Our therapeutic areas

Our therapeutic areas

Hereditary transthyretin amyloidosis (hATTR)

hATTR is a rare, progressive, and fatal disease caused by the buildup of misfolded transthyretin (TTR) protein.1 TTR is synthesised primarily by the liver. The protein name is related to its function in transporting the thyroid hormone thyroxine and retinol (vitamin A).2

hATTR is a genetic disorder with autosomal dominant inheritance, resulting from a mutation in the TTR gene. TTR amyloid deposits aggregate in the nervous system, heart, kidneys and other organs.3

hATTR can present as4:

-       Progressive sensory, autonomic, and motor polyneuropathy

-       An infiltrative type of cardiomyopathy

-       A mixed phenotype of the above

The burden of disease is high in patients with hATTR and worsens as the disease progresses, leading to death within approximately 10 years of symptom onset.4

Familial chylomicronaemia syndrome (FCS)

FCS is an ultra-rare genetic disease characterised by extremely high levels of plasma triglycerides (10 to 100 times normal values) and a buildup of lipoprotein particles called chylomicrons.5,6 Patients with FCS have inherited mutations that reduce the activity of lipoprotein lipase, an enzyme that breaks down triglycerides and chylomicrons.5 This results in severe hypertriglyceridaemia, the hallmark feature of the disease, which places the patient at an increased risk of acute, potentially fatal pancreatitis.7 Recurrent episodes of acute pancreatitis may result in long-term complications including chronic pancreatitis and diabetes. FCS is also associated with a breadth of cognitive impairments, significant emotional burden, and poor mental health.6,8

The standard of care for patients with FCS is strict dietary control in which fat intake is restricted to <15 to 20g/day. Even short term ingestion of fat can result in highly exaggerated triglycerides that place patients at risk for acute pancreatitis. 6

References:  1. Stewart M, Shaffer S, Murphy B, et al. Characterizing the high disease burden of transthyretin amyloidosis for patients and caregivers. Neurol Ther. 2018;7(2):349-364. doi:10.1007/s40120-018-0106-z.  2. Ueda M, Ando Y. Recent advances in transthyretin amyloidosis therapy. Transl Neurodegener. 2014;3:19. doi:10.1186/2047-9158-3-19.  3. Conceição I, González-Duarte A, Obici L, et al. “Red-flag” symptom clusters in transthyretin familial amyloid polyneuropathy. J Peripher Nerv Syst. 2016;21(1):5-9. doi:10.1111/jns.12153.  4. Ando Y, Coelho T, Berk JL, et al. Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orphanet J Rare Dis. 2013;8:31. doi:10.1186/1750-1172-8-31.  5. Stroes E, Moulin P, Parhofer KG, Rebours V, Löhr J-M, Averna M. Diagnostic algorithm for familial chylomicronemia syndrome. Atheroscler Suppl. 2017;23:1-7. doi:10.1016/j.atherosclerosissup.2016.10.002.  6. Williams L, Rhodes KS, Karmally W, Welstead LA, Alexander L, Sutton L; for patients and families living with FCS. Familial chylomicronemia syndrome: bringing to life dietary recommendations throughout the life span. J Clin Lipidol. 2018;12(4):908-919. doi:10.1016/j.jacl.2018.04.010.  7. Gaudet D, de Wal J, Tremblay K, et al. Review of the clinical development of alipogene tiparvovec gene therapy for lipoprotein lipase deficiency. Atheroscler Suppl. 2010;11(1):55-60. doi:10.1016/j.atherosclerosissup.2010.03.004.  8. Davidson M, Stevenson M, Hsieh A, et al. The burden of familial chylomicronemia syndrome: results from the global IN-FOCUS study. J Clin Lipidol. 2018;12(4):898-907.e2. doi:10.1016/j.jacl.2018.04.009.