You can read about existing treatment options for ATTR amyloidosis here. Below you will find some information on new areas of research that may help people with ATTR amyloidosis in the future.
Treatments
You can read about existing treatment options for ATTR amyloidosis here. Below you will find some information on new areas of research that may help people with ATTR amyloidosis in the future.
Clinical research
In recent years effective new drugs for ATTR amyloidosis have become available. These drugs can improve symptoms and delay disease progression in suitable patients. Several other drugs are in various stages of development, offering yet more hope for the future. The trials discussed below are ongoing at the London National Amyloidosis Centre. For more details on each trial, see clinicaltrials.gov.
Clinical research
In recent years effective new drugs for ATTR amyloidosis have become available. These drugs can improve symptoms and delay disease progression in suitable patients. Several other drugs are in various stages of development, offering yet more hope for the future. The trials discussed below are ongoing at the London National Amyloidosis Centre. For more details on each trial, see clinicaltrials.gov.
Genetic based therapies
In 2019, regulatory authorities in the UK and the US approved patisiran (a small interfering RNA drug) and inotersen (an antisense oligonucleotide drug) for treating neuropathy caused by hereditary ATTR amyloidosis. You can read more about patisiran and inotersen here.
The early trials only assessed the impact of these drugs on nerve damage caused by ATTR amyloidosis. Effects on cardiac ATTR amyloidosis (also known as cardiomyopathy) were not formally evaluated and patients with wild-type ATTR amyloidosis were not included in the drug trials.
Some of the ongoing clinical trials of patisiran, and of other, newer genetic therapies include patients with both hereditary and wild-type cardiac ATTR amyloidosis.
A small study called Patisiran in Patients With Hereditary Transthyretin-mediated Amyloidosis (hATTR Amyloidosis) Disease Progression Post-Liver Transplant is evaluating patisiran in a patient group who were not included in the early trials.
Vutrisiran is a second-generation RNA inhibitor– similar to patisiran – that is administered by injection under the skin (as opposed to via intravenous infusion).
The HELIOS-B study is comparing vutrisiran with placebo in patients with ATTR amyloidosis (hereditary or wild type) with cardiomyopathy.
AKCEA-TTR-LRx is a second-generation RNA inhibitor, belonging to the antisense oligonucleotide drug class. The NEURO-TTRansform study is comparing AKCEA-TTR-LRx to inotersen in patients with hereditary ATTR amyloidosis polyneuropathy. The CARDIO-TTRansform trial is evaluating the efficacy and safety of AKCEA-TTR-LRx in patients with ATTR cardiomyopathy (hereditary or wild type).
Genetic based therapies
In 2019, regulatory authorities in the UK and the US approved patisiran (a small interfering RNA drug) and inotersen (an antisense oligonucleotide drug) for treating neuropathy caused by hereditary ATTR amyloidosis. You can read more about patisiran and inotersen here.
The early trials only assessed the impact of these drugs on nerve damage caused by ATTR amyloidosis. Effects on cardiac ATTR amyloidosis (also known as cardiomyopathy) were not formally evaluated and patients with wild-type ATTR amyloidosis were not included in the drug trials.
Some of the ongoing clinical trials of patisiran, and of other, newer genetic therapies include patients with both hereditary and wild-type cardiac ATTR amyloidosis.
A small study called Patisiran in Patients With Hereditary Transthyretin-mediated Amyloidosis (hATTR Amyloidosis) Disease Progression Post-Liver Transplant is evaluating patisiran in a patient group who were not included in the early trials.
Vutrisiran is a second-generation RNA inhibitor– similar to patisiran – that is administered by injection under the skin (as opposed to via intravenous infusion).
The HELIOS-B study is comparing vutrisiran with placebo in patients with ATTR amyloidosis (hereditary or wild type) with cardiomyopathy.
AKCEA-TTR-LRx is a second-generation RNA inhibitor, belonging to the antisense oligonucleotide drug class. The NEURO-TTRansform study is comparing AKCEA-TTR-LRx to inotersen in patients with hereditary ATTR amyloidosis polyneuropathy. The CARDIO-TTRansform trial is evaluating the efficacy and safety of AKCEA-TTR-LRx in patients with ATTR cardiomyopathy (hereditary or wild type).
TTR stabilizer
Destabilization, misfolding and aggregation of TTR leads to amyloid deposits.
Several small molecules have been shown to bind to and stabilize TTR protein, potentially preventing a key part of the pathway that produces amyloid.
AG10 is a TTR stabilizer drug being developed to treat ATTR amyloidosis. It is hoped that AG10 will halt or slow ATTR disease progression. The Eidos AG10-301 study is evaluating the efficacy and safety of AG-10 in patients with symptomatic ATTR amyloidosis cardiomyopathy (hereditary and wild type).
TTR stabilizer
Destabilization, misfolding and aggregation of TTR leads to amyloid deposits.
Several small molecules have been shown to bind to and stabilize TTR protein, potentially preventing a key part of the pathway that produces amyloid.
AG10 is a TTR stabilizer drug being developed to treat ATTR amyloidosis. It is hoped that AG10 will halt or slow ATTR disease progression. The Eidos AG10-301 study is evaluating the efficacy and safety of AG-10 in patients with symptomatic ATTR amyloidosis cardiomyopathy (hereditary and wild type).
CRISPR/cas9 gene editing therapy
CRISPR/cas9 technology is a novel gene editing tool that allows scientists to alter genes very precisely and efficiently. Using this technique, specific sections of the DNA can be removed, altered or added – such as the abnormal protein that causes hATTR amyloidosis.
NTLA-2001 is an experimental therapy that could potentially be the first curative treatment for hATTR amyloidosis.
NTLA-2001 uses a lipid nanoparticle delivery system to deliver the gene editing CRISPR protein to the liver. The goal is to permanently delete the gene for TTR in a single course of treatment.
Preclinical data has shown promising results. The Phase 1 clinical trial, led by researchers at the UCL National Amyloidosis Centre at the Royal Free London Hospital has found strong interim results from the first six patients in the trial. Production of the harmless protein was reduced by 96% by day 28 following treatment, with no serious adverse events observed. This is the first-time the therapy has been administered to humans.
CRISPR/cas9 gene editing therapy
CRISPR/cas9 technology is a novel gene editing tool that allows scientists to alter genes very precisely and efficiently. Using this technique, specific sections of the DNA can be removed, altered or added – such as the abnormal protein that causes hATTR amyloidosis.
NTLA-2001 is an experimental therapy that could potentially be the first curative treatment for hATTR amyloidosis.
NTLA-2001 uses a lipid nanoparticle delivery system to deliver the gene editing CRISPR protein to the liver. The goal is to permanently delete the gene for TTR in a single course of treatment.
Preclinical data has shown promising results. The Phase 1 clinical trial, led by researchers at the UCL National Amyloidosis Centre at the Royal Free London Hospital has found strong interim results from the first six patients in the trial. Production of the harmless protein was reduced by 96% by day 28 following treatment, with no serious adverse events observed. This is the first-time the therapy has been administered to humans.
Clinical trials at the National Amyloidosis Centre
The NAC can now offer patients with ATTR amyloidosis, subject to various eligibility criteria demanded by the pharmaceutical companies, various opportunities for treatment with the new drugs or for participation in clinical trials. For details of ongoing trials at the NAC see here.
Clinical trials at the National Amyloidosis Centre
The NAC can now offer patients with ATTR amyloidosis, subject to various eligibility criteria demanded by the pharmaceutical companies, various opportunities for treatment with the new drugs or for participation in clinical trials. For details of ongoing trials at the NAC see here.