Another Drug For TTR Amyloidosis

Why should those of us interested in engineered longevity pay attention to research and drug development for a type of amyloidosis called TTR amyloid polyneuropathy (ATTR-PN) or Familial Amyloid Polyneuropathy (FAP), a condition that likely has only around 10,000 sufferers worldwide? The answer is that forms of TTR amyloidosis have a much broader relevance to degeneration and death in the oldest old, those centenarians who have survived or avoided all other forms of age-related disease. The "TTR" in the condition name refers to transthyretin, a protein that becomes misfolded and forms deposits outside cells that then cause all sorts of issues:

Coles argues [that supercentenarians] aren't perishing from the typical scourges of old age, such as cancer, heart disease, stroke, and Alzheimer's Disease. What kills most of them, he says, is a condition, extremely rare among younger people, called senile cardiac TTR Amyloidosis. TTR is a protein that cradles the thyroid hormone thyroxine and whisks it around the body. In TTR Amyloidosis, the protein amasses in and clogs blood vessels, forcing the heart to work harder and eventually fail. "The same thing that happens in the pipes of an old house happens in your blood vessels," says Coles.

Earlier this year, I pointed out one research group working on a way to treat this class of conditions:

Prof Pepys was working then in collaboration with Roche. But the Swiss pharmaceutical giant eventually pulled out. "While we had promising early results [with CPHPC] they were not enough to benefit patients with advanced disease," he says. "Something more dramatic is needed."

That something turns out to a combination of CPHPC with an antibody - a molecular guidance system designed to seek out amyloid deposits in vital organs. Now Prof Pepys has reached an agreement with another big pharmaceutical group, UK-based GlaxoSmithKline, to collaborate on producing a treatment for amyloidosis based on the CPHPC-antibody combination.

My attention was recently directed to FoldRx, a company currently trialing another drug aimed at interfering in the process by which TTR amyloids form. Their intent is treatment of Familial Amyloid Polyneuropathy:

The drug [tafamidis] stabilizes wild-type and variant TTR, prevents misfolding of the protein by preventing tetramer dissociation and inhibits the formation of TTR amyloid fibrils. ... No disease progression was observed in 60% of tafamidis patients as compared to 38% of placebo patients after 18 months treatment. In addition, there was a significant deterioration in [quality of life] in placebo patients compared to those treated with tafamidis after 18 months.

Small steps forward. Clinical trials and multiple groups working on the underlying science are a good sign for future progress in clearing up varying forms of amyloidosis, even if present results offer only incremental improvement.