The laboratories of Rudolf Martini and Richard Stanley have previously reported the discovery of a novel biological pathway in the human immune system, which is turned on in response to injury in the peripheral nervous system. A biological messenger that is produced by this pathway following nerve injury has also been identified and shown to accelerate the peripheral nerve damage that occurs in an animal model of CMT1X. These investigators have been joined by the laboratory of Jonathan Lai in a TIN-sponsored collaborative effort to design a new therapy that blocks this disease-amplifying factor. The goal of this new approach is to identify a novel antibody therapy that can stop and even reverse the nerve damage that occurs in patients with heritable neuropathies such as CMT1X.
Efforts by the team to isolate the biological messenger were successful. This then allowed the team to create libraries of antibodies that might recognize this disease-amplifying factor. In sorting through this antibody collection, the team has now met a key success criterion of identifying antibodies that both recognize and neutralize the disease factor. Several of the best antibodies that were identified are presently being further engineered to optimize their potency even further than has already been observed.
The next step will be to proceed to testing in animals, in order to demonstrate that these antibodies can remove the human disease factor circulating in the blood of a CMT1X mouse. To support this testing, a mouse model that expresses both the human version of the factor, and the disease form of the CMT1X gene, was created by the Martini laboratory. This novel mouse model has been shown to replicate the progressive, peripheral nerve damage that is seen in CMT1X patients. Antibodies that can neutralize the disease factor in these mice will then be tested to confirm that they can stop or even reverse symptoms of CMT1X.
This is a very exciting approach that takes advantage of biopharmaceutical engineering technologies that are currently responsible for 30% or more of drugs annually approved by the US FDA.