This mutation produced a frameshift mutation, which led to a stop codon at position 131. SOD1 activity was decreased by about 30%. The patient’s histological examination showed severe reduction in lower motor neurons. Upon further study, this case proved to be important because it demonstrated that SOD1 mutations might not effect steady neuropathological changes, and that environmental and genetic factors might affect the phenotype of the SOD1 mutations. Treatment
PBP is aggressive and relentless, and there were no treatments for the disease as of 2005. However, early detection of PBP is the optimal scenario in which doctors can map out a plan for management of the disease. This typically involves symptomatic treatments that are frequently used in many lower motor disorders. History
The disease was first recognized by the French neurologist Guillaume Duchenne in 1860 and termed, “labioglossolaryngeal paralysis”. In 1859, Wachsmuth changed the name to progressive bulbar palsy. In 1869, Charcot studied the involvement of the corticospinal tracts and with Joffroy, who noted the loss of the bulbar motor nuclei, discovered the similarities to amyotrophic lateral sclerosis (ALS). It was observed that a distinction from ALS was fatigue that predominated in muscles innervated by lower cranial nerve nuclei, rather than the upper motor neurons. See also
Amyotrophic lateral sclerosis
Motor neuron disease

References
Bibliography
Lapiedra RC, Moreno Lopez LA, and Esparza Gomez GC. Progressive bulbar palsy: a case report diagnosed by lingual symptoms. J Oral Pathol Med. 31: 277-279. (2002)
Hughes TAT and Wiles CM. Neurogenic dysphagia: the role of the neurologist. J Neurol Neurosurg Psychiatry. 64:569-572.
Co-administration with ketoconazole, a strong CYP3A4 inhibitor, results in a 22% increase in the AUC, and potentially an increase in the rate of adverse effects experiencedSince bedaquiline can also prolong the QT interval, use of other QT prolonging drugs should be avoided. Other medications for tuberculosis that can prolong the QT interval include fluoroquinolones and clofazimine. Mechanism of action
Bedaquiline blocks the proton pump for ATP synthase of mycobacteria. It is the first member of a new class of drugs called the diarylquinolines. Bedaquiline is bactericidal. ATP production is required for cellular energy production and its loss leads inhibition of mycobacterial growth within hours of the addition of bedaquiline. The onset of bedaquiline-induced mycobacterial cell death does not occur until several days after treatment, but nonetheless kills consistently thereafter. Resistance
The specific part of ATP synthase affected by bedaquiline is subunit c which is encoded by the gene atpE. Mutations in atpE can lead to resistance. Mutations in drug efflux pumps have also been linked to resistance. Ongoing research
In vitro experiments have indicated that Bedaquiline may also target the mitochondrial ATP synthase of malignant mammalian cells and reduce the rate of metastasis. History
Bedaquiline was described for the first time in 2004 at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting, after the drug had been in development for over seven years.