Update on noncosmetic uses of botulinum neurotoxins

Introduction

Although botulinum neurotoxin type A (BoNT/A) has achieved notoriety for its role in the management of facial lines, its first clinical use was in ophthalmology in the 1980s. Over the years, the medical uses of BoNT/A have expanded to include selected conditions of muscular contractions, glandular secretions, and/or sensory symptoms such as pain, as listed in Table 1.1 . A BoNT product based on serotype B is also approved for several noncosmetic conditions (see Table 1.1 ). Collectively, these conditions benefit from the local action of BoNTs, which are injected into tissues such as muscle, skin, or glands where they act on specific nerve endings.

The first BoNT product developed for clinical use was onabotulinumtoxinA, originally known as Oculinum™ and later Botox®. This was followed by a BoNT type B product (rimabotulinumtoxinB; Myobloc®) and several other type A products, abobotulinumtoxinA (Dysport®) and incobotulinumtoxinA (Xeomin®). These medications are the main BoNT products approved for noncosmetic, medical use in major territories. As with all BoNTs, these medications are not interchangeable due to differences in manufacturing methods and doses, which are expressed in units of biological activity.

This chapter briefly describes the noncosmetic uses of BoNTs. The text generally focuses on conditions and approval history in the United States, but approvals in other selected countries worldwide (major territories) are listed in Table 1.1 .

Strabismus

The therapeutic use of BoNT/A began with Alan Scott, an ophthalmologist who was seeking a treatment for strabismus, a condition of ocular misalignment. Having read about the ability of BoNT/A to induce local changes in muscles through the inhibition of acetylcholine release, Scott believed it might be a useful nonsurgical treatment for strabismus. He hypothesized that BoNT/A would relax the injected extraocular muscles implicated in the deviation, enabling ocular realignment. In his initial study of 19 strabismus patients, Scott reported that BoNT/A dose-dependently improved eye position without causing weakness in adjacent muscles and without producing systemic effects. Scotts work, including a combination of double-blind and open-label studies conducted under an Investigational New Drug license, led to US Food and Drug Administration (FDA) approval of onabotulinumtoxinA (then Oculinum™) in 1989 for the treatment of strabismus.

Blepharospasm

Following the successful use of onabotulinumtoxinA in strabismus, Alan Scott postulated that it might also be useful for blepharospasm, a neurological disorder characterized by involuntary contraction of the eyelid muscles leading to repetitive and uncontrollable eyelid closure. Scott’s initial study showed improvement in all 39 injected patients. This was followed by double-blind studies, including those by our team at Columbia University, that confirmed the efficacy of onabotulinumtoxinA for blepharospasm. In 1989, onabotulinumtoxinA was approved by the FDA for the treatment of blepharospasm associated with dystonia in patients 12 years of age and older.