Fundamental Therapeutics for advanced wound healing
11 Dudhope Terrace, Dundee, DD3 6TS, UK

Our Science

The science and discoveries that have led to the founding of TRT are documented in a large number of scientific publications and patents. A selection of these publications are referenced on this page.

Introduction to TRTX

Horse ownership is widespread in most parts of the world and includes horses kept as work animals, racing animals and of course for recreation. It is costly to own a horse, and the value of a horse can vary enormously. The lifetime cost of caring for a horse varies depending on the horse’s role; thus, over a 25-year lifetime, owners can expect to spend:

  • $240,000-$1,000,000+ for competitive horses
  • $150,000-$400,000+ for recreational horses
  • $105,000-$290,000+ for backyard horses.

These figures do not include events or operating expenses.

The cost of treating a single leg wound can range from $500 – $7,000 depending on the severity of the wound. The financial impact of treating wounds on the equine industry is worth $150-$300 billion worldwide.

The global veterinary wound care market was valued at US$ 1.1 Billion in 2022 and is expected to reach US$ 2.8 Billion by 2033. The surgical wound care products segment with a market share of more than 61.0% has topped the global market within the product category in 2022 and is expected to grow at a CAGR of close to 8.5% over the forecast period (2023 to 2033). It is in this area that we believe TRTx will have a major impact.

The problem: Slow Healing, Excess Granulation Tissue or Proud Flesh

Wounds on horses’ bodies and limbs are exceptionally common. Those on distal (lower—below the knee/carpus or hock/tarsus) limbs are especially difficult to manage.

The tendency for limb wounds in horses to heal in a protracted manner is thought to stem from a compromised vascular supply due to the paucity of soft tissue underlying the skin in this anatomic location and from continued environmental contamination of the wound owing to its proximity to the ground. Due to inefficient blood vessel formation, limb wounds of horses are hypoxic during the inflammatory phase of repair. This hypoxia hampers the ability of leukocytes to clear foreign material and resist infection. Inflammation ensues and leads to delays, in wound contraction, epithelialization, and ultimately healing.

The same of lack of oxygen due to the reduced blood flow also plays a role in the development of excessive granulation tissue (EGT), also known as proud flesh. Physiologically, excessive granulation tissue grows until it protrudes from the site of injury, often resembling a tumour that further impedes wound healing.
EGT commonly develops in poorly contracting wounds, particularly in the leg of the horse, it prevents skin cells from covering wounds and interferes with hair regrowth. EGT delays wound healing, is very difficult to treat, and can result in the loss of use of the horse.
Currently, there is no effective treatment to activate healing or to prevent EGT formation (i.e. the best protocol is to bandage the wound and control infection).  Excess granulation tissue can be removed through surgery; however, it reappears regularly. Underneath the granulation tissue, the wound remains unhealed.

The Unique Solution Provided By TRTx

TRTx wound healing support gel is an advanced treatment accelerates the speed of wound closure, and reduces the risk of EGT formation.

The Science Behind TRTx

TRTx wound healing support gel is based on a patented organic molecule designed by University Professors in New Zealand and Scotland. This unique molecule mimics the protein-protein interactions that take place naturally during normal wound healing on the surface of endothelial cells and fibroblasts. Effectively, this molecule kick-starts the wound healing process in difficult situations (i.e. poorly contracting horse limb wounds), at very low concentrations. This treatment causes the wound to generate new blood vessels, speeds up wound closure and avoids the formation of proud flesh.

TRTx wound healing support gel mimics proteins expressed during the normal wound healing process. TRTx interacts with cellular receptors on the surface of skin and cells within the body (endothelial) cells, and a signalling cascade gets initiated that tells the endothelial cells, and fibroblasts to migrate which starts the blood vessel formation process (angiogenesis). Once angiogenesis gets started, wound closure can take place.

TRTx wound healing support gel and cells

In-vitro data shows that the active compound in TRTx wound healing support gel (TRTx) can induce cell migration at low concentrations different assays. The graph shows a comparison of cell migration (fibroblasts). The data is expressed as fold-stimulation of migration relative to control fibroblasts in the absence of test compound.
The baseline (control) migration is indicated by the horizontal dotted lines, and results from an inactive control substance (inverted triangles).
TRTx (dark circles) stimulates cell migration with a bell-shaped dose response (note that the concentration axis is a log scale) analogous in potency and profile to that of the proteins expressed during wound healing (white circles).

TRTx wound healing support gel’s effect on genes.

Gene expression analysis using RT2 Profiler Arrays (Qiagen) was carried out using Human Dermal Fibroblasts to determine the effect that TRTx wound healing support gel has on gene activation. The results show that TRTx activates a gene involved in tissue repair and reepithelization, as well as a gene involved in crosslinking actin containing filaments in skeletal muscle.

TRTx’s effect on mouse models of wound healing

Based on TRTx’s excellent results in cell lines, the decision was made to move into animal models of wound healing. Two different diabetic mice models were chosen due to their proven value in assessment of impaired wound healing.

C57BLKs/Bom diabetic mice studies: The study involved 70 C57BLKs/Bom diabetic mice (divided into 10 groups of 7 animals each), which were surgically given a single standardised full-thickness wound (10mm x 10mm). The study showed that at concentrations of 1 ng/mL per cm2 TRTx is able to increase the speed of healing (wound contraction) whilst reducing scarring (excess granulation).

Diabetic mice BKS.Cg-m Dock7m +/+ Leprdb /J (db/db) studies: This is a more challenging model of wound healing model, and it involved 72 BKS.Cg-m Dock7m +/+ Leprdb /J (db/db) diabetic mice. A single standardised full-thickness wound (10mm x 10mm) was made, and the mice were treated with TRTx at three different doses. At a 100 picogram dose, the difference between controls and treated animals remained significant on day 20 (p=0.009), 14 days after the last dosage.

Overall, in diabetic mouse experiments, TRTx increased the speed of healing in compromised animal models by 77% ±3% levels based on comparative wound measurements in non-diabetic animal controls. Increased re-epithelialisation was also observed, with very high levels of wound re-epithelialisation (98%) obtained in the presence of femtomolar concentrations of TRTx.

Significantly, TRTx caused a reduction of mean granulation tissue depth in wounds relative to control groups (i.e. reduced scar formation).

The effects of TRTx on wound healing were investigated in diabetic mice BKS.Cg-m Dock7m +/+ Leprdb /J (db/db), a model of delayed wound healing. A single standardised full-thickness wound (10.0mm x 10.0mm) was created in the dorsal skin of each animal and these were divided randomly into 4 groups of 8-10 animals each. TRTx was applied in a gel (HPMC) at three different doses (20, 100 or 200 picograms per dose). The wounds received a single treatment of the appropriate dose on days 0, 2, 4 and 6 post-wounding (arrows). Controls received the gel alone at the same time. Image analysis software was used to calculate wound closure from images taken at regular intervals post-wounding. For each wound at each time point, open wound area was measured and expressed in terms of % wound area relative to day 0. Graphs show the mean and standard error for each group of animals. TRTx significantly stimulated wound healing at the three doses tested. P values are shown for the 100 picogram dose. At this dose, the difference between controls and TRTx-treated animals remained significant on day 20 (p=0.009), that is, 14 days after the last treatment with TRTx.

TRTx wound healing support gel and toxicity

TRTx wound healing support gel is based on a small molecular organic compound (TRTx), free of any biologicals, GM components, serums and cells. Furthermore, TRTx wound healing support gel requires only a few topical applications at a very small dose,

which makes it inherently safe. Pharmacokinetic data shows the rapid clearance of TRTx both in-vitro and in-vivo. In-vitro data shows that TRTx is rapidly cleared by female CD1 mouse microsomes (>16 mL/min/g liver) and is degraded in plasma within 30 min. We were not able to detect neither the parent nor the metabolic side product in the blood of female Balb/c mice after a 50 L subcutaneous injection of the compound at the therapeutic dose (5 ng/mL). Detection of the degradation side product was only possible when excess of a 400x dose of the side product was injected into the female Balb/c mouse. Thus, all evidence suggests that TRTx does not undergo systemic distribution.

TRTx and stability

TRTx Advanced Wound Healing Support Gel has been designed to be free of additives and preservatives. As such, the gel ingredients are purified NZ aqua (95%), hydroxypropyl methyl cellulose (4.99%), TRTx (5 ng/mL), and DMSO (0.00005%).
TRTx Advanced Wound Healing Support Gel has an excellent safety profile based on (a) absence of foreign biologicals or potential pathogens in its synthesis and manufacture; (b) unique mode of action requiring low doses and few applications; (c) lack of effect on cell division and preventing the formation of excess granulation tissue.
TRTx Advanced Wound Healing Support Gel has been tested for degradation and analysed for bacterial, yeast and mould growth at 25 and 35°C.

TRTx and horses

Four horses underwent surgical procedures to generate equal wounds on two legs at a position below the knee. Two surgical wounds, each 2.5 cm x 2.5cm (6.25 cm2), were made on the medial and lateral aspects of both fore limbs of all the horses (8 wounds per horse). The wounds were skin deep (i.e. did not go into the muscle), and the entire patch of skin was removed.

In total 32 wounds were created, 16 controls (untreated) and 16 treated with TRTx Advanced Wound Healing Support Gel. All wounds were treated using current best practice (compression) with and without TRTx Advanced Wound Healing Support Gel. Each horse had its own control.

At various time-points throughout the trial, the area of each wound was calculated and expressed as percentage of the original wound area (both from day 0 and from day 12, when the application of 5% gels started). The area (as percentage) of each treated wound was then compared with its corresponding untreated control. A difference of at least 1.4-fold between TRTx Advanced Wound Healing Support Gel treated and control wounds was considered significant.

TRTx Advanced Wound Healing Support Gel stimulated wound healing in each of the 4 animals tested. TRTx Advanced Wound Healing Support Gel stimulated wound healing in 6 out of 8 wounds. Significant stimulation was observed at 15 time points. The wound healing stimulation induced by TRTx Advanced Wound Healing Support Gel was considered statistically significant (p<0.001).

Wound area presented as % of initial wound area when treatment started. Each wound was compared to compared to the corresponding control (vehicle only, no TRTx Advanced wound support gel) a difference between wound sizes of at least 1.4- fold was considered significant. C = control wounds. T= TRTx Advanced Wound Healing Support Gel treated wounds. * show significantly different results.

TRTx and compliance

Due to its unique formulation, TRTx Advanced Wound Healing Gel received an exemption from the requirement of registration under the Agricultural Compounds and Veterinary Medicines (ACVM) Act 1997. The exemption is valid from the 03.11.21 to the 02.11.24.

TRTx Advanced Wound Healing Gel received Environmental Protection Agency Approval on the 09.02.23 (valid until the 09.02.26).

TRTx and manufacture

TRTx is manufactured in a facility in Christchurch, NZ. The manufacturing facility has GMP Certification (Cosmetic, Toiletry and Fragrance Association of New Zealand).


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