Patisiran

What is Patisiran?

Patisiran is an advanced medication used in the treatment of a rare and serious genetic condition known as hereditary transthyretin-mediated (hATTR) amyloidosis. Marketed under the brand name Onpattro, Patisiran is classified as an RNA interference (RNAi) therapeutic. It represents a significant breakthrough in targeted therapy, designed to address the root cause of the disease by reducing the production of abnormal proteins.

Hereditary ATTR amyloidosis is characterized by the accumulation of misfolded transthyretin (TTR) protein in various organs and tissues throughout the body, leading to progressive damage and dysfunction. Patisiran offers a novel approach by interfering with the genetic instructions for producing this problematic protein, thereby preventing its formation and subsequent deposition.

How Does it Work?

The mechanism of action for Patisiran is rooted in RNA interference (RNAi), a natural biological process that regulates gene expression. Patisiran is a small interfering RNA (siRNA) encapsulated within a lipid nanoparticle. Once administered, these nanoparticles deliver the siRNA specifically to liver cells, which are the primary site of TTR protein production.

Inside the liver cells, the siRNA in Patisiran binds to the messenger RNA (mRNA) that carries the genetic code for producing both variant and wild-type TTR protein. This binding triggers the degradation of the TTR mRNA, effectively silencing the gene responsible for its production. By reducing the amount of TTR mRNA available, Patisiran significantly lowers the synthesis of TTR protein. This reduction in TTR protein levels helps to decrease the formation and deposition of amyloid fibrils in tissues, thereby halting or slowing the progression of hATTR amyloidosis and its associated symptoms, particularly neurological manifestations like polyneuropathy.

Medical Uses

Patisiran is specifically indicated for the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. This condition is caused by mutations in the TTR gene, leading to the production of unstable TTR protein that misfolds and aggregates into amyloid fibrils. These amyloid deposits can accumulate in nerves, heart, gastrointestinal tract, kidneys, and eyes, causing a wide range of debilitating symptoms.

The primary use of Patisiran is to manage the polyneuropathy associated with hATTR amyloidosis. Polyneuropathy refers to damage to multiple peripheral nerves, which can result in symptoms such as numbness, tingling, pain, weakness, and autonomic dysfunction affecting digestion, blood pressure, and bladder control. By reducing the circulating levels of TTR protein, Patisiran aims to prevent further nerve damage and potentially improve neurological function, thereby enhancing the quality of life for patients living with this progressive disease.

Dosage

Patisiran is administered intravenously by a healthcare professional. The recommended dose is 0.3 mg/kg of body weight, given once every three weeks. It is crucial that patients receive pre-medication before each infusion to reduce the risk of infusion-related reactions. This pre-medication typically includes a corticosteroid, an H1 blocker (antihistamine), and an H2 blocker, and may also include paracetamol (acetaminophen).

The infusion itself is administered slowly over approximately 80 minutes. Patients are monitored during and after the infusion for any signs of adverse reactions. The treatment duration with Patisiran is ongoing, as it is a chronic condition that requires continuous management to suppress TTR protein production and prevent disease progression. Adherence to the prescribed dosage and pre-medication regimen is vital for the safety and efficacy of the treatment.

Side Effects

Like all medications, Patisiran can cause side effects, though not everyone experiences them. The most common side effects are often related to the infusion process and include infusion-related reactions. These can manifest as flushing, back pain, nausea, abdominal pain, shortness of breath, headache, dizziness, and chest tightness. Pre-medication is given to help mitigate these reactions.

Other common side effects reported with Patisiran include peripheral edema (swelling, particularly in the legs and feet), diarrhea, nausea, vomiting, abdominal pain, dyspnea (shortness of breath), muscle spasms, and arthralgia (joint pain). Some patients may also experience decreased vitamin A levels, as TTR protein is involved in vitamin A transport. Regular monitoring of vitamin A levels and supplementation may be necessary. Patients should report any new or worsening symptoms to their doctor promptly.

Drug Interactions

Due to its specific mechanism of action as an RNA interference therapeutic, Patisiran is not extensively metabolized by the cytochrome P450 enzyme system, which is commonly involved in drug interactions. Therefore, significant drug-drug interactions through this pathway are not typically expected.

However, caution should still be exercised when Patisiran is administered concurrently with other medications, especially those that might exacerbate certain side effects, such as fluid retention or gastrointestinal issues. For example, drugs that can contribute to peripheral edema might theoretically increase the severity of this side effect. Patients should always inform their healthcare provider about all medications they are taking, including prescription drugs, over-the-counter medicines, and herbal supplements, to ensure comprehensive safety evaluation and management.

FAQ

What is hereditary transthyretin-mediated (hATTR) amyloidosis?

Hereditary ATTR amyloidosis is a rare, progressive genetic disease caused by mutations in the TTR gene, leading to the production of abnormal transthyretin protein. This protein misfolds and accumulates as amyloid deposits in various organs, causing damage and dysfunction.

How is Patisiran administered?

Patisiran is administered as an intravenous infusion by a healthcare professional. It is given once every three weeks, with pre-medication required before each infusion to reduce the risk of infusion-related reactions.

How long does Patisiran treatment last?

Patisiran treatment is typically ongoing. As hATTR amyloidosis is a chronic condition, continuous therapy is usually necessary to maintain suppression of TTR protein production and manage disease progression.

What are infusion-related reactions?

Infusion-related reactions are a common side effect of intravenous medications like Patisiran. Symptoms can include flushing, headache, nausea, back pain, or shortness of breath. Pre-medication is given to help minimize these reactions.

Is Patisiran a cure for hATTR amyloidosis?

Patisiran is not a cure for hATTR amyloidosis, but it is a highly effective treatment that targets the underlying cause of the disease. It aims to halt or slow disease progression, improve neurological function, and enhance the quality of life for patients.

Products containing Patisiran are available through trusted online pharmacies. You can browse Patisiran-based medications at ShipperVIP or Medicenter.

Summary

Patisiran, known commercially as Onpattro, represents a groundbreaking therapeutic option for adults suffering from hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy. Through its innovative RNA interference (RNAi) mechanism, Patisiran specifically targets and reduces the production of the misfolded transthyretin (TTR) protein in the liver, which is the root cause of the disease. By lowering TTR levels, it helps prevent further amyloid deposition and nerve damage, offering significant relief and improved quality of life for patients.

While requiring regular intravenous administration and pre-medication to manage potential infusion-related reactions, Patisiran has demonstrated a profound impact on managing this debilitating condition. Its targeted approach underscores the advancements in modern medicine, providing hope and a more stable future for individuals affected by hATTR amyloidosis.