MACULIA platform

THE MACULIA PLATFORM TARGETS INTERMEDIATE DRY FORM ARMD. BIOPHYTIS HAS ACHIEVED VERY SIGNIFICANT RESULTS IN VIVO WITH TWO FAMILIES OF COMPOUNDS, WHICH HAD PROVEN THEIR SAFETY.

THE OXIDATIVE STRESS CAUSED BY A2E LEADS TO RETINAL CELL DEATH

All photoreceptors contain a visual pigment that absorbs some of the spectrum’s radiation, and it is this absorption of photons that is at the origin of the nerve messages they emit. Each visual pigment molecule consists of a protein called opsin and a non-protein molecule : retinal. Under the effect of light, the retinal is isomerised and detaches from the opsin. This return to its original form, which is essential to its activity, brings into play a sequence of reactions for which photoreceptors and the retinal pigment epithelium (RPE) are jointly responsible.

Maculia-TL

This protection mechanism does however have a downside when, following a malfunction (associated with age or genetic defects), a molecule called A2E accumulates in large quantities in the cells of the RPE. In fact, in the presence of (blue) light and oxygen, A2E oxidises some or all of its double bonds and the molecules thus formed react with various cellular constituents, thereby disrupting the activity of the RPE and, in particular, its activity involving the digestion of fragments of photoreceptors. Because of this, the RPE cells accumulate the waste products, leading to a malfunction of the metabolism and of the various signalling pathways, which in turn leads to the death of retina cells.

A MOLECULAR TARGET AT THE CENTRE OF THE PATHOLOGY MECHANISM

MACUNEOS is capable of linking to PPARa with a good level of affinity. Recent data attributes an important role to this class of nuclear receptors, the PPARs (Peroxisome-Proliferator Activated Receptors) in protecting against ARMD.

Through this mechanism, the protection provided by MACUNEOS can be envisaged at many levels which are mutually compatible:

  • MACUNEOS has a filtration role in absorbing blue light,
  • MACUNEOS reduces the capture of (exogenous) A2E by RPE cells,
  • MACUNEOS has an antioxidant effect,
  • MACUNEOS has an anti-inflammatory and anti-VEGF action,
  • MACUNEOS protects against apoptosis.

CONCLUSIVE IN VITRO AND IN VIVO TESTS

Many series of tests have been conducted on mice and rats under experimental conditions reproducing ARMD. The candidates were tested with intravitreal injection, intraperitoneal injections and by oral administration.

In an intravitreal injection test, MACUNEOS showed a very significant protective activity. The activity of the photoreceptors is measured by electroretinography, and the condition of the retina can be assessed using histology.

schémas-Biophytis-V5_English20
Number of layers of photoreceptors in the presence of MACUNEOS
or of a control in an animal model of ARMD

By oral administration, MACUNEOS proved to be effective, maintaining a normal electroretinogram (whereas this deteriorated in animals without the supplement). In addition, the eyes of animals having ingested MACUNEOS contained reduced quantities of A2E.

schémas-Biophytis-V5_English12

Response of the retina to a light signal measured by electroretinography
(ERG, b-wave) in the animal model of ARMD

A PRODUCT THAT HAS ALREADY BEEN CLINICALLY TESTED

The effects of a concentrated, titrated plant extract have been evaluated in a clinical trial following chronic oral administration for three months, confirming the absence of toxicity (no serious adverse events observed associated with the product) at the dosage studied. The active natural substance can be administered to the general population, as well as its metabolite circulating in human subjects.