Botox and Dupuytren Disease?

Botox may have a use in the treatment of Dupuytren disease.

Right now, it's untested, but it has a scientific basis. Botox is not just the botulinium toxin. It's a biologic extract which contains a number of unique molecules. One of these is C3 transferase, an enzyme which blocks several steps in the pathway of fibrosis. Botox has been reported as a potential treatment for keloid scars and has been shown to reduce contracture, adhesions and fibrosis after experimental surgical wounds:

• Dendritic Fibroblasts in Three-dimensional Collagen Matrices 
• Novel Use of Botulinum Toxin to Ameliorate Arthrofibrosis: An Experimental Study in Rabbits 
• RAC Activity in Keloid Disease 
• Effect of Botulinum Toxin Type A on a Rat Surgical Wound Model 
• Innovative Therapies in the Treatment of Keloids and Hypertrophic Scars 
• The actin cytoskeleton in myofibroblast differentiation: Ultrastructure defining form and driving function

There is a large clinical experience to support the use of Botox in humans for treatment of benign disease.

C3 transferase based treatment of Dupuytren disease would be directed at prevention rather than correction. Current thought is that nodules, not cords, are the main location of biologic activity which results in contractures, and nodules are a logical starting study focus.

One type of study would be treatment of patients with nodules - and then following outcomes. The problem with this is that many people with only nodules may not develop contractures for decades:

• Eighteen years follow-up study of the clinical manifestations and progression of Dupuytren’s disease

Another option for study would be to add C3 transferase treatment as an adjunct to patients who are undergoing a procedure to correct Dupuytren contracture. The advantage of this would be that patients who are treated for contracture are likely to have recurrent contracture progression in a more predictable and shorter period of time than those who simply have nodules. This would shorten the needed study time and would give more statistical validity. Selection of patients with risk factors for early recurrence (positive family history, both hands involved, onset earlier than 50 years old, knuckle pads, Ledderhose and others) would similarly improve study analysis logistics. This approach has been applied to cortisone injection and perioperative Tamoxifen with encouraging results:

• Steroid Injection and Needle Aponeurotomy for Dupuytren Contracture:A Randomized, Controlled Study 
• Recurrence After Surgery For Dupuytren's Disease: A Randomised Controlled Trial With Double Blinding, Combining Segmental Fasciectomy With Placebo Or With Neo-Adjuvant Oral Tamoxifen

Interest in coordinating a Botox Dupuytren study may be directed to the Dupuytren Foundation: info@Dupuytrens.org

Charles Eaton MD

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