GARM · Roatán, Honduras
VEGF Gene Therapy · Peripheral Artery Disease
Grow new capillaries.
Keep walking.
Without pain.
A single course of injections prompts your own body to build new blood vessels around the blockage — restoring circulation to oxygen-starved legs, with effects that last 5+ years.
Figures shown are group averages from published PAD studies; individual results vary. Experimental and not approved by the FDA. Unlimited Bio is not a medical provider; treatment is administered by independent clinics.
Real patient · Critical Limb Ischemia
Whole-leg revascularization, imaged before & after
A patient with critical limb ischemia received 4 vials of VEGF across two sessions, two weeks apart — 20+ injections distributed from hip to feet. These angiograms show the vascular network before treatment and after revascularization.
Before
After
Single real patient case. Individual results vary; angiographic response is not guaranteed.
The problem
When leg arteries narrow, tissue starves
In Peripheral Artery Disease, atherosclerotic plaque narrows the arteries feeding your legs. Blood flow drops, and muscle, skin and nerves no longer get the oxygen and nutrients they need.
Early on, that means pain when walking (claudication). As it progresses to critical limb ischemia, it brings rest pain, non-healing wounds, and a real risk of amputation. Restoring blood flow is the whole game.
Not sure if your leg pain is claudication? Take the 1-minute PAD self-test.
- Pain or cramping in the legs when walking
- Slow-healing wounds and ulcers on the legs or feet
- Cold, pale, or weakened lower limbs
- In severe cases (CLI): rest pain and amputation risk
How it works
VEGF is the master regulator of angiogenesis
Neovasculgen® delivers the VEGF gene to the target tissue via a plasmid. The cell starts producing VEGF protein locally, which signals the growth of new, functional blood vessels — natural detours around the blocked artery.
The therapy is local and tissue-targeted. The plasmid supplements the cell's activity without changing or integrating into its DNA, persists only temporarily, and cannot be passed to future generations.
01 Injection
02 Supercoiled VEGF plasmids (Neovasculgen)
03 Plasmid enters the cell
04 Plasmid enters the nucleus
06 New capillaries form
05 VEGF Protein secreted
Injection for angiogenesis
One or two courses of injections, a whole new blood supply
VEGF is delivered as a set of intramuscular injections across the oxygen-starved legs. Over the following weeks it drives local angiogenesis: your body grows a fresh network of blood vessels around the injection sites that re-perfuses the tissue.
- Inject VEGF into the ischemic leg muscles
- Blood vessels grow locally and re-perfuse the tissue
Clinical evidence
Patients walked dramatically further, and kept walking
In trials of Neovasculgen®, pain-free walking distance (PWD) climbed steeply after treatment and held for years. Even patients with the most severe circulation loss benefited most.
≈ 3.6×
VEGF plasmid + standard therapy (n=36)
Pain-free walking distance: 106 m → 384 m at 5 years (Deev, 2018).
≈ 0.9×
Standard therapy alone (n=12)
Pain-free walking distance: 99 m → 87 m at 5 years (Deev, 2018).
Show these figures as a table
| Group | Before treatment | 6 months | 1 year | 3 years | 5 years |
|---|---|---|---|---|---|
| VEGF plasmid + standard therapy (n=36) | 106 | 223 | 306 | 411 | 384 |
| Standard therapy alone (n=12) | 99 | 98 | 109 | 110 | 87 |
Show these figures as a table
| Group | Before treatment | 6 months | 1 year | 3 years | 5 years |
|---|---|---|---|---|---|
| VEGF plasmid + standard therapy (n=36) | 100% | 211% | 289% | 389% | 363% |
| Standard therapy alone (n=12) | 100% | 98% | 110% | 111% | 87% |
What changes
Clinical benefits for PAD
+177%
Pain-free walking distance
Average across treated patients at 6 months (Deev, 2017, n=150); up to +683% in Stage III / critical limb ischemia.
95%
Amputation-free survival
In the treatment group at 5 years, against 67% on standard therapy (Deev, 2018).
5+ yrs
Sustained effect
A single injection course keeps working for at least five years.
+27%
Tissue oxygenation (TcPO₂)
Sustained increase peaking at 90.7 ± 4.9 mmHg by year 2, holding at 84.1 ± 1.8 mmHg at year 5.
+24%
Ankle-Brachial Index (ABI)
At 6 months — an objective measure of leg circulation.
20,000+
Patients treated
Over a decade of real-world clinical use for PAD.
Published imaging
Angiography Before & After 6 Months
Imaging before and 6 months after Neovasculgen® administration shows new vessel formation in the treated limb (images courtesy of ArtGen Biotech).
Safety
Among the strongest safety records in gene therapy
Over 20,000 PAD patients treated, 210 followed in post-marketing surveillance across 33 facilities with 150 of them on the therapy, and on the market since 2012. Across the five-year and ten-year follow-ups the investigators recorded no adverse events they attributed to the plasmid and no impaired vision, and no individual disease occurred significantly more often than on standard therapy.
- The plasmid stays outside your chromosomes: integration after intramuscular injection is very inefficient, far below the natural mutation rate (Ledwith, 2000; Martin, 1999)
- Local leg injection raises circulating VEGF only slightly and briefly: median plasma VEGF up about 8% at day 7, back to baseline by day 14 (Freedman, 2002, n=34)
- No statistically significant excess of cancer in long-term follow-up of local VEGF gene transfer (Deev, 2018; Chervyakov, 2023; Muona, 2012; Hedman, 2009)
- 95% amputation-free survival at 5 years, against 67% on standard therapy (Deev, 2018)
- 81% amputation-free at 10 years in a separate cohort of 36 treated patients, with no adverse events attributed to the construct (Chervyakov, 2023)
A 2018 Cochrane review of gene therapy for peripheral artery disease as a class found no convincing evidence that it improves amputation-free survival, major amputation rates or mortality (Forster, 2018). The figures above come from studies of this specific plasmid, which that review weighs alongside others.
What to expect
The treatment journey
- Video callEligibility evaluation with the medical team
- Day 0Arrival & screening
- Day 1Injections — at least 10 into the ischemic muscles
- Day 2Observation (days 0–2 can be combined into one)
- Day 14+Optional second injection round for additional efficacy
Where to get it
Clinics offering VEGF therapy
GARM · Bahamas
Dr. Douglas Tucker
VEGF vs PAD.
Frequently Asked Questions
A plasmid (Neovasculgen®) delivers the VEGF gene directly into the ischemic leg muscles. The cells begin producing VEGF protein locally, which triggers angiogenesis — the growth of new, functional blood vessels that route blood around the narrowed arteries and re-perfuse oxygen-starved tissue.
People with PAD or diminished blood supply to the legs — including those with intermittent claudication (Stage IIB) and critical limb ischemia (Stage III/CLI), and patients whose circulation is compromised by type 2 diabetes or sarcopenia. A quick way to gauge whether your leg pain fits the pattern is our 1-minute PAD self-test; eligibility is then confirmed on a screening video call.
The therapy is delivered locally as a set of intramuscular injections into the ischemic muscles — at least ten per session. Severe cases may receive more injections distributed across the whole limb, and an optional second round 2 weeks later for additional effect.
In PAD patients, a single course kept working for at least 5 years: the benefit was still present at the last assessment of the 5-year follow-up (Deev, 2018). Five years is where the study ended, not where the effect was seen to stop, and no data yet extends beyond that window. We recommend reinjecting at around 3 years to maintain the maximum effect.
VEGF plasmid therapy has one of the most comprehensive safety databases of any gene therapy: over 20,000 patients treated and on the market since 2012. In the 5-year and 10-year follow-ups the investigators recorded no adverse events they attributed to the plasmid and no impaired vision, and no individual disease occurred significantly more often than on standard therapy. Serious events did occur in both arms of the 5-year study, including one fatal metastatic renal cancer in the treatment group against none in the much smaller control group; that difference was not statistically significant. The plasmid stays outside your chromosomes, and integration is very inefficient.
No increase has been demonstrated, and the argument rests on how much VEGF actually reaches the rest of the body. VEGF can help an existing tumor build a blood supply, but a brief local rise is not the same as starting one. After intramuscular plasmid injection, median plasma VEGF rose about 8% at day 7 and was back to baseline by day 14 (Freedman, 2002, n=34). Long-term follow-up of local VEGF gene transfer, at 5 and 10 years for this plasmid and at 8 and 10 years for others, found no statistically significant excess of cancer (Deev, 2018; Chervyakov, 2023; Muona, 2012; Hedman, 2009). Those cohorts are small, so they rule out a large effect rather than a small one.
VEGF gene therapy is available in our partner clinics in Próspera (Roatán, Honduras), Mexico and Bahamas. Reach out and the Unlimited Bio team will walk you through the details.
References
- Deev RV, Bozo IY, Mzhavanadze ND, et al. pCMV-vegf165 intramuscular gene transfer is an effective method of treatment for patients with chronic lower limb ischemia. Journal of Cardiovascular Pharmacology and Therapeutics, 2015;20(5):473-482. doi:10.1177/1074248415574336
- Deev R, Plaksa I, Bozo I, Isaev A. Results of an international postmarketing surveillance study of pl-VEGF165 safety and efficacy in 210 patients with peripheral arterial disease. American Journal of Cardiovascular Drugs, 2017;17(3):235-242. doi:10.1007/s40256-016-0210-3 · PMC5435773
- Deev R, Plaksa I, Bozo I, et al. Results of 5-year follow-up study in patients with peripheral artery disease treated with PL-VEGF165 for intermittent claudication. Therapeutic Advances in Cardiovascular Disease, 2018;12(9):237-246. doi:10.1177/1753944718786926 · PMC6116753
- Chervyakov YuV, Staroverov IN, Moskovskiy IA, Lonchakova OM, Istomin AV. Ten-year results of conservative treatment of patients with infrainguinal occlusive disease using VEGF165 plasmid construct. Russian Journal of Cardiology and Cardiovascular Surgery, 2023;16(1):110-117. doi:10.17116/kardio202316011110
- Freedman SB, Vale P, Kalka C, et al. Plasma vascular endothelial growth factor (VEGF) levels after intramuscular and intramyocardial gene transfer of VEGF-1 plasmid DNA. Human Gene Therapy, 2002;13(13):1595-1603. doi:10.1089/10430340260201680
- Ledwith BJ, Manam S, Troilo PJ, et al. Plasmid DNA vaccines: investigation of integration into host cellular DNA following intramuscular injection in mice. Intervirology, 2000;43(4-6):258-272. doi:10.1159/000053993
- Martin T, Parker SE, Hedstrom R, et al. Plasmid DNA malaria vaccine: the potential for genomic integration after intramuscular injection. Human Gene Therapy, 1999;10(5):759-768. doi:10.1089/10430349950018517
- Muona K, Mäkinen K, Hedman M, Manninen H, Ylä-Herttuala S. 10-year safety follow-up in patients with local VEGF gene transfer to ischemic lower limb. Gene Therapy, 2012;19(4):392-395. doi:10.1038/gt.2011.109
- Hedman M, Muona K, Hedman A, et al. Eight-year safety follow-up of coronary artery disease patients after local intracoronary VEGF gene transfer. Gene Therapy, 2009;16(5):629-634. doi:10.1038/gt.2009.4
- Forster R, Liew A, Bhattacharya V, Shaw J, Stansby G. Gene therapy for peripheral arterial disease. Cochrane Database of Systematic Reviews, 2018;2018(10):CD012058. doi:10.1002/14651858.CD012058.pub2
Disclaimer
Gene therapies described on this website are experimental and not approved by the FDA. Effects are not guaranteed, and individual results may vary. Therapies are provided by third parties in Próspera ZEDE (Roatán, Honduras), Mexico and the Bahamas; Unlimited Bio is not a medical provider. Always seek the advice of a qualified healthcare provider with any questions you may have regarding a medical condition or treatment.