Dompé’s Marcello Allegretti discusses nerve growth factor research in eye and neurological conditions, including cerebral palsy, and how clinical trials measure meaningful improvements.
Nerve growth factor (NGF) is a protein naturally produced by the body that helps nerve cells grow, survive and function. It also plays a role in tissue healing. Researchers have explored its potential in eye diseases, nerve injuries and conditions affecting the brain, but producing NGF as a medicine and delivering it to the right tissues have been challenging.
In an exclusive Xtalks Clinical Edge interview, Marcello Allegretti, Chief Scientific Officer at Dompé Pharmaceuticals, discussed how research into corneal nerve damage helped establish NGF as a treatment and opened new possibilities in neurological diseases.
He also shared what scientists are learning about intranasal delivery, the questions being investigated in children with cerebral palsy and why clinical trials need to consider how improvements affect patients’ everyday lives.
Chief Scientific Officer
Dompé Pharmaceuticals
How NGF Research Found Its Starting Point in the Eye
When Marcello began working with NGF in 2010, scientists already understood much of its role in nerve development, survival and communication. However, turning this knowledge into therapies had proved difficult.
Marcello recalled that “the excitement was not corroborated by clear results despite the many attempts that were made.”
He believed two things needed attention, one was delivering NGF to affected nerve tissues and the second, was developing a reliable manufacturing process for the protein.
The cornea, the clear surface at the front of the eye, offered a good place to start. “Our primary interest was the application in [corneal] diseases because it’s an accessible tissue in which it’s also the most innervated tissue in the whole body,” he explained.
“So when you start working on something like this, you know that it’s only the starting point and you will learn more and more.”
– Marcello Allegretti
Dompé initially focused on neurotrophic keratitis, a rare condition in which nerve damage affects the cornea’s ability to maintain and repair itself. The nerve damage can have different causes, including diabetes, viral infections and surgery.
Marcello said that NGF’s effects on corneal healing were observed across patients with different underlying causes of nerve damage. This research helped establish the therapeutic use of cenegermin (Oxervate), an NGF-based eye drop approved by the FDA in 2018 for neurotrophic keratitis.
Dompé is now studying cenegermin in another eye condition, persistent corneal epithelial defect (PCED), where a wound on the cornea fails to heal properly. An ongoing Phase III study is evaluating whether the treatment can help these wounds heal.
Marcello recalled Nobel laureate Rita Levi-Montalcini’s comparison of discovering NGF to finding the tip of a sunken continent.
“So when you start working on something like this, you know that it’s only the starting point and you will learn more and more,” he said.
Get industry leading pharma and biotech news, events and expert insights delivered to your inbox.
Can Intranasal Delivery Bring NGF Closer to the Nervous System?
Eye drops can reach the cornea, but they do not efficiently deliver NGF to deeper structures, such as the back of the eye. Researchers have therefore been looking at other ways to reach these tissues.
One approach is intranasal delivery, where a treatment is administered through the nose. Scientists are investigating whether this route could help certain proteins reach or act within the central nervous system (CNS), potentially overcoming some limitations of the blood-brain barrier, which restricts the movement of many substances from the blood into the brain.
Marcello was initially skeptical about using intranasal delivery for proteins such as NGF. “Personally, I think this is not a general route,” he said.
However, his research led him to see its potential for certain proteins, depending on their biological properties.
Dompé has since advanced intranasal cenegermin into a Phase III study for non-arteritic anterior ischemic optic neuropathy (NAION), a condition in which reduced blood flow damages the optic nerve and can cause sudden vision loss.
The trial is investigating whether treatment can improve vision in affected patients.
Cerebral Palsy and the Question of Treatment Timing
Dompé is also studying intranasal NGF in cerebral palsy, a group of conditions that affect movement and posture due to injury or abnormal development of the brain early in life. Children’s physical abilities and needs can change as they grow.
The company’s ongoing Phase II trial in Italy involves children with spastic cerebral palsy, a form of the condition associated with muscle stiffness and difficulty moving.
The study is investigating whether NGF could help children who have already been living with the effects of an earlier brain injury.
“I think it will be an important proof of concept for the intranasal platform for sure, but also for the therapeutic potential in chronic condition,” said Marcello.
Scientists want to learn whether NGF could have therapeutic effects even years after the original brain injury occurred.
“We want to use a platform approach, let me say, but we need to customize the readout based on the patient population and the specific characteristics of the disease.”
– Marcello Allegretti
Marcello explained that researchers are selecting children at comparable stages of the condition so they can assess changes in function more consistently.
He also discussed hypoxic-ischemic encephalopathy (HIE), a form of brain injury caused by insufficient oxygen and blood flow, and traumatic brain injury (TBI). In these conditions, treatment soon after the injury could offer a different opportunity to investigate NGF’s therapeutic potential.
Measuring Improvements That Children and Families Can Recognize
Measuring the benefits of neurological treatments can be complicated, particularly when patients experience different symptoms and levels of disability.
For cerebral palsy, clinical trials use established scales to assess motor function, including movement and physical abilities, as well as cognitive function.
Researchers need statistically significant results while also understanding whether the improvements are noticeable in patients’ daily lives.
Dompé’s cerebral palsy study also includes assessments informed by parents and caregivers, whose observations can help researchers understand whether improvements are noticeable in everyday activities.
For NAION, they are evaluating changes in vision.
“We want to use a platform approach, let me say, but we need to customize the readout based on the patient population and the specific characteristics of the disease,” he said.
Looking back on his experience with NGF, Marcello was surprised by how many questions still needed answers in a field where the underlying biology was already well understood. Some of the most unexpected ideas, he reflected, came from asking simple scientific questions.
Join or login to leave a comment
JOIN LOGIN