Abstract
Approximately 1 in 2500 Americans suffer from Charcot-Marie-Tooth (CMT) disease. The underlying disease mechanisms are unique in most forms of CMT, with many point mutations on various genes causing a toxic accumulation of misfolded proteins. Symptoms of the disease often present within the first two decades of life, with CMT1A patients having reduced compound muscle and sensory action potentials, slow nerve conduction velocities, sensory loss, progressive distal weakness, foot and hand deformities, decreased reflexes, bilateral foot drop and about 5% become wheelchair bound. In contrast, the ultra-rare disease Giant Axonal Neuropathy (GAN) is frequently described as a recessively inherited condition that results in progressive nerve death. GAN usually appears in early childhood and progresses slowly as neuronal injury becomes more severe and leads to death in the second or third decade. There are currently no treatments for any of the forms of CMTs or GAN. We suggest that further clinical studies should analyse electrical impedance myography as an outcome measure for CMT. Further, additional quality of life (QoL) assessments for these CMTs are required, and we need to identify GAN biomarkers as well as develop new genetic testing panels for both diseases. We propose that using the Global Registry of Inherited Neuropathy (GRIN) could be useful for many of these studies. Patient advocacy groups and professional organizations (such as the Hereditary Neuropathy Foundation (HNF), Hannah's Hope Fund (HHF), The Neuropathy Association (TNA) and the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) can play a central role in educating clinicians and patients. Undertaking these studies will assist in the correct diagnosis of disease recruiting patients for clinical studies, and will ultimately improve the endpoints for clinical trials. By addressing obstacles that prevent industry investment in various forms of inherited neuropathies, we can envision treatment options for these rare diseases in the near future.
Highlights
There are currently no approved treatments for any of the forms of inherited neuropathy (IN), which are each considered rare diseases
Based on the prevalence of all CMTs being 1:2500 and the recent census figures of over 300 million people in the United States of America (USA), it is likely that more than 75,000 Americans have CMT1A, which is caused by the peripheral myelin protein 22 (PMP22) duplication gene phenotype, which represents 68.7% of all CMT Type 1s in the USA4
Assuming FDA and (IRB) approvals, a Phase I trial is expected to begin in the second quarter of 2014. With research reaching such advanced stages we propose that some efforts should be made to fill the various gaps in clinical studies, in order to translate therapeutics to patients more rapidly for the related diseases CMT1A, CMT2A and GAN
Summary
There are currently no approved treatments for any of the forms of inherited neuropathy (IN), which are each considered rare diseases. Since there is no clear delineation of disease progression symptoms, relationship to disease severity, longitudinal follow-up, determination of best methods of measuring QoL or disease-specific instrument, future studies should evaluate changes in impact of factors These factors should include improved medical care, education through the Internet, advocacy support from CMT organizations and other dynamics, on patients’ quality of life over the past ten years. Let pharmaceutical companies know the number of patients with a particular form of IN who would be willing to consider volunteering for experimental trials This longitudinal database of patient-contributed data includes the ability for patients to create an account that allows them to login and update information, complete questionnaires or provide patient-reported outcome measures and track results, compare their responses to the de-identified responses of other registry participants, and upload medical records for use in identifying confirmed diagnosis of hereditary neuropathy patients. A regular Hereditary Neuropathies Workshop could serve as a forum to promote awareness of IN, encourage patient recruitment for future clinical trials and GRIN, and provide a means for encouraging more participation by other researchers and companies in the field, as well as provide a learning platform to benefit new researchers; this would encourage the researchers’ development in this area and promote their interest in pursuing additional research projects in the field of hereditary neuropathies
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