Introduction

The world of botulinum toxin has changed dramatically in the 30 years of our involvement. In 1982 the only available product was called ‘Oculinum’ and was available only from Alan Scott, MD, at the Smith-Kettlewell Institute for Visual Sciences in San Francisco. The dramatic concept of using ‘the most deadly poison’ to treat muscle disorders had, of course, already been published in Readers’ Digest and was soon to be published in the National Enquirer and other popular publications. At that time the indication for use was the treatment of strabismus although dystonia, especially blepharospasm, and hemifacial spasm were soon added to the list. Many other indications have since followed especially after the FDA’s first approval in the USA in 1989.

When discussing the future of this dramatic molecule it is hard to stay ahead of reality and common usage. We shall endeavor to tread the fine line between documenting what has been shown scientifically and wild speculation. However, the field is expanding so rapidly that this will be difficult.

One of the problems with discussing the clinical use of botulinum toxin is that the regulatory pathway and the rigorous scientific investigation of the efficacy and safety of new indications have consistently lagged behind off-label clinical use. We were using BoNT-A to treat glabellar lines more than 10 years before the regulatory studies began and 15 years before US FDA approval for glabellar lines. So it is not easy to keep track of the many areas where BoNT-A is being used and sort out those areas where its use is a major therapeutic advance. Some years ago we were in communication with a physician who was using aerosolized BoNT-A to treat asthma, but have heard nothing of this indication since. The same is true for the treatment of allergic rhinitis. By comparison, the use of BoNT-A to treat detrusor overactivity in individuals with paraplegia or other neurological problems appeared as an indication very early in the clinical development of BoNT-A. Urologists have subsequently gone on to use the toxin for overactive bladder in females and benign prostatic hypertrophy in males, and both of these indications should be approved by the FDA in the near future.

This short chapter will be speculative and opinionated. In addition, it may well be proven wrong! But we are close to the expanding body of knowledge about BoNT and hope that we shall be able to suggest at least some of the important areas of future knowledge and clinical use.

Newer indications

As the understanding of the mechanism of action of BoNT expands and as the number of clinicians exposed to the toxin increases, there have been great extensions in the clinical use of the toxin. For example, the use by physicians of the toxin for cosmetic purposes led to recognition that some of the treated individuals experienced improvement in headache and migraine. This led to a wider understanding of the mechanism of action of BoNT and subsequently use of the toxin to treat a range of conditions associated with pain. The recognition that BoNT treatment of hyperhidrosis would shrink sweat glands has led other physicians to treat other glands, thus improving benign prostatic hypertrophy and sialorrhea.

The range of conditions involving abnormal muscle function, pain, and excessive glandular function that is now being treated is extremely wide and is expected to expand further. Some of these are relatively specialized. The conditions that dermatologists recognize as being worsened by excessive sweating, such as benign familial pemphigus, can be improved by BoNT-A injection into the area. This is important, providing relief for those individuals but not being as important in sheer numerical terms as, for example headache and migraine.

Topical versus injectable

We had long presumed that the large size of the BoNT-A molecule would prevent it from passing through intact skin. That assumption has been proven incorrect and the effectiveness of topically applied BoNT-A has now been established (see Ch. 10). This will have important implications beyond the current clinical development both in axillary hyperhidrosis and in lateral orbital wrinkles and lines (crow’s feet). We would expect that the advantage of a needleless approach will encourage many more individuals to have excessive sweating treated, especially that of the palms and soles, face, and scalp. Also, those individuals who have normal levels of sweating but who choose not to sweat in these areas can be safely and effectively treated.