HGF-1 Double Blind Trial for Critical Limb Ischemia

Durham, NC -

Stimulation of angiogenesis has previously been demonstrated using various cell therapy methods, such as administration of autologous bone marrow stem cells either in the heart or ischemic leg muscle.  Autologous approaches sometimes are difficult since on the one hand they require cellular processing, which may not be available at most institutions, and on the other hand autologous stem cells may be aged or possess dysfunction in ability to secrete angiogenic factors.  One way of circumventing this is to use allogeneic cells that are predefined, such as the endometrial regenerative cell population or the bone marrow derived mesenchymal stem cell population. 

Another method of stimulating angiogenesis involves direct administration of angiogenic factors.  These factors may be administered as proteins, as being performed by the company CardioVascular Biotherapeutics (CVBT), which are using recombinant FGF-1, or may be plasmids encoding growth factors, such as the NV1FGF product.

In a recent study (Powell et al. Results of a Double-Blind, Placebo-Controlled Study to Assess the Safety of Intramuscular Injection of Hepatocyte Growth Factor Plasmid to Improve Limb Perfusion in Patients With Critical Limb Ischemia. Circulation. 2008 Jun 16) results of 104 patients treated with HGF encoding plasmid in a double blind trial were reported.   

Patients were randomized to recieve placebo or three various doses of HGF plasmid (0.4 mg (days 0, 14, and 28), 4.0 mg (days 0 and 28) and 4.0 mg days 0, 14, and 28)).  Patients eligible for the trial had to suffer from either rest pain or ulcers and transcutaneous oxyge of less than 40 mm Hg, and/or toe pressure of less than 50 mm Hg. 

No significant adverse events were associated with treatment, although a very high level of adverse events was seen (86%), most likely due to the poor prognosis of patients selected to enter the trial.

An increase in transcutaneous oxygen was seen in all three groups as compared with placebo at 6 months.

Unfortunately no difference was observed in: ABI, toe brachial index, VAS pain, wound healing, or amputation.

For future investigations it may be interesting to combine stem cells with such gene therapy approaches.  Particularly given that some stem cells have the ability to "follow the leader".