+ which is trapped within them. The build-up in the airways of heavy metals from the smoke impairs a crucial relaxant mechanism located in the epithelium. It has previously been shown by Dr Staffan Skogvall that a specific type of epithelial cells, so-called neuroepithelial endocrine (NEE) cells, release a powerful relaxing factor that normally keeps the airways open6. According to the hypothesis, the release of this relaxing factor decreases when heavy metals build up in the epithelial cells as a result of smoking, causing a gradual closure of mainly the small airways. This causes the airway obstruction that is typical for COPD.
1. M. Chiba and R. Masironi. Toxic and trace elements in tobacco and tobacco smoke. Bull World Health Organ. 1992; 70(2): 269–275.
2. Suzuki T, Shishido S, Urushiyama K. Mercury in cigarettes. Tohoku J Exp Med. 1976 Aug;119(4):353-6.
3. Haala K.Rokadia, ShikharAgarwal,Serum Heavy Metals and Obstructive Lung Disease: Results From the National Health and Nutrition Examination Survey. Volume 143, Issue 2, February 2013, Pages 388-397.
4. Hong D1, Cho SH, Park SJ, Kim SY, Park SB. Hair mercury level in smokers and its influence on blood pressure and lipid metabolism. Environ Toxicol Pharmacol. 2013 Jul;36(1):103-7.
5. Khayat A, Dencker L.Whole body and liver distribution of inhaled mercury vapor in the mouse: influence of ethanol and aminotriazole pretreatment. J Appl Toxicol. 1983 Apr;3(2):66-74.
6. Skogvall S, Korsgren M, Grampp W. Evidence that neuroepithelial endocrine cells control the spontaneous tone in guinea pig tracheal preparations. J Appl Physiol. 1999 Mar;86(3):789-98.
New and effective treatment of COPD with Iodocarb
PharmaLundensis COPD treatment IodoCarb is a substance which effectively binds and removes heavy metals from the body. Iodocarb consists of activated charcoal with adsorbed iodine. Activated charcoal is widely used in medicine to remove toxic substances from patients exposed to them1. It is possible to further strongly increase the heavy metal binding capacity of activated charocal by impregnating it with iodine2. Impregnation with iodine increases the metal binding capacity by more than 100 times (10 000 %)3.
1. Neuvonen PJ, Olkkola KT. Oral activated charcoal in the treatment of intoxications. Role of single and repeated doses. Med Toxicol Adverse Drug Exp. 1988 Jan-Dec;3(1):33-58.
2. Henning K-D and Schäfer S. Impregnated activated carbon for environmental protection. Gas Sep Purif 1993 Vol 7(4):235-240.
3. Yoshimi Matsumura. Adsorption of mercury vapor on the surface of activated carbons modified by oxidation or iodization. Atmospheric Environment (1967), Volume 8, Issue 12, December 1974, Pages 1321-1327.
Mechanism of action
It is considered that Iodocarb acts by binding and removing heavy metals from the body. How can oral Iodocarb, which is not absorbed in the body but merely passes through the intestine, improve the lung function? Heavy metals often display an enterohepatic circulation where they are excreted by the liver in the bile, enters the small intestine and is subsequently readsorbed into the body again further down the small intestine1+2. As a result, it is very difficult for the body to excrete heavy metals. When Iodocarb is present in the small intestine, heavy metals excreted in the bile are adsorbed to the iodinated activated charcoal and excreted in the faeces, rather than being readsorbed back into the body. This breaks the circulation, thereby allowing a greatly increased excretion of heavy metals.
1. Huang W, Zhang P, Xu H, Chang S, He Y, Wang F, Liang G. A novel route for the removal of bodily heavy metal lead (II). Nanotechnology. 2015 Sep 25;26(38):385101.
2. Factors involved in heavy metal poisoning. Fed Proc .
Iodocarb comp
In order to reduce the absorption of iodine released from Iodocarb in the intestine, an inhibitor of the sodium/idodide symporter (iodine pump) can be added to the treatment. The iodine pump inhibitor potassium perchlorate has been used for many years to treat thyreotoxicosis in humans1. The iodine pump is responsible for absorption of iodide in the intestine2, the thyroid3 and the kidneys4. The combination of Iodocarb and the iodine pump inhibitor potassium perchlorate is called Iodocarb comp. Preliminary experiments suggest a reduction of the thyroid side effects. Surprisingly, they also suggest that Iodocarb comp give a synergistic improvement of the lung function. One 80-year old caucasian male got almost the double improvement of the lung function by Iodocarb comp, compared to only Iodocarb. This synergistic improvement may be caused by potassium perchlorate reducing the release of iodine from the activated carbon as a result of the inhibition of the intestinal iodine pump, thereby allowing Iodocarb to bind heavy metals for a longer time.
1. Morgans, ME and Trotter, WR. Treatment of thyreotoxicosis with potassium perchlorate. Lancet. 1954 Apr 10;266(6815):749-51.
2. Nicola JP, Basquin C, Portulano C, Reyna-Neyra A, Paroder M, Carrasco N. The Na+/I- symporter mediates active iodide uptake in the intestine. Am J Physiol Cell Physiol. 2009 Apr;296(4):C654-62. doi: 10.1152/ajpcell.00509.2008.
3. Wolff J. Perchlorate and the thyroid gland. Pharmacol Rev. 1998 Mar;50(1):89-105.
4. Spitzweg C1, Dutton CM, Castro MR, Bergert ER, Goellner JR, Heufelder AE, Morris JC. Expression of the sodium iodide symporter in human kidney. Kidney Int. 2001 Mar;59(3):1013-23.
Iodocarb Novum
The method to produce Iodocarb is at present being modified, in order to reduce the leakage of iodine from the activated carbon. A high-quality Iodocarb which releases considerably less iodine will allow the administration of much larger amounts of Iodocarb to COPD patients. Since the Iodocarb airway relaxation most likely is dose-dependent, an increased dose will result in an even larger improvement of the lung function than what was found in the previous clinical stydy (130 ml improvement of FEV1 baseline compared to placebo1).
1. Skogvall S, Erjefält JS, Olin AI, Ankerst J, Bjermer L. Oral iodinated activated charcoal improves lung function in patients with COPD. Respir Med. 2014 Jun;108(6):905-9
Use of Iodocarb comp and Iodocarb novum depends on the severity of the COPD disease
When treating patients with light – moderate COPD, it will probably be sufficient to administer Iodocarb novum as a single treatment to achieve an improved lung function. However, when treating patients with severe COPD it may be appropriate to add an iodine pump inhibitor such as potassium perchlorate to get the added benefit of the synergistic improvement of the lung function.
Future clinical studies
PharmaLundensis will initially focus on developing a treatment for chronic bronchitis, because it will be faster, easier and less expensive. Thereafter, we will also register our treatment on the indication COPD. Chronic bronchitis and COPD are closely related diseases which have the same causes (tobacco smoke and airway pollution) and often exist in the same patient.
PharmaLundensis plan to perform two clinical studies on patients with chronic bronchitis during the next few years:
1. Phase 1/2a study (60 patients).
2. Phase 2 study (140 patients).
Thereafter, a Phase 3 study with 200-500 patients is planned to allow registration of the treatment. At this point, clinical studies on COPD patients will also commence.
Treatment of air pollution-induced COPD
As mentioned above, an increasing number of patients today get COPD as a result of air pollution, rather than smoking. Air pollution, especially from the burning of fossil fuel, contain considerable amounts of heavy metals, just like tobacco smoke1+2. Since the toxic factors that cause COPD may be heavy metals in both cases, Iodocarb can also be expected to be able to treat air pollution-induced COPD. Interestingly, it may be possible to PREVENT the development of COPD if exposed to tobacco smoke or air pollution by taking a small amount of Iodocarb to remove the heavy metals from the airways. Thus, if you live in a city with heavy pollution, it may be possible to protect your lungs by regularly taking a low dose of Iodocarb, rather than leaving the polluted city.
1. Honda A, Tsuji K, Matsuda Y, Hayashi T, Fukushima W, Sawahara T, Kudo H, Murayama R, Takano H. Effects of air pollution-related heavy metals on the viability and inflammatory responses of human airway epithelial cells. Int J Toxicol. 2015 Mar-Apr;34(2):195-203.
2. https://www.epa.gov/international-cooperation/mercury-emissions-global-context#types
Patent protection
The main patent for Iodocarb (WO2009067067) is valid in most countries in the EU, China, Japan and Russia. Patent protection lasts at least until 2028 and is likely to be extended for another 5 years.
National patents for Iodocarb comp (WO2015075111) has been granted in USA, Europe, Japan, Israel, Saudi Arabia and South Africa, and is pending in some more countries. Patent protection lasts until 2033 and may be extended for another 5 years.
Patents for Iodocarb novum will cover many more markets.
Business Plan
PharmaLundensis will retain marketing rights in core markets (Nordic countries and some countries in continental Europe). Pharma companies outside core markets can obtain exclusive license in their main market for the sale of Iodocarb. Please see “Licensing“.
Potential for large revenues from Iodocarb
There is a high and growing prevalence of COPD, both globally and regionally. The costs of treating COPD are massive. In the United States, the costs were $ 32.1 billion 2010, which is expected to increase to $ 49 billion by 20201. In other parts of the world, costs are also very high. In 2012, the 10 largest drugs against lung diseases generated a total of $ 25 billion in sales2. After successful registration, Iodocarb may be an international blockbuster with annual sales exceeding 1 billion dollar globally.
1. http://www.cdc.gov/features/ds-copd-costs/
2. http://www.firstwordpharma.com/node/1145830#axzz3lTHHd2ng
