ALGYL GGP - PRODUCT PROFILE

A key component of OA etiopathogenesis is a disorder of articular cartilage metabolism, in which the balance between catabolic and anabolic processes is disrupted. This primarily affects the metabolism of hyaluronic acid, whose role is to reduce friction between joint surfaces, and collagen, which is the basic component of intra-articular cartilaginous structures—that is, all joint surfaces, as well as subchondral bone. Under physiological conditions, these processes are balanced: newly formed HA and collagen in the joint replace the loss of these substances caused by catabolism. In OA, this balance is disturbed. Chondrocytes in the cartilage of the affected joint produce less and less hyaluronic acid and collagen. Increased activity of matrix metalloproteinases leads to cartilage destruction; inflammatory and reparative changes develop secondarily, intra-articular surfaces thicken, friction increases, and symptoms appear—pain and impaired joint function. As the disorder of joint metabolism and other pathological processes progress, symptomatology worsens.

OA is therefore characterized by a complex etiopathogenesis involving a combination of degenerative, inflammatory, and reparative processes affecting articular cartilage and other joint structures, including the synovium, subchondral bone, ligaments, and tendons.¹

CHARACTERISTICS

Algyl GGP is an innovative intra-articular product for the treatment of OA. Based on the latest knowledge about the complex etiopathogenesis of OA, the manufacturer designed a multi-component product that makes it possible to influence the main pathological changes responsible for symptoms in patients with this disease. Algyl GGP contains a patented gel complex composed of hyaluronic acid (in the form of sodium hyaluronate) and a combination of three components referred to as “GGP” (according to the initial letters of the substances): glucosamine (in the advantageous form of N-acetylglucosamine, which is more effective and safer than commonly used glucosamine derivatives), as well as glycine and proline (important amino acids that are essential for cartilage protection, especially for collagen synthesis). As excipients, the product contains phosphate buffer (NaH2PO4, Na2HPO4) and isotonic saline solution (NaCl, Aqua pro injectione).

The effects of the individual components complement each other and simultaneously act against several pathogenetic processes of OA. This enables the product to achieve more pronounced results than traditionally used single-component preparations. The complex contained in Algyl GGP penetrates the affected tissue and remains active there long enough to effectively influence the key pathophysiological processes associated with OA progression. This complex acts at the cellular level, stimulates the production of collagen and other key extracellular matrix components, and thereby supports articular cartilage regeneration. In addition, it modulates inflammatory processes in the synovial membrane, reducing pain and improving joint function. Thus, the product acts not only symptomatically, but also contributes to tissue regeneration.

The product is intended for intra-articular injection treatment of osteoarthritis, to increase joint viscoelasticity and for reconstruction of articular cartilage or supplementation of synovial fluid in joints.

EFFECTS OF THE PRODUCT COMPONENTS

Hyaluronic Acid

Hyaluronic acid (HA) is one of the main components of synovial fluid and the extracellular matrix. The main effects of HA include maintaining hydration and lubrication of joint surfaces, organizing proteoglycans in the extracellular matrix, and other roles, including support of cell migration and maintenance of a non-inflammatory joint environment. Intra-articularly administered HA improves the elasticity and viscosity of the intra-articular environment. It contributes to shock absorption via synovial fluid and ensures a sufficient layer around nociceptors, which reduces joint pain. HA also stimulates the metabolic activity of chondrocytes, for example increasing endogenous synthesis of glycosaminoglycans (including endogenous HA) and deposition of these physiological cartilage components into the extracellular matrix.

Thus, intra-articular application of HA not only replenishes the joint and compensates for the loss of this substance in the joint, but also increases physiological processes that supplement HA through endogenous synthesis.

Protection of joint tissues is also supported by the inhibitory effect of HA on enzymes that are one of the causes of joint destruction in OA. It also has a certain anti-inflammatory effect and reduces the production of nociceptive mediators. The benefits of HA in the treatment of OA have been repeatedly demonstrated, from basic laboratory studies to large clinical trials and systematic reviews.²⁻⁴

N-Acetylglucosamine

To increase the efficacy of products used in OA treatment, it is beneficial to combine components so that their effects complement each other. Algyl GGP therefore contains components that support articular cartilage regeneration, but also provide additional beneficial effects that contribute to the product’s complex action. One important component is the glucosamine derivative N-acetylglucosamine (NAG). The choice of this substance is justified: studies have shown that NAG is particularly advantageous in OA treatment.

NAG has a larger and more complex molecule than the commonly used chondroprotective agents (glucosamine sulfate and glucosamine hydrochloride), has a different metabolism, and is more effective and safer. Unlike these commonly used forms of glucosamine (which carry a risk of insulin resistance and progression of diabetes), NAG does not affect glucose metabolism and is therefore safe. After intra-articular application, NAG remains in the joint space relatively long, where it contributes to cartilage tissue regeneration. It triggers activation of chondrocytes and synthesis of glycosaminoglycans and proteoglycans, which contribute to cartilage regeneration. Thus, NAG activates chondrocytes to synthesize proteoglycans and glycosaminoglycans, the building blocks of cartilage.

In addition, it has been shown to inhibit matrix metalloproteinases, i.e., enzymes that deepen degeneration of articular cartilage. It activates the enzyme hyaluronan synthase-2 and thereby supports the body’s own biosynthesis of HA in the joint (which is another advantage over common glucosamine forms). It reduces the production of pro-inflammatory cytokines in cartilage. NAG therefore has not only chondroprotective but also anti-inflammatory effects and acts comprehensively against the etiopathogenetic process of OA. The usefulness of NAG has been confirmed in clinical studies demonstrating both its efficacy and high safety.⁵⁻⁷

Glycine

Research has shown that, in addition to degenerative and inflammatory processes, changes in the distribution (and metabolism) of amino acids in connective tissue are also involved in the etiopathogenesis of OA. This particularly concerns glycine and proline, which form the basic components of collagen, the fundamental component of the intercellular substance of cartilage. Both amino acids are also involved in other processes ensuring antioxidant and anti-inflammatory protection of joint tissues. OA progression is often associated with a deficiency of these amino acids.

The effect of glycine and proline against OA progression has been documented in a number of studies. Glycine, as an important substrate for collagen synthesis, is synthesized to some extent in the body, but this amount is not sufficient for collagen synthesis. Glycine is highly flexible due to the small size of its molecule, which allows it to fit into the tightly compressed center of the collagen helix. In collagen, glycine represents every third amino acid residue. The structure of glycine enables three polypeptide chains to approach each other, which is necessary for the stability and structure of the collagen triple helix. The presence of glycine in every third position of the collagen sequence is critical for proper folding and stability of collagen molecules. Without glycine, collagen would not be able to form its characteristic structure, which is necessary for its function as a structural protein in joints.

It is also a component of an important substance for joint lubrication and shock absorption—proteoglycan-4 (lubricin), a glycoprotein formed in synovial fibroblasts. Glycine has additional beneficial effects: it acts anti-inflammatory and antioxidant. Therefore, in patients with OA, where collagen catabolism predominates, it is appropriate that glycine is part of the treatment.⁸⁻⁹

Proline

Like glycine, proline is an amino acid necessary for collagen synthesis in chondrocytes. Proline is produced in limited amounts in the body, but during established osteoarthritis its amount is insufficient for regeneration of joint tissues, especially collagen. Biosynthesis of proline needed for collagen synthesis is a relatively complex process, and in already developed OA this amino acid is not available in sufficient quantity.

Proline is important not only for adequate collagen synthesis and thus cartilage regeneration, but also has anti-inflammatory and immunomodulatory effects that are important in counteracting pathophysiological processes causing OA progression. Dysregulation of proline metabolism is a common component of connective tissue diseases, including OA. Proline plays an important role in regulation of gene expression, transcription factors, cellular signaling, and cellular redox reactions—not only in collagen synthesis but also in the synthesis of other substances important for the physiological condition of connective tissue. It also has antioxidant and anti-inflammatory effects that contribute to reducing OA severity. It supports proliferation and differentiation of chondrocytes, facilitates regeneration of articular cartilage, and contributes to regulation of bone metabolism balance. As with glycine, a higher incidence of proline deficiency has been found in OA patients compared with the healthy population. Therefore, the application of proline has a logical place in Algyl GGP.¹⁰⁻¹¹

EFFICACY AND SAFETY OF THE PRODUCT

The efficacy of Algyl GGP, which contains a patented gel with the combination HA + NAG + Glycine + Proline,¹² has been investigated and confirmed in studies that demonstrated its efficacy both in comparison with single-component hyaluronic acid and in clinical practice, which confirmed not only its efficacy but also its safety.

Contraindications for the product include hypersensitivity to its components, skin infection at the intended injection site, infection of the affected joint, and bleeding disorders.

Study Confirming Efficacy

A laboratory study conducted at the Clinic of Orthopedics and Traumatology in Istanbul showed that Algyl GGP for treatment of knee OA is significantly more effective not only compared with physiological saline, but also compared with single-component HA. The efficacy of Algyl GGP was objectively demonstrated by histological examination, which showed that application of Algyl GGP in monosodium acetate-induced osteoarthritis of the knee led to regression of degenerative cartilage changes. This effect was substantially more pronounced than with single-component HA.¹³

The regenerative effect of Algyl GGP in this study is documented by microphotographs of cartilage sections from the knee joint in:

1. the group receiving physiological saline,

2. the group receiving hyaluronic acid,

3. the group receiving Algyl GGP.

Confirmation of Efficacy and Safety in Clinical Practice

Algyl GGP has been used in orthopedic practice in more than 200,000 patients with OA and proved to be effective, safe, and long-lasting. Long-term monitoring of patients treated with this product shows that it not only provides symptomatic pain relief, but also improves cartilage quality and reduces the need for further pharmacological or surgical interventions. In patients with early-stage OA, slower progression of degeneration was observed, and in some patients even improvement in the structural integrity of the joint occurred, as confirmed by MRI findings.

These extensive practical data form the basis of the manufacturer’s Safety Report for Algyl GGP, which confirms that in 200,000 applications in patients with knee OA, no adverse effects occurred, such as joint pain or swelling, injection-site reactions, or other complications.¹⁴

CLINICAL STUDY

A prospective, randomized, blinded study¹⁵ was conducted at two clinical sites in Istanbul (Turkey), comparing the efficacy of intra-articular administration of:

• hyaluronic acid alone (HA, Group 1),

• HA + Proline (Group 2),

• a four-component combination HA + Glycine + Proline + N-Acetylglucosamine (composition of Algyl GGP, Group 3).

The study included 111 patients with grade 2–3 knee osteoarthritis aged 40–80 years. In all patients, the following were assessed before injection and at 2, 8, and 12 weeks after administration:

• WOMAC index (pain, stiffness, and physical function),

• Lequesne algofunctional index,

• visual 10-point analog scale (VAS) for joint pain during movement.

The results showed that in all groups there was, on average, a significant improvement in the condition of the affected joint after administration of the respective products. In Group 3 (four-component combination HA + N-acetylglucosamine + Glycine + Proline), the improvement was more pronounced and longer-lasting. Between weeks 8 and 12 after injection, Groups 1 and 2 showed significant score fluctuations, while Group 3 maintained stable improvement (p>0.05).

After 12 weeks, Group 3 showed significantly lower (i.e., better) mean WOMAC, Lequesne, and VAS scores compared with Groups 1 and 2.

Regarding mean values of parameters such as Lequesne index and VAS, no differences were observed between Group 1 (HA alone) and Group 2 (HA + Proline), indicating that adding proline alone to HA is not sufficient to improve the effect. A clear difference appeared only with the four-component combination HA + N-acetylglucosamine + Glycine + Proline. This effect may be attributed to the ability of N-acetylglucosamine and the amino acids proline and glycine to increase type II collagen production, stimulate synthesis of hyaluronic acid and glycosaminoglycans, and support cartilage regeneration.

USE IN ORTHOPEDIC PRACTICE

Based on available studies and clinical experience, it can be stated that Algyl GGP represents a significant advance in the treatment of osteoarthritis and other degenerative joint diseases. Several key factors make this product a suitable choice for orthopedic practice:

1. Long-term effect: Unlike symptomatic drugs such as corticosteroids, Algyl GGP provides longer-term benefits due to its ability to support cartilage regeneration and modulation of inflammatory processes.

2. Safety: As demonstrated by orthopedic practice experience, Algyl GGP is well tolerated by most patients, making it a safe alternative to some other treatment methods.

3. Support of tissue regeneration: The regenerative properties of Algyl GGP are a major advantage, offering hope for improving quality of life in patients with chronic degenerative joint diseases such as OA.

Based on these findings, Algyl GGP can be recommended as a suitable treatment for OA patients seeking a comprehensive, safe, effective, and long-lasting therapy without significant side effects.

COMBINATION WITH OTHER PRODUCTS

The combination of Algyl GGP and PRP (platelet-rich plasma) may synergistically stimulate regeneration of cartilage and connective tissue, deliver increased levels of anti-inflammatory cytokines, and help relieve pain and swelling. PRP also contains growth factors for faster healing and regeneration. An important aspect of this combination is also stimulation of angiogenesis, i.e., formation of new vessels in the subchondral bone and surrounding tissue, which improves joint nutrition. This may improve overall joint biomechanics and prolong the treatment effect, potentially slowing progression of osteoarthritis through synergistic support of repair processes.

Nevertheless, repeated administration of Algyl GGP provides a comparable regenerative effect even without combination with PRP.

Fig. 4 (caption)

Changes in WOMAC score over time. Statistical significance of improvement after treatment: p<0.001 for all groups vs baseline. In Group 3, the effect at 12 weeks is significantly better than in Groups 1 and 2, indicating longer-lasting efficacy of the four-component product ALGYL GGP (similar results were also observed for the Lequesne index).

Fig. 5 (caption)

Changes in VAS pain score over time. In Group 3, the effect at 12 weeks is significantly better than in Groups 1 and 2, indicating longer-lasting efficacy of the four-component product ALGYL GGP.

Algyl GGP – Technical and Mechanical Specifications

Appearance: clear, transparent, yellowish, viscous gel
Particle size: < 0.02 μm
Density: 1.010 to 1.030 g/cm³
Color: ≤ 5.0 Pt-Co
Turbidity: < 1.0 NTU
Osmolality: 200–400 mOsm/kg
Bacterial endotoxin test (LAL): ≤ 1 EU/ml
Viscosity: 5 cp–50,000 cp
pH: 6.5 to 7.5

ALGYL GGP has a patented gel and the entire injection composition is patent-protected in terms of the combination and ratio of active substances. The molecular weight of HA in Algyl GGP is 1,200 kDa. This is HA at the lower limit of the high-molecular-weight range, which shows very good clinical results in terms of pain reduction, functional improvement, and cartilage protection. It represents an ideal compromise between efficacy and tolerability, as it is large enough to have mechanical and anti-inflammatory effects, but not too viscous to cause discomfort during administration. The HA used (sodium hyaluronate) is of synthetic origin; in its patented mixture, the manufacturer uses a raw material supplied by a French supplier. For administration, the manufacturer recommends, for example, using a 23G needle.

ADMINISTRATION PROCEDURE

• Algyl GGP is administered once every 6, 12, or 16 months, depending on disease severity; a second dose may be applied if needed. In acute conditions, 3 injections may be administered at 3-week intervals.

• In the case of joint effusion, aspiration of the exudate, immobilization, application of ice packs, and/or intra-articular corticosteroid administration are recommended to reduce the effusion. The medical device Algyl GGP is applied after 2–3 days.

• Based on clinical experience, Algyl GGP may be administered to several joints simultaneously, and therapeutic cycles may be repeated as appropriate.

• Algyl GGP may be applied in combination with PRP (platelet-rich plasma) to accelerate healing and regeneration.

• Product classification: Class III medical device