According to a recent article, the nonprofit Gilbert Family Foundation has offered to fund the $5.4 million clinical study to better understand vision loss from NF1-associated optic pathway gliomas (NF1-OPGs).

Neurofibromatosis

Neurofibromatosis is a rare genetic disorder of the nervous system. The nervous system mainly affects how nerve cells form and grow, but neurofibromatosis causes tumors to form on the healthy nerve tissue. Usually, these tumors are benign, but sometimes they can become cancerous.

There are three types of neurofibromatosis, which are distinguished based on the characteristic symptoms and sometimes genetic testing:

• Type 1 (NF1): causes skin changes and deformed bones; usually starts in childhood with the symptoms present at birth
• Type 2 (NF2): causes hearing loss, ringing in the ears, and poor balance; symptoms often start in the teen years
• Schwannomatosis: causes intense pain; the rarest type

Neurofibromatosis is caused by genetic defects (mutations) that are either inherited or spontaneously occur. The specific genes that are involved depend on the type of neurofibromatosis.

• Type 1: The NF1 gene is mutated, causing a loss of the protein neurofibromin, which normally helps regulate cell growth
• Type 2: The NF2 gene is mutated, causing a loss of the protein merlin, which leads to uncontrolled cell growth
• Schwannomatosis: There are mutations in either the SMARCB1 gene or NF2 gene

The inheritance pattern for NF1 and NF2 is autosomal dominant, but the inheritance pattern for schwannomatosis is less clear.

Symptoms:

Additional signs and symptoms of neurofibromatosis (by type) are the following:

• Type 1
  • Flat, light brown spots on the skin and freckling in the armpits or groin area
  • Tiny bumps on the iris of the eyes
  • Soft bumps on or under the skin (neurofibromas)
  • Bone deformities
  • Larger than average head size and short stature
  • Learning disabilities
• Type 2
  • Gradual hearing loss, ringing in ears
  • Poor balance or headaches
• Schwannomatosis
  • Tumors on the skull, spinal and peripheral nerves
  • Numbness or weakness in various parts of the body
  • Loss of muscle

The Gilbert Family Foundation

The Gilbert Family Foundation is a nonprofit that was founded by Jennifer and Dan Gilbert. The goal of the foundation is to find a cure for neurofibromatosis type 1 (NF1). It accomplishes this goal through supporting cutting-edge research. In 2019, the foundation launched its Vision Restoration Initiative which funded research for developing therapies to repair or replace damaged visual systems as a result of NF1-OPGs (tumors).

The Study

The study, titled “Identifying Biomarkers for Visual Restoration Strategies in NF1-OPGs”, will be led by researchers at the Children’s Hospital of Philadelphia and the Stanford University School of Medicine. It will look at the mechanisms of vision loss as a result of NF1-associated optic pathway gliomas.

20% of children diagnosed with NF1 develop a tumor in their visual pathway (OPG). This can cause vision loss that is permanent and ranges from mild deficit to complete blindness. The study aims to define the structural, functional, metabolic, and patient-reported parts of NF1-OPG vision loss. This will then help develop future therapies, check the validity of existing models of the disease, and identify new metrics for evaluating the efficacy of vision restoration treatments.

Robert Avery, DO, Pediatric Neuro-Ophthalmologist at the Children’s Hospital of Philadelphia and Assistant Professor of Ophthalmology and Neurology at the Perelman School of Medicine at the University of Pennsylvania and Jeffrey Goldberg, MD, PhD, Professor and Chair of Ophthalmology at Stanford University School of Medicine, will be leading the study.

Lasting for around 3 years, the study will begin patient recruitment in either late 2021 or early 2022. Medical professionals are excited to take another step closer to their goal of preventing and possibly even reversing vision loss that results from these tumors.