An Urgent Need

Proteins are large, exquisitely folded molecules that play essential and diverse roles in the human body. When normal protein folding is disrupted in progressive brain diseases, these misfolded proteins clump together – binding to form toxic aggregates.

Protein misfolding is a well-characterized hallmark of severe neurodegenerative diseases, including Alzheimer’s and Parkinson’s. Specifically, in Alzheimer’s disease, misfolded protein aggregates are plaques, made of aggregated b-amyloid, tangles, made of aggregated Tau, and sometimes a-synuclein aggregates that cause brain dysfunction and eventually, nerve cell death. In Parkinson’s Disease, a-synuclein aggregates are predominantly involved, sometimes accompanied by plaques, made of aggregated b-amyloid, and tangles, made of aggregated Tau.

Protein misfolding is also a characteristic of certain rare diseases caused by systemic accumulation of amyloid protein aggregates. Examples of systemic amyloidosis with accumulation of tissue-damaging aggregates in peripheral organs include several types of transthyretin (TTR) amyloidoses and light chain (AL) amyloidosis.

There is a critical unmet need to develop novel treatments for protein misfolding diseases, for which no approved disease-modifying treatments currently exist.

Alzheimer’s and Parkinson’s place an enormous economic and social burden on patients, caregivers, and society. Alzheimer’s is the most common neurodegenerative disease and the leading cause of dementia, which currently affects approximately 5.5 million in the US and 47 million worldwide. That number is expected to grow to 131 million by 2050.1, 2

Parkinson’s disease, the second most common neurodegenerative disease, affects an estimated 0.5 to 1 million in the US, and more than 10 million worldwide.3, 4

Systemic amyloidosis represents a broad collection of orphan misfolded protein diseases that can cause death through peripheral organ damage. Prominent among these diseases are transthyretin amyloidosis (ATTR), with the inherited versions of the disease affecting ~50,000 persons worldwide, and non-inherited ATTR affecting ~90% of persons >90 years old worldwide5, 6; and antibody light chain (AL) amyloidosis with up to 4,000 new cases per year in the US7. Both ATTR and AL amyloidosis are fatal diseases that should be treatable using protein aggregate reduction therapy, such as NPT189, to rescue organ function.

1. Alzheimer’s Association (www.alz.org)

2. Alzheimer’s Disease International, World Alzheimer report 2016, (www.alz.co.uk)

3. McGovern Institute for Brain Research at MIT (www.mcgovern.mit.edu)

4. Parkinson’s Disease Foundation (www.pdf.org)

5. Ando et al., Orphanet J Rare Dis, 2013

6. Ruberg et al., Circulation, 2012

7. Amyloidosis Research Consortium, Guidance for Industry – AL Amyloidosis – Developing Drugs for Treatment, Dec 2016 (www.arci.org)