The drug, which was created thanks to the Nobel Prize-winning discovery, can help people with the so-called neurotrophic keratitis, an eye disease that can lead to blindness, ophthalmology experts say. Clinical trials of the drug are conducted, among others in two centers in Poland.
There is currently no effective treatment regimen for neurotrophic keratitis. The clinical trial currently conducted, also in Poland, is a chance for patients to receive effective therapy – said Prof. Edward Wylęgała, head of the Clinical Department of Ophthalmology at the Medical University of Silesia in Zabrze.
It is one of the two centers that recruits patients for the REPARO study. The second is the Chair and Clinic of Ophthalmology, II Faculty of Medicine, Medical University of Warsaw, headed by prof. Jacek Szaflik.
The study tests drops containing the so-called recombinant (genetically engineered) human nerve growth factor – rhNGF. It is the counterpart of naturally occurring NGF, which was discovered in the 50s by the Italian researcher Rita Levi Montalcini. In 1986, Montalcini was awarded the Nobel Prize in Physiology and Medicine.
NGF is present in our body in the central and peripheral nervous system, but also in the blood, immune system, heart, liver, and the eye, e.g. in the cornea and optic nerve. It stimulates the growth, development and survival of neurons.
As prof. Hatching neurotrophic keratitis is a disease caused by the reduction or loss of innervation of the cornea – the best tissue in the human body (400 times more than the skin). The new therapy therefore acts directly on the cause of the disease.
According to prof. Stefano Bonini of the University of Rome, who coordinates the REPARO study, neurotrophic keratitis is a heterogeneous disease as it can develop as a consequence of many health problems.
The most common result is: inflammation of the cornea caused by viruses from the herpes family (including the virus that causes herpes simplex or the virus that causes chickenpox and shingles), chemical burns to the surface of the eye, abuse or misalignment of contact lenses, diabetic neuropathy (damage to the nerves associated with with diabetes – PAP), AIDS, multiple sclerosis (MS), severe vitamin A deficiency, as well as some corneal surgeries, intracranial surgery due to cancer and the use of large amounts of certain medications – topical, such as drops containing large amounts preservatives, anesthetic or general drops, such as antihistamines or antipsychotics.
These factors cause damage or dysfunction of the optic nerve and its branches that innervate the cornea. In the beginning, the disease is usually asymptomatic. As it is accompanied by a disturbance, or even a complete lack of corneal sensation, the patient does not feel pain, and the only symptom that can be perceived is reduced visual acuity – explained Prof. She hatched. For this reason, the disease is usually detected in the advanced stages.
It is estimated that one in five thousand suffers from its severe form. people.
In the development of neurotrophic keratitis, the corneal epithelium is gradually lost, ulcerated and perforated. Disturbances in the blink reflex and tear secretion may also appear, which further intensify the inflammatory processes and damage to the cornea. Moreover, ulcers can become superinfected by bacteria, viruses and fungi, especially in diabetic patients. The consequence of the disease may be corneal clouding and loss of vision – said Prof. Bonini.
According to prof. John Dart from the University of London Collegium, who is researching a new drug in Great Britain, currently there are no good treatments for the disease, in addition to targeting the cause of its development.
In the initial stage of the disease, moisturizing drops without preservatives are used to improve the condition of the corneal epithelium and prevent the progression of the disease. It is also imperative that you eliminate all the risk factors that you can influence.
In case of greater damage to the cornea, a dressing lens can be used, or an amniotic membrane dressing can be applied to the surface of the cornea, and antibiotics are also used to prevent superinfection of the lesions. In more severe disease, surgical methods are used, such as suturing the eyelid or paralysis of the upper eyelid with botulinum toxin (this is to protect the cornea against drying out and the action of external factors). When corneal perforation occurs, a transplant may be a rescue, but in patients with this disease it is not a very effective method – assessed Prof. Darts.
Therefore, scientists have high hopes for the rhNGF drops that have just been tested.
The research carried out in the 90s by the team of prof. Bonini in a group of over 100 patients indicated that NGF may help in the treatment of neurotrophic keratitis as well as other eye diseases.
However, we used a mouse version of NGF at that time, which could not become a drug – emphasized Prof. Bonini. For this reason, scientists from one of the Italian biotechnology companies have developed a method of producing rhNGF by genetically modified bacteria.
Phase I of the REPARO study enrolled 18 patients (male and female) with moderate to severe disease. These were patients who were not helped by the currently available methods of therapy. For eight weeks they were given either drops with rhNGF – at a dose of 10 micrograms per milliliter (mcg / ml) or 20 mcg / ml, or a placebo.
The results of this phase of the study are very promising – assessed Prof. Bonini. He noted that in most patients who received the drug, complete healing of the cornea and improvement in its sensitivity (i.e. restoration of innervation) were noted. Thanks to the therapy, patients regained visual acuity.
Prof. Dart cited the example of a patient who was administered the drug outside of the study, thanks to which her only working eye was saved. Currently, she does not use any treatment, her vision has improved and she was able to return to normal life – emphasized the specialist.
According to prof. It is also important that the drug is well tolerated by the surface of the treated eye.
The second phase of the REPARO study is currently underway. It is conducted in 39 ophthalmic centers in nine European countries, including Poland. Patients who will take part in the study will receive either one of the two doses of the drug or a placebo. Neither the sick nor the investigators will know what the person is getting. The safety and effectiveness of the therapy are to be monitored from 48 to 56 weeks.
Importantly, if the patient’s cornea does not improve after a few weeks, scientists will check what is being given to him and if it is a placebo, the patient will be switched to the drug.
I hope that this is a therapy that will prevent corneal clouding and, consequently, loss of vision in many patients, emphasized prof. She hatched.
Currently, the effectiveness of the drug is also tested, among others in patients with dry eye syndrome and in people with retinitis pigmentosa, a genetic condition that inevitably leads to blindness. (PAP)