OTL-200 for Metachromatic Leukodystrophy Investigational New Drug Application Gets Approved


In a recent press release, gene therapy company Orchard Therapeutics (“Orchard”) announced that the FDA approved Orchard’s Investigational New Drug (IND) application for OTL-200. This gene therapy solution is designed for patients with metachromatic leukodystrophy (MLD). Because the FDA approved the IND, Orchard can now hold clinical trials and administer this investigational treatment to humans.


Over the years, Orchard has worked to create targeted gene therapy solutions for patients with rare diseases. The company uses an ex vivo model, meaning that cells are genetically modified outside of the body before being administered. This is in contrast to in vivo models, which modify the cells in the body.

In this case, OTL-200 is an autologous, hematopoietic stem cell (HSTC), lentiviral vector gene therapy. Let’s break that down a little:

  • Autologous means that it uses cells or tissues from the same person. In this case, HSTCs are sourced from the patient themselves. Next, OTL-200 inserts a working copy of the mutated or defective gene before the cells are transplanted back in the body.
  • Hematopoietic stem cells help produce and develop healthy blood cells.
  • Lentiviral vectors, as described by GeneTherapyNet, are:

a genus of the Retroviridae family, characterized by a long incubation period. Lentiviruses can deliver a significant amount of genetic information into the DNA of the host cell, so they are one of the most efficient methods of gene delivery vector.

So, in short, OTL-200 uses lentiviral vectors to deliver functional genes to patients using their own HSTCs. Orchard included data sourced from 39 patients in the IND. Additionally, Orchard applied for Regenerative Medicine Advanced Therapy designation, but this has not yet been approved.

Metachromatic Leukodystrophy (MLD)

Overall, metachromatic leukodystrophy (MLD) exists under the umbrella of leukodystrophy, groups of progressive central nervous system (CNS) disorders characterized by the destruction of the myelin sheath. Normally, the myelin sheath acts as a protective coating for nerve cells. But patients with metachromatic leukodystrophy experience destruction of this myelin sheath, exposing and damaging nerve cells. Typically, this disorder is caused by ARSA gene mutations. However, in rarer cases, a PSAP gene mutation may cause symptoms.

There are three main forms of metachromatic leukodystrophy: late-infantile, juvenile, and adult. Late-infantile is the most common form of the disorder. Around 50% of all diagnoses fit into this category. Typically, this form is fatal within 5 years for about half of all patients. Next, the juvenile form consists of around 20-30% of all diagnoses. Symptoms of juvenile metachromatic leukodystrophy typically occur between ages 4 and 14. It is typically fatal within 10 years for 44% of patients. Finally, the adult form is the least common.

The gene mutations which cause this condition result in an accumulation of sulfatides in the brain, kidneys, spleen, liver, and gallbladder. It is this buildup which ultimately causes neurodegenerative damage. While symptoms vary based on forms, common symptoms include:

  • Changes in mood, behavior, or personality
  • Seizures
  • Intellectual and developmental delays
  • Motor issues
  • Difficulty speaking or walking
  • Muscle spasms and/or muscle weakness
  • Blindness
  • Periventricular leukomalacia, a form of brain damage present in late-infantile metachromatic leukodystrophy
  • Impaired balance and coordination
Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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