Transthyretin amyloid cardiomyopathy belongs to the group of systemic amyloidoses. The cause of the disease is the incorporation of abnormally folded transthyretin (TTR), an amyloid protein, into the heart muscle tissue, which is due to gene mutations. The disease is inherited in an autosomal dominant manner.
In adulthood, there is a restrictive cardiomyopathy with heart failure as well as bradyarrythmias. Sensorimotor polyneuropathy in the form of a familial amyloid polyneuropathy is also a possibility. The prognosis depends on the severity of the heart failure. Sudden cardiac death due to arrhythmias also plays a role. The 5-year survival rate is less than 50%.
The research goal around ATTR-CM is to treat the causal problem - namely ATTR deposition in the heart muscle tissue. Previous therapy options were able to slow down the progression of the disease, but not the reduction of the deposits.
The anti-ATTR antibody investigated in the present phase I study, on the other hand, was developed precisely for this purpose. It removes the abnormally folded TTR from the cardiomyocytes by phagocytosis.
The double-blind randomised study proved that the antibody (so far referred to as NI006) could achieve a reduction of the amyloid load in the heart muscle tissue within 12 months, if it was infused in a concentration of at least 10 mg per kilogram of body weight.
There were no serious adverse effects. Overall, the pharmacological profile of the new substance corresponds to that of an IgG antibody.
The new anti-TTR antibody gives hope for a causal treatment of ATTR-CM, a disease that has so far been fatal in most cases. Further studies are much needed, but the data of this latest phase I study are promising.