Jaya Biosciences Presents Updated Preclinical Data in Alzheimer’s Disease at the 45th SIMD Annual Meeting
- Study results confirm potential utility of targeting lysosomal genes to treat neurodegenerative diseases, including Alzheimer’s disease -
South San Francisco, CA, April 16, 2024 – Jaya Biosciences, Inc. (“JayaBio” or “the Company”), a privately held early-stage life-sciences company developing CNS-directed gene therapies for unmet needs in the neurodegenerative diseases, reported preclinical data at the 45th Annual Meeting of the Society for Inherited Metabolic Disorders (SIMD), a leading research conference on inherited metabolic diseases, including lysosomal diseases.
During a podium presentation, Jaya Biosciences’ scientific founder and science advisory board chair, Professor Mark Sands, reported on recently updated human genetic analyses suggesting that heterozygous loss-of-function mutations in lysosomal enzyme genes are enriched in Alzheimer’s disease (AD) patients. This new analysis generated from a much larger whole genome sequence database confirmed their previous human genetic findings from a smaller whole exome database. Professor Sands presented in vivo data that validated several of the genes identified in the human AD cases and identified two additional lysosomal enzyme genes that affect amyloid-beta (Aβ) processing in heterozygous animals. Finally, CNS-directed, AAV-mediated gene therapy with JB111 (the Company’s lead therapy) was shown to ameliorate the biochemical, histological, and clinical signs of disease in an animal model of PPT1-associated AD (5xFAD harboring a heterozygous mutation in the PPT1 gene).
“We are pleased to see that the additional genetic analyses corroborated our initial findings of lysosomal dysfunction in Alzheimer’s disease,” said Pawel Krysiak, President and CEO of JayaBio. “The updated preclinical data we presented continue to show the high potential of targeting PPT1 haploinsufficiency in Alzheimer’s and support the necessity for a paradigm shift in the strategy for AD therapy development. Our team is committed to further advancing JayaBio’s platform targeting the upstream effector lysosomal pathway in an effort to address an enormous unmet need in neurodegenerative diseases.”
The following talk was presented at the at the 45th SIMD Annual Meeting:
Title: Haploinsufficiency of lysosomal enzymes and Alzheimer’s disease
Date and Time: Mon, April 15th, 2024 at 5:00 PM ET
Session: Science Session 4
Presenter (In-person): Prof. Mark Sands, Washington University School of Medicine, St. Louis, MO
Human genetic analysis suggests that heterozygous loss-of-function mutations in lysosomal enzyme genes are enriched in Alzheimer’s patients.
Heterozygosity of five different lysosomal enzyme genes (PPT1, NAGLU, GALC, IDUA, GUSB) significantly affects amyloid precursor protein (APP) processing and favors pro-amyloidogenic pathway.
PPT1 haploinsufficiency greatly exacerbates Aβ plaque formation and significantly reduces the life span of the 5xFAD mouse model of AD.
CNS-directed, AAV-mediated PPT1 gene therapy significantly increases the life span of 5xFAD/PPT1+/- mice.
“The updated human genetic data confirmed that heterozygous deleterious mutations in a subset of lysosomal genes are enriched in patients with Alzheimer’s disease,” said Prof. Mark Sands. “Together with previously reported gene dosage effects of these mutations on Aβ processing, it underscores the utility of targeting lysosomal genes haploinsuficiencies in neurodegenerative diseases and adds to the evolving understanding regarding the status of lysosomal enzyme gene defects carriers. Especially considering that our lead therapy, the CNS-directed AAV-mediated PPT1 gene therapy, dramatically improved the clinical signs in a mouse model of AD.”
“We continue to be encouraged by the positive preclinical results from our JB111 gene therapy study in PPT1-associated Alzheimer’s model and look forward to translating our strong animal proof of concept to IND-enabling toxicology and clinical studies,” added Dr. Neal Goodwin, Co-founder and Chief Scientific Officer of JayaBio.
For more information about the 45th SIMD Annual Meeting, please go to SIMD2024 Meeting. The abstract will also be made available on JayaBio’s corporate website.
About Autophagy-Lysosomal Pathway in Neurodegeneration
Lysosomes are subcellular organelles responsible for the normal degradation and turnover of cellular components and aggregation-prone proteins. Deficits in the autophagy-lysosomal pathway (ALP) result in protein aggregation, the generation of toxic protein species, and accumulation of dysfunctional organelles, which are hallmarks of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD).1 Lysosomal degradation plays a critical role, as the degradation of autophagosomal cargo cannot proceed without successful fusion to an available and functional lysosome.2 Lysosomal function declines with age and likely contributes both to the aging process itself as well as the development of age-related diseases such as neurodegenerative diseases and cancer.2,3 Emerging evidence suggest that defects in certain lysosomal enzyme genes are associated with various neurodegenerative diseases such as Parkinson’s Disease4, Frontotemporal Dementia5, and Alzheimer’s Disease.6
1. Martini-Stoica H, et al., (2016) Trends Neurosci 39(4):221-234
2. Levine B, Kroemer G, (2019) Cell 176(1-2):11-42
3. Hansen M, et. al., (2018) Nature Rev Mol Cell Biol, 19(9):579-593
4. Sidransky E, et al., (2009) N Engl J Med 361(17):1651-61.
5. Baker M, et al., (2006) Nature, 442(7105):916-9
6. Lopergolo D, et al., (2023) J Med Genet, Epub ahead of print
About JB111
JB111, Jaya Biosciences’ lead therapy, is an experimental CNS-directed AAV9-mediated PPT1 gene therapy currently being developed for neurodegeneration associated with PPT1 haploinsufficiency (carrier status for loss-of-function mutations in palmitoyl protein thioesterase-1 gene or PPT1 heterozygosity). JB111 showed very promising results in the animal model of PPT1-associated Alzheimer’s disease (5XFAD mouse harboring PPT1 heterozygous allele). Single intracerebroventricular (ICV) injection of JB111 resulted in a significantly increased life span and improved cognitive performance.
About Jaya Biosciences, Inc.
Jaya Biosciences is a privately held pre-clinical stage life sciences company developing CNS-directed gene therapies for genetically defined neurodegenerative diseases, including Alzheimer's, Parkinson’s, and frontotemporal dementia. Jaya’s platform is based on the groundbreaking discovery that carriers of loss-of-function mutations in genes for lysosomal enzymes have an increased risk of neurodegeneration, including early onset of symptoms. Jaya Biosciences’ team, proven in drug development and commercialization of lysosomal targets and gene therapies, is dedicated to addressing unmet needs in neurodegeneration and adding value to patient and medical communities worldwide. Jaya’s mission is to fulfill a promise of victory over neurodegeneration by identifying and targeting the relevant pathways involved in the etiology of these debilitating diseases. For more information, please visit www.jayabio.com
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Jaya Biosciences Inc.