Human beings are the most evolved organisms on the planet. Many of their tissues can continuously renew throughout life, like blood cells, lining of the gut, etc. On the other hand, organs like the heart cannot regenerate. Therefore, any damage caused by a heart condition is permanent and results in the weakening of the heart, known as heart failure (1).
Since a long time, Dr. Lawrence Lum, an Associate Professor of Cell Biology has been working on developing a cancer drug that targets the Wnt signaling molecules. These Wnt signaling molecules play an important role in tissue regeneration and frequently contribute to cancer (2). An enzyme known as porcupine (Porcn) is needed for the production of Wnt proteins in humans. The enzyme is named so because in absence of this gene the fruit fly embryo looks like a porcupine (1). Small molecules that disable the Wnt acyltransferase Porcn are candidate anticancer agents in clinical testing. For the study, researchers systematically assessed the effects of the Porcn inhibitor (WNT-974) on regeneration of different types of tissues so that they could recognize the undesired chemical effects that could restrain the therapeutic utility of such agents (1). During this process the researchers came across an unanticipated observation in the cardiac tissue, which showed that the number of dividing cardiomyocytes (heart muscle cells) had slightly increased (1). Thus, it was seen that porcupine inhibitors may be used as anticancer agents, but can also be of great use in regenerative medicine.
On the basis of these findings, a study was done on mice models. During this study, researchers induced heart attacks in mice and then treated them with a porcupine inhibitor. The study concluded that the heart’s ability to pump blood improved by nearly twofold in those treated with porcupine inhibitor as compared to untreated animals. (1)
The findings of this study were published online in Proceedings of the National Academy of Sciences.
According to Dr. Rhonda Bassel-Duby, who is the Professor of Molecular Biology and has been studying heart repair since a long time, improvement of heart function after a heart attack in mice by administering Wnt inhibitor is great news. Furthermore, it was seen that not only the heart’s pumping ability improved but also there was reduction in fibrosis in the hearts (1).
According to Dr. Lum, who is a Scholar in Medical Research, the fibrotic responses can be helpful in the short term but they overcome the heart’s ability to regenerate in the long run. This study reveals an agent that can hamper the fibrotic response, thereby improving healing process of the heart. Furthermore, the other benefit that was seen during these preliminary experiments was that the porcupine inhibitor has to be used for a short duration following a heart attack, thus the unpleasant side effects commonly caused by anti-cancer drugs could be avoided (1).
Credit: Dr. Rachita on behalf of Borderless Access
Copyright © 2016 BorderlessAccess
- UT Southwestern Medical Center. “Cancer drug could promote regeneration of heart tissue.”
- Jesung Moon, Huanyu Zhou, Li-shu Zhang, Wei Tan, et al. Blockade to pathological remodeling of infarcted heart tissue using a porcupine antagonist. Proceedings of the National Academy of Sciences, 2017
Wanadamu ndio viumbe walioendelea zaidi duniani. Nyingi za tishu zao zinaweza kurejeshwa daima katika maisha yao yote, kama vile chembe za damu, utando wa matumbo, na kadhalika. Kwa upande mwingine, viungo kama vile moyo haviwezi kujirekebisha. Kwa hiyo, uharibifu wowote unaosababishwa na ugonjwa wa moyo ni wa kudumu na husababisha udhaifu wa moyo, unaojulikana kama kushindwa kwa moyo (1). Kwa miaka mingi, Lawrence Lum, profesa wa biolojia ya seli, amekuwa akifanya kazi ya kuendeleza dawa ya kansa ambayo inalenga molekuli za ishara za WNT. Wnt signaling molecules huchangia sana katika regeneration ya tishu na mara nyingi huchangia kansa. Enzyme inayojulikana kama porcupine (Porcn) inahitajika kwa ajili ya uzalishaji wa protini za Wnt katika wanadamu. Enzyme hiyo inaitwa hivyo kwa sababu ikiwa haina jeni hilo, kiinitete cha nzi wa matunda huonekana kama porcupine (1). Molekuli ndogo ambazo huficha Wnt acyltransferase Porcn ni wagombea wa dawa za kansa katika majaribio ya kliniki. Kwa ajili ya utafiti huu, watafiti walipima madhara ya Porcelain inhibitor (WNT-974) juu ya kuzaliana kwa aina tofauti za tishu ili waweze kutambua athari zisizohitajika za kemikali ambazo zinaweza kuzuia matumizi ya matibabu ya dawa hizo. Katika uchunguzi huo, watafiti walipata kwamba idadi ya chembe za moyo (cardiomyocytes) zilizokuwa zikigawanyika ilikuwa imeongezeka kidogo. Kwa hivyo, ilionekana kwamba kizuizi cha porcupine kinaweza kutumika kama mawakala wa kupambana na saratani, lakini pia kinaweza kutumika sana katika dawa ya kurudisha. Kwa msingi wa matokeo haya, utafiti ulifanywa kwenye mifano ya panya. Katika utafiti huo, watafiti walifanya panya wapate mshtuko wa moyo na kisha wakawatibu kwa dawa ya kuzuia ugonjwa wa porcupine. Utafiti huo ulionyesha kuwa uwezo wa moyo wa kupumua damu uliboreshwa karibu mara mbili kwa wale waliotibiwa na kuzuia porcupine ikilinganishwa na wanyama ambao hawakutiwa dawa. Matokeo ya utafiti huo yamechapishwa kwenye jarida la Proceedings of the National Academy of Sciences. Rhonda Bassel-Duby, profesa wa biolojia ya molekuli, anasema kuwa kuimarika kwa moyo baada ya mshtuko wa moyo ni jambo la kushangaza. Kwa kuongezea, ilionekana kwamba sio tu uwezo wa pampu ya moyo uliboreshwa lakini pia kulikuwa na kupunguzwa kwa fibrosis katika mioyo (1). Kulingana na Daktari Lum, ambaye ni msomi katika utafiti wa matibabu, majibu ya fibrotic yanaweza kuwa na msaada kwa muda mfupi lakini hushinda uwezo wa moyo wa kuzalisha tena kwa muda mrefu. Utafiti huu unafunua kiungo kinachoweza kuzuia majibu ya fibrotic, na hivyo kuboresha mchakato wa uponyaji wa moyo. Kwa kuongezea, faida nyingine iliyoonekana wakati wa majaribio haya ya awali ni kwamba kizuizi cha porcupine kinapaswa kutumiwa kwa muda mfupi baada ya mshtuko wa moyo, hivyo athari mbaya za upande zinazosababishwa na dawa za kupambana na kansa zinaweza kuepukwa. "Mwanamke huyo, Dr. Rachida, ambaye ni msaidizi wa shirika la ""Borderless Access"" (BWA), amesema kuwa ""hatua hii ni ya kwanza katika historia ya matibabu ya binadamu." "Dawa ya kansa inaweza kukuza kuzaliwa upya kwa tishu ya moyo". - Jesung Moon, Huanyu Zhou, Li-shu Zhang, Wei Tan, et al. Kuzuia kurekebisha ugonjwa wa tishu ya moyo infarcted kwa kutumia pig-spine antagonist. Machapisho ya Chuo cha Kitaifa cha Sayansi, 2017