Patent Picks: Scleroderma Treatments

Limited scleroderma is a chronic autoimmune disease characterized by hardening of the hand’s skin and vasculature. The disease is rare—only about 77,000 Americans have it—and it afflicts women three times as often as is does men. The exact cause of these painful cutaneous manifestations is not known, but viruses and oxidative stress are possible suspects. The disease first presents itself as a dysfunction in the lining of the hand’s blood vessels resulting in inflammation, collagen deposition, and impairment in the ability to create new blood vessels. There is no cure for scleroderma, only treatments to relieve symptoms, such as pain from ulceration and stiffness due to vasoconstriction. Here, we highlight three advances in scleroderma treatment from the databases of Chemical Abstracts Service (CAS).

Researchers at Cytori Therapeutics use a patient’s own adipose, or fat, cells to treat some of the worse symptoms of the disease (WO 2015042182). The process involves using a liposuction device to remove fat from the patient, an amount roughly equal to a volume of half-a-can of soda, says John Fraser, the chief scientist at Cytori. With a proprietary enzymatic digestion, Cytori’s system can remove fat cells from the sample, leaving other adipose cell types that can contribute to healing, such as stem cells, mesenchymal and endothelial progenitor cells, lymphatic cells, and pericytes. Clinicians can then inject these fat-free adipose cells at the site of a patient’s scleroderma lesions. The injected cells stimulate production of factors that promote blood vessel growth, such as VEGF and PIGF. In a pilot study, researchers tested the therapy on 12 scleroderma patients who had functional disability in their hands. One year after treatment, the patients regained significant function in their hands and had significantly less pain, Fraser tells C&EN.

Tyrosine kinases are responsible for the activation of multitudes of signaling pathways in cells, including those that initiate inflammation and eventual hardening of the hand’s skin and vasculature in scleroderma patients. A team from PreCision Dermatology formulated a cream that incorporates a tyrosine kinase inhibitor (TKI) as a topical treatment for scleroderma (WO 2015005985). The cream consists of imatinib mesylate, a TKI approved by FDA to treat chronic myeloid leukemia, dissolved in a mixture of phosphate-buffered saline, benzyl alcohol, ethanol, and hydroxypropyl cellulose. When given to mice with scleroderma, the TKI cream decreased inflammation and kinase receptor gene expression. In 2014, PreCision was bought by Valeant Pharmaceuticals for $450 million.

People who suffer from scleroderma often experience pain caused by the constriction of blood vessels in their hands. Dan Berkowitz and Gautam Sikka from Johns Hopkins University may have a way to relieve that pain through a light-based treatment. The method takes advantage of a little known phenomenon in which blood vessels relax when stimulated with blue light. The mechanism behind the relaxation is thought to involve melanopsin receptors, which play an important role in regulating the body’s circadian rhythms. The protein probably resides in the smooth muscle layer of blood vessels, Berkowitz says. However, blood vessels become desensitized from chronic light exposure. Berkowitz says that he and Sikka next want to identify melanopsin receptor kinase inhibitors to pair with the photorelaxation therapy to block the desensitization effect. So far the team has studied the phenomenon only in isolated blood vessels and in the tail arteries of live mice but plans to test in animal models of scleroderma.