In a recent press release, genome editing company Intellia Therapeutics, Inc. (“Intellia”) announced its recent MHRA authorization to begin a Phase 1 clinical trial to evaluate its therapeutic candidate NTLA-2001. The investigational therapy is designed to treat patients with hereditary transthyretin amyloidosis (hATTR) with polyneuropathy.

NTLA-2001

Intellia uses its proprietary non-viral lipid nanoparticle platform to develop in vivo therapies. In vivo means that the therapy is administered directly to the patient. Now, NTLA-2001 is Intellia’s lead therapeutic candidate. By administering it directly to a patient intravenously, Intellia hopes that NTLA-2001 will lower TTR levels for years, if not for life, after just one dose.

Within the Phase 1 clinical trial, which Intellia hopes to begin before 2020 is over, 38 patients will receive NTLA-2001. Overall, the trial will seek to evaluate the safety, efficacy, pharmacokinetics, pharmacodynamics, and tolerability of NTLA-2001.

Hereditary ATTR Amyloidosis (hATTR)

Overall, there are six main types of amyloidosis, a condition in which abnormal amyloid proteins accumulate in organs like the heart and kidneys. As these proteins build up, the organs become stiff and lose function. The subtypes of amyloidosis are primary, secondary, familial, dialysis-related, senile systemic, and organ-specific. For the purpose of this article, we will discuss hereditary ATTR amyloidosis (hATTR), which is the familial form of the condition. This genetic disease impacts the heart and nervous system. Because of TTR gene mutations, transthyretin misfolds and accumulates throughout the organs.

Even with hATTR, there are subcategories: familial amyloid cardiomyopathy (FAC), senile systemic amyloidosis, and familial amyloid polyneuropathy (FAP). The Intellia trial will explore NTLA-2001 as a treatment for patients with the latter form. Symptoms vary based on affected organ:

• Kidneys
  • Excess protein in the urine
  • Renal failure
  • Lung, leg, abdominal, and arm swelling
• Nervous system
  • Nerve damage
  • Dizziness and fainting
  • Changes in eye movement control
  • Nausea and vomiting
  • Muscle pain and weakness
• Heart
  • Nausea and vomiting
  • Unintended weight loss
  • Chest pain
  • Heart palpitations
  • Swelling of the lower extremities
  • Fatigue
  • Insomnia
  • Shortness of breath
• Digestive System
  • Nausea
  • Diarrhea or constipation
  • Changes in bladder control
  • Appetite loss
  • Unintended weight loss

Learn more about hATTR.