Assistant Clinical Professor, Harvard Medical School,
Medical Director Associate Eye Physicians and Surgeons, Inc
Dr. Borodic has played a pivotal role in the development of botulinum toxin therapeutics (eg BOTOX, formerly OCCULINUM). He has developed assays to further understand the mechanisms which govern the safe administration via laboratory experimentation and clinical experience. His early work has been directed at understanding critical aspects of dosing which governs diffusion and control of this drug. Further work has revealed issues in formulation and preparation which influence the long term effectiveness of the treatment and the most effective administration techniques. He authored the first comprehension pharmacology chapter on the use of this drug (Chapter 10, Therapy with Botulinum Toxin, 1994 Mercel Decker – link). – PDF
Dr. Borodic directly worked with Dr. Ed Schantz and Dr. Johnson from the University of Wisconsin. Dr. Schantz initiated and championed the controlled production of the botulinum material used as a medicine. Dr. Alan Scott, an ophthalmologist was first to use injectable botulinum toxin as a therapeutic agent. Dr. Borodic also spent educational time at the Center for Disease Control learning about the science governing handling botulinum toxin.
Dr. Borodic’s therapeutic contributions involved mastering the scientific basis for injection strategies, describing the dose response relationships, planning concepts regarding controlled administration, uncovering initial defects in drug formulation, describing the immunity issues occurring with high dose applications, and describing the first cases treated with primary pain syndromes and headaches.
Dr. Borodic’s publications and patents have further motivated companies to produce new formulations of botulinum toxin which is currently under study and development.
(link to Curriculum vitae)
Dr. Borodic’s publications will go into much more detail on each of these points. (link to publications)
Botulinum toxin products (eg BOTOX and others) work by blocking neurotransmission. The unique pharmacology relates to two fundamental principles: 1. Regional effect which can be controlled by dose 2. Long duration of action 3. Multiple influences of blocked neurotransmission 4. Small mass dosing (because it’s toxin!) which allows for repeated dose without an immune appreciable response in most cases
The most obvious effect is weakening of muscles which produce a desirable effect on age dependent line and face wrinkles, modulation of involuntary muscular activity from cerebral palsy, dystopias, torticollis, blepharospasm, and hemifacial spasm. Additionally the drug has effect on non motor (non muscular) nerves which control body secretions, modulate certain inflammatory mediators (link), and may play a role in central nervous system processing.
Treatment of pain including migraine, sinus and tension headache is an example of extra muscular effects of the toxin.
Current issues governing drug selection relate to controlled administration, potency of dose, long term effectiveness, cost, duration of action, antigenicty of materials and selective effects.
Applications
The applications of botulinum toxin have been extensive. Originally the drug was used to treat crossed eyes (strabismus) and involuntary eyelid closure. From this prospective, changes on the muscular of the face associated with eyelid and peri-ocular injections led to the observation and application for the reduction of muscle tone generated wrinkles of the upper face. Further the effect on muscles being regional led to applications in involuntary movement and neck spasms (torticollis) as well as spasticity of the limbs (from strokes and cerebral palsy). Muscle based applications led to the discovery of a unique pain relieving property which has been used for the purpose of treating a number of headache and muscle pain disorders, including migraine, chronic tension headaches, TMJ disease, and certain type of neck pain.
– Botulinum toxin is thought to have a number of anti-inflammatory properties which have also been useful in regional inflammatory conditions.
– The drug has been used to treat certain forms of bowel spasms and internal spasms.
– Treatment of hyperactive sweating, salivary glands and other secretions have been treated with this drug.
The statement on the Safety of Botulinum Toxin products (Botox, Myobloc, Xeomin and Dysport).
Recently, the common press has published articles dealing with potential serious complications associated with the use of botulinum toxin, particularly Botox, for the treatment of certain diseases. It should be pointed out that these products have been used extensively by experienced physicians without significant risk for decades.
The center of the recent controversy has emerged from two observations. The first observation was made from a scientific study using botulinum toxin at high doses which revealed the toxin moved along nerves into the brain. This observation, however, was in doses that were far in excess of which are conventionally used for human treatment. To date, no long term neurotoxicity has ever been demonstrated using these agents. The mere fact that a drug can move into the brain does not mean that it is potentially damaging; for instance, antihistamines, sedatives and other type medications can penetrate the brain without any lasting or enduring side effects. To date there has been no neurologic side effects associated with the long term use of botulinum toxin. Dr. Borodic has served on safety committees, and as safety monitor for a number of clinical studies, and has used the medication for over 28 years. He has had no serious side effects in his practice with long term use of this medication.
The second category of sides effects associated with the use of botulinum toxin emerged from use of botulinum toxin for the treatment of cerebral palsy. In this area of very large dose applications, there can be substantial and serious side effects if the drug is used imprudently without regard to dosing limitations and injection placement. In certain rare cases, diffusion of the toxin at high doses leads to dangerous systemic weakness. One has to understand that the cosmetic and facial application of botulinum toxin as well as the applications in the human neck are in doses far less than those that had been advocated for children and some adults with spasticity and cerebral palsy that have suffered from substantial adverse effects from diffusion of the toxin. Some academic manuscripts had advocated doses far in excess of which should be used safely, particularly for children with cerebral palsy. Most recently this has led to a fine of the manufacturer of botulinum toxin, Allergan for over $600 million for off label promotion for this indication.
Patients in Dr. Borodic’s practice should be assured that this dose will not be used in any such patients and this has not been a problem at Associated Eye Physicians and Surgeons, Inc. in its 30+ year history.