Clinical Trials Pursue Regeneration of Damaged Heart Muscle

Clinical Trials Pursue Regeneration of Damaged Heart Muscle

by David W. Sharp

WHAT'S HOT IN MEDICINE
Rank	Paper	Citations This Period (Sep-Oct 04)	Rank Last Period (Jul-Aug 04)
1	T.G. Ksiazek, et al., "A novel coronavirus associated with severe acute respiratory syndrome," New Engl. J. Med., 348(20): 1953-66, 15 May 2003. [7 institutions worldwide] *677TJ	51	3
2	C. Drosten, et al., "Identification of a novel coronavirus in patients with severe acute respiratory syndrome," New Engl. J. Med., 348(20): 1967-76, 15 May 2003. [5 European institutions] *677TJ	48	6
3	C.D. Furberg, et al. (ALLHAT officers and coordinators), "Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)," JAMA-J. Amer. Med. Assoc., 288(23): 2981-97, 18 December 2002. [Corresponding authors: Case Western Reserve U., Cleveland, OH; U. Texas Houston Health Center] *626CG	46	5
4	M.J. van de Vijver, et al., "A gene-expression signature as a predictor of survival in breast cancer," New Engl. J. Med., 347(25): 1999-2009, 19 December 2002. [Netherlands Cancer Inst., Amsterdam; Ctr. Biomed. Genetics, Amsterdam; Rosetta Inpharmatics, Kirkland, WA] *626LT	40	†
5	N. Lee, et al., "A major outbreak of severe acute respiratory syndrome in Hong Kong," New Engl. J. Med., 348(20): 1986-94, 15 May 2003. [Chinese U. Hong Kong, China] *677TJ Read about the special topic: Coronavirus	34	†
6	T.J. Lynch, et al., "Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib," New Engl. J. Med., 350(21): 2129-39, 20 May 2004. [Harvard Med. Sch., Boston, MA; Harvard Sch. Public Health, Boston, MA] *821XM	34	†
7	J.W. Moses, "Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery," New Engl. J. Med., 349(14): 1315-23, 2 October 2003. [10 U.S. institutions] *727EM	33	†
8	P.A. Rota, et al., "Characterization of a novel coronavirus associated with severe acute respiratory syndrome," Science, 300[5624]: 1394-9, 30 May 2003. [CDC, Atlanta, GA: U. Calif., San Francisco; Erasmus U., Rotterdam, Netherlands; Bernhard Nocht Inst. Tropical Med., Berlin, Germany] *683ZW	32	2
9	J.S.M. Peiris, et al., "Coronavirus as a possible cause of severe acute respiratory syndrome," Lancet, 361(9366): 1319-25, 19 April 2003. [6 Hong Kong institutions] *669HP	31	7
10	M. Fukuoka, et al., "Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer," J. Clin. Oncol., 21(12): 2237-46, 15 June 2003. [16 institutions worldwide] *690TG	30	†
SOURCE: ISI’s Hot Papers Database. the Legend.

ith reports on severe acute respiratory syndrome and other old favorites still prominent, the selected papers this time are once again outside the Top Ten. Cardiologists already have several tools to help patients who have had a heart attack (acute myocardial infarction, or AMI) but, with the longer term in view, repair of the damage remains an objective of research. Four years ago, laboratory experimental work suggested that progenitor cells derived from blood or bone marrow might help with the regeneration of damaged cardiac muscle and the coronary circulation. Two papers from Germany, published in Circulation in 2002, reported preliminary clinical studies of the infusion, into the affected coronary artery of patients who had had an AMI, of progenitor cells derived from the patient’s own bone marrow or blood.

The first study, from Dusseldorf, reached #21 in the previous Hot Papers file and now rises to #16 (B. E. Strauer, et al., Circulation, 106[15]: 1913-8, 8 October 2002; with 28 citations this period and 186 overall). At #19 is a paper from Frankfurt (B. Assmus, et al., Circulation, 106[24]: 3009-17, 10 December 2002; 27 citations this period, 154 overall). These small trials, with non-randomized controls, were designed to see if the technique is feasible in man and to gain some impression of both safety and efficacy.

Strauer et al. used bone-marrow cells only and in the 10 patients so treated found significant improvement in the damaged area—for example, at three months’ follow-up the infarcted region had more than halved. Assmus and colleagues made use of progenitor cells derived both from bone marrow (9 patients) and blood (10 patients), and, like Strauer’s group, made various measurements of cardiac performance to assess improvement. For instance, mean left-ventricular ejection fraction rose from 51.6% to 60.1% in the cell-treated patients.

Science Watch got in touch with both Prof. Bodo-Eckehard Strauer and Prof. Andreas M. Zeiher (from the Frankfurt team). Strauer reminds us of the first clinical application of this technique, in a 46-year-old man, described in 2001 (B.E. Strauer, et al., Deutsche Med. Wochenschr., 126[34-35]: 932-38, 2001). There has been "worldwide and increased interest" in this innovative procedure, he tells Science Watch, and the U.S. National Library of Medicine database confirms this claim. "There is stem-cell-induced improvement in both ventricular function and perfusion after AMI by 20-40%," he added, and recent evidence suggests benefit in chronic infarction also.

Zeiher (whose group has now reported the final one-year results from the study published as #19; see V. Schachinger, et al., J. Am. Coll. Cardiol., 44[8]: 1690-99, 2004) alludes to three developments in particular. First is the 200-patient European double-blind placebo-controlled randomized trial known as REPAIR-AMI, for which recruitment is already beyond the halfway stage. Also, and spreading the indications beyond simple AMI, there is a 100-patient study in patients with chronic heart failure due to coronary artery disease and the Frankfurt group’s own pilot study in 30 patients with idiopathic dilated cardiomyopathy. All three trials are making use of bone-marrow-derived cells, though paper #19 had not suggested much difference between the two cell sources.

In attempting to update readers on clinical research with the anti-lung-cancer agent gefitinib (Iressa), the January/February 2005 issue of Science Watch drew attention to research indicating how patients might be selected on the grounds of likely sensitivity to this new agent. Those papers were not in the Top Ten at the time; one is now (# 6) while the other is at #15 (J.G. Paez JG, et al., Science, 304[5676]: 1497-1500, 4 June 2004; 34 cites).

Mr. David W. Sharp, M.A. (Cambridge),
is a contributing editor to The Lancet, London, U.K.


	View the top 10 scientists and/or top 3 Hot Papers in Clinical Medicine; for the period of January 1, 1994-October 31, 2004.

Science Watch^®, March/April 2005, 2005, Vol. 16, No. 2
Citing URL: http://www.sciencewatch.com/march-april2005/sw_march-april2005_page5.htm