April 2, 2020

Arkuda to Present Update on its First-in-Class Small Molecules for the Treatment of GRN-Related Frontotemporal Dementia at the 2020 AAT-AD/PD Virtual Meeting

Watertown, MA – April, 2, 2020 – Arkuda Therapeutics, a company leveraging new insights into progranulin and lysosomal biology to develop medicines to change the trajectory of neurodegenerative disease, will present data at the virtual meeting of Advances in Alzheimer’s and Parkinson’s Therapies (AAT-AD/PD™) April 2-5, demonstrating the company’s compounds successfully increase levels of both progranulin (PGRN) and granulins in preclinical models of progranulin-related frontotemporal dementia (FTD-GRN) and improve lysosomal function (Abstract #572). Lower granulin concentration in lysosomes and the ensuing lysosomal dysfunction have been linked to the development and progression of a range of neurodegenerative diseases including FTD-GRN, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and Alzheimer’s disease.

“This is important evidence that Arkuda’s compounds are biologically active and achieve the desired effect of increasing levels of secreted PGRN as well as lysosomal granulins. By increasing both, we hope to restore lysosomal health, normalize immunomodulation, and prevent progressive neuronal death,” said Gerhard Koenig, PhD, Co-Founder, President and CEO of Arkuda Therapeutics.

PGRN is a protein known to play a key role in lysosomal function and innate immunity in the brain. The protein is mainly targeted to lysosomes, where it is processed into its biologically active subunits, granulins, which are critical for maintaining normal lysosomal function.

Arkuda scientists conducted a small molecule screen in BV-2 cells and subsequent structural optimization to identify potent, novel molecules to increase progranulin secretion and lysosomal granulins. These compounds increase PGRN secretion and lysosomal granulins in multiple relevant cell lines, including iPSC-derived neurons from FTD-GRN patients. In contrast, a monoclonal antibody blocking sortilin, the key cell surface PGRN receptor, reduced granulins in neurons.

Additionally, Arkuda molecules improved lysosomal function in PGRN deficient cells, as measured by a reduction in lipid droplet accumulation, a hallmark of lysosomal dysfunction, while also modulating a key pro-inflammatory cytokine.

“We are very excited about the dual effect of our compounds to increase both extracellular PGRN and lysosomal granulins, as well as the evidence of positive functional benefit with regards to lysosomal function and immunomodulation, and look forward to advancing our lead program toward clinical development,” said Dr. Koenig.


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About Arkuda Therapeutics
Arkuda Therapeutics is a biotechnology company leveraging new insights into progranulin and lysosomal biology to develop medicines to change the trajectory of neurodegenerative disease. Arkuda’s lead compounds aim to correct progranulin deficiency and lysosomal dysfunction in GRN-related frontotemporal dementia (FTD-GRN), a genetically-defined subtype of frontotemporal dementia caused by an autosomal dominant mutation in the GRN gene. Arkuda launched in November 2019 with $44 million from leading life science investors including Atlas Venture, Pfizer Ventures, funds managed by Tekla Capital Management LLC, and Mission BioCapital. To learn more visit


Media Contact:
Lissette Steele
Verge Scientific Communications









Lissette Steele
Verge Scientific Communications